Continuing Education

Hypoactive sexual desire disorder: How do you identify it and treat it?

Approximately 1 in 10 women has distressing low sex drive, otherwise known as hypoactive sexual desire disorder (HSDD). How do healthcare providers determine whether a given patient has HSDD? And how should they treat it? The authors address these challenges in this article.

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Clinical management of dilemmas in contraception

In most cases, prescribing contraceptives and managing the care of women using them is straightforward. But sometimes, because of a woman’s health history or changing health status or because of the occurrence of an unforeseen event, a management dilemma arises. The author discusses three dilemmas in contraception and options for managing them. In addition, he provides background information about the evidence-based guidelines that should inform healthcare providers’ decisions about which contraceptives should or should not be prescribed for individual women and discusses contraceptive options that are newly available or on the horizon.

The provision of high-quality contraceptive services is supported by three benchmark, evidence-based clinical practice guidelines developed by the CDC. The U.S. Medical Eligibility Criteria for Contraceptive Use, 2016B, known as the USMEC, provides recommendations on contraceptive safety, particularly for women with chronic diseases.1  The USMEC provides a safety rating for more than 60 conditions in categories of contraceptives such as combined hormonal contraceptives (CHCs), which include combined oral contraceptives (COCs), the contraceptive patch, and the contraceptive vaginal ring; progestin-only contraceptives (POCs), which include depot medroxyprogesterone acetate (DMPA), progestin-only implants, and progestin-only pills (POPs); and intrauterine devices (IUDs) such as the levonorgestrel intrauterine system (LNG-IUS) and the copper IUD (Cu-IUD). In addition, safety information is provided for emergency contraceptives (ECs), barrier methods, fertility awareness-based methods (FABMs), lactational amenorrhea, withdrawal, and sterilization. The safety categories are numbered 1 through 4 as follows:
1. No restriction for the use of a given contraceptive method; the method can be used safely.
2. Advantages of using the method generally outweigh the theoretical or proven risks; the method can generally be used safely, but more than the usual follow-up is needed.
3. Theoretical or proven risks usually outweigh the advantages of using the method; clinical judgment should determine whether the given method can be used safely in a particular woman. In these cases, use of the contraceptive method, particularly one that is highly effective, will be safer than an unintended pregnancy
4. Unacceptable health risk if the contraceptive method is used; do not use the method.

The second guideline, the U.S. Selected Practice Recommendations for Contraceptive UseC, known as the SPR, offers information and recommendations that focus on contraceptive efficacy, rules for use, and management of side effects.2 Of note, the CDC has created an app that combines all the recommendations in both the USMEC and the SPR. The easy-to-use app is downloadable for free at the Apple Store or the Google Play Store by typing CDC Contraception in the search box. All healthcare providers (HCPs) who provide contraceptive services are strongly encouraged to download the app, become familiar with its use, and use it frequently when making contraceptive decisions.

The third guideline, Providing Quality Family Planning Services, 2014D, known as the QFP, which was developed jointly by the U.S. Office of Population Affairs and the CDC, is a resource that fills in the gaps on family planning topics not included in the USMEC or SPR.3 These topics include contraceptive counseling, pregnancy testing and options counseling, achieving pregnancy, basic infertility, preconception health, and preventive health screening for women and men.

Two of the three aforementioned guidelines, the USMEC and the SPR, were updates to the 2012 versions. The updates in these 2016 publications were based on the publication of important new studies, as well as on changes to the World Health Organization (WHO) MEC and SPR recommendations. In the USMEC, safety categories were lowered or raised for several conditions, especially the use of CHCs in women with migraine headaches and the use of POCs in lactating women. Several conditions were included for the first time (e.g., cystic fibrosis, multiple sclerosis) and certain drug–drug interactions were updated (e.g., selective serotonin reuptake inhibitors and St. John’s wort; hormonal methods in women using antiretrovirals for HIV infection). The most important modification to the USMEC was the inclusion of ulipristal acetate (UPA) in the EC section.1 An important update to the SPR is advising a woman to start or resume hormonal contraception no sooner than 5 days after use of UPA.2

Dilemma #1: Use of hormonal contraceptives and breastfeeding

Judy is a 30-year-old woman who experienced an uncomplicated vaginal birth at 37 weeks. Her newborn daughter weighed 2,704 g and is healthy. Judy plans to fully breastfeed her infant and requests a prescription for contraception before discharge on postpartum day 2. She is not interested in an IUD at this time. Which hormonal methods are safe for her to use? When can she safely start using the method chosen?

Combined hormonal contraceptives
Judy and her HCP discuss the pros and cons of CHCs, which include the pill, the patch, and the ring.

Effect on lactation

Among CHCs, COCs have been studied the most with respect to safety of use in lactating mothers and their infants. COCs have been found to have no effect on the quality (content) of breast milk in terms of its amounts of protein, fat, iron, and copper. In terms of the quantity of breast milk, studies conducted in the 1960s and 1970s showed that women who initiated COCs containing high-dose estrogen before the establishment of lactation had a reduced quantity of breast milk.4 By contrast, more recent studies have shown that women who initiated COCs containing low-dose estrogen after lactation was established had minimal, if any, changes in breast milk quantity.5 Nevertheless, concern about the adverse effect of CHCs on breast milk supply still exists—especially in the context of women having difficulty with breastfeeding their newborn for a variety of reasons.

Use of COCs appears to influence the duration of breastfeeding. One early study showed that COC users breastfed for an average of 3.7 months, versus an average of 4.6 months for women who did not use COCs.6 However, a 2016 updated systematic review of 15 RCTs and cohort studies showed an inconsistent impact of COCs on breastfeeding duration and success.7

Neonatal risk
Research has shown that the ethinyl estradiol dose reaching newborns via COC users’ breast milk is similar to the amount they would receive from the mother’s daily ovarian estradiol production. Furthermore, studies have shown no effect of COCs on breastfed infants’ development, including neurologic development and growth rates.7

Maternal risk
Changes in maternal clotting factors persist for up to 6 weeks after childbirth, resulting in an increased risk for venous thromboembolism (VTE) over this time period. Use of CHCs in this setting of increased hypercoagulability could potentially increase VTE risk even more. Given the fact that lactating women rarely ovulate in the first 6 weeks after delivery, the risk of using a CHC far outweighs the benefit because the likelihood of ovulation is so low. As a consequence, the USMEC risk categories are 4 for women <21 days postpartum; 3 for those 21-29 days postpartum, with or without other VTE risk factors* or 30 42 days postpartum with other VTE risk factors*; 2 for those 30-42 days postpartum with no other VTE risk factors; and 1 for those >42 days postpartum.1

Progestin-only contraceptives
Unlike CHCs, POCs have no effect on the quality or quantity of breast milk.8,9 Greater VTE risks are not expected with POCs because they do not affect Packages of oral contraceptivesclotting factors.10 The CDC commissioned a systematic review of 47 studies to assess the effects of POCs when used by lactating women.11 The evidence failed to demonstrate adverse breastfeeding outcomes or health outcomes in infants whose mothers took POCs. USMEC risk categories for lactating women who use POPs (those available in the United States contain norethindrone), DMPA, or the etonogestrel implant are 2 during postpartum days 1-29 and 1 for postpartum day 30 onward.1

General comments
Discussions about contraceptive use by lactating women should consider each woman’s desire to breastfeed, her risk for breastfeeding difficulties, and her risk for unintended pregnancy.1 The following clarification was added to the 2016 USMEC regarding progestin-only methods: “Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.”

The Academy of Breast-Feeding Medicine has a different take on the use of hormonal contraceptives in breastfeeding women. According to Clinical Protocol #13, HCPs should inform women that CHCs may decrease milk supply, especially in the early postpartum period.12 Hormonal methods should be discouraged in any of these settings: existing low milk supply or history of lactation failure, history of breast surgery, multiple births, preterm birth, or compromised health of mother and/or infant.

Because Judy chooses to breastfeed exclusively, she is highly unlikely to become pregnant in the first 6 weeks postpartum. She wants the many health benefits of long-term breastfeeding that will accrue to both her infant and herself. During this time, she is at significantly increased risk for VTE and should avoid any of the CHCs. If she is fully breastfeeding (no additional nutrition for her newborn), she can rely on lactational amenorrhea as her contraceptive method for at least 12 weeks postpartum, and even longer (but no more than 6 months) if she remains amenorrheic. If she insists on starting a method before leaving the hospital, POPs, DMPA, or a contraceptive implant are all good options—as long as she is reminded to return for advice on another method if she has difficulties with breastfeeding.

*VTE risk factors include age ≥35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, body mass index >30 kg/m2, postpartum hemorrhage, post-caesarean delivery, and pre-eclampsia or smoking.

Dilemma #2: Initiation of hormonal contraceptives after use of ulipristalacetate

Mary Ann is a 25-year-old woman presenting with a request for an EC. She had unprotected intercourse (UPI) with a new partner 4 days ago, on day 10 of her usual 30-day cycle. In addition, she wants to start a method of contraception as soon as possible. Weighing 200 pounds and standing 5 feet, 4 inches, she has a BMI of 34 kg/ m2, placing her in the obese category. What should be done for Mary Ann in terms of her immediate need for an EC and her long-term need for birth control?

Emergency contraceptives available
The single-dose levonorgestrel (LNG) tablet (1.5 mg) is labeled for use within 72 hours of UPI. Its efficacy in preventing pregnancy is good when taken 0-72 hours following UPI and moderate when taken 72-120 hours following UPI. LNG-containing EC products available in the U.S. include Plan B One-Step® and multiple generic one-dose tablets. No physical assessment is required prior to use; in fact, single-dose LNG is widely available without a prescription in pharmacies across the country.

The next option is ulipristal acetate or UPA (Ella®), which prevents ovulation, even with follicles up to 18-20 mm. UPA is taken orally in a single 30-mg dose and is labeled for use up to 5 days after the last UPI. In a meta-analysis of the efficacy of UPA versus LNG, given 0-72 hours following the last UPI, 22 pregnancies occurred in 1,617 women in the UPA group (1.4%) versus 35 pregnancies in 1,625 women in the LNG group (2.2%) (odds ratio, 0.58, 0.33-0.99; P = 0.046).13

The third option—of note, this use is off label—is the copper intrauterine device, which has an EC failure rate of 0.1%.14 This device can be inserted within 5 days after UPI. Women in whom the Cu-IUD is used as an EC can continue using it as a regular contraceptive. A study of Chinese women by Wu et al.15 showed the 12-month post-insertion continuation rate was 94.0 per 100 woman-years. Sanders et al.16 found that the 1-year continuation rate for the Cu-IUD, when initiated as EC, was 60%. The LNG-IUS is still being studied as an EC and cannot yet be recommended for this indication.

Efficacy of ECs in overweight/ obese women
The aforementioned meta-analysis comparing the effects of LNG and UPA as ECs showed that, relative to women of normal weight (BMI <25), overweight women (BMI, 25-30) and obese women (BMI ≥30) had pregnancy rates that were 1.5 times greater and >3 times greater, respectively.16,17 For obese women, the risk was significantly greater for those taking LNG than for those taking UPA. Two studies have shown that absorption of the hormones used in COCs is slower in obese women than it is in women of normal weight.18,19 With ECs, immediate absorption is important; this delay could explain the lower efficacy in obese women.20

In terms of Mary Ann’s immediate need for an EC, she is advised that the Cu-IUD would be much more effective in preventing pregnancy than either oral EC product. Mary Ann decides to have the Cu-IUD inserted right away and keeps it as her birth-control method. Had she not chosen the Cu-IUD, it would have been reasonable to offer her UPA because its efficacy in women in this weight category is better than using no method of EC. In her case, using oral LNG EC would have been no better than using a placebo.

Starting hormonal contraception after receiving ulipristal
For women who are better candidates than Mary Ann for UPA, the following information is important to know. UPA is a selective progesterone-receptor (PR) modulator that blocks the effect of progesterone at many sites. Despite the proven efficacy of this EC method, there was concern that starting a progestin-containing contraceptive immediately after taking UPA would displace UPA from PRs, thereby reducing UPA’s effectiveness. Sure enough, a small pharmacodynamic study showed that initiating a desogestrel (DSG)-containing POP the day after UPA administration significantly reduced the ovulation-delaying effect of UPA.21 In this study, whereas ovulation occurred in only 1 (3%) of 29 UPA-only cycles in the first 5 days, it occurred in 13 (45%) of 29 UPA+DSG cycles. These results prompted a change in the product labeling for Ella22: After using this product, if a woman wants to use hormonal contraception, she should do so no sooner than 5 days after UPA administration. If she has sexual intercourse, she should use a reliable barrier method until her next menstrual period.

Dilemma #3: Management of a lost intrauterine device string

Rosa is a 45-year-old G3P3 who had an IUD inserted 8 years previously. She remembers that it had a T shape but is unsure which type of IUD it is. She reports that she has been unable to feel the string for the past 2 months; before that time, she checked for it sporadically. A speculum examination confirms that no string is present at the external cervical os.

Whenever an HCP encounters a patient with a “missing” IUD string, four possibilities should come to mind: (1) The IUD is in situ, with the string coiled in the cervical canal or endometrial cavity or simply cut short, broken, or severed; (2) The woman has an intrauterine pregnancy, with the IUD string pulled up into the expanding uterine cavity; (3) Asymptomatic expulsion has occurred; or (4) In the unlikely event that the uterus was perforated when the IUD was placed, the string may not be visible because the IUD is embedded in the myometrium or translocated through the uterine wall and into the abdominal cavity.

Recommended steps in management
Before performing any intervention, the first step in management of a lost string is to perform an office pregnancy test. If the result is positive, the pregnancy must be located and dated (see subsection on Pregnancy in next section). If the result is negative, the HCP can probe the cervical canal with an endocervical brush, using a spinning motion to catch the string. (This step is taken next because it is assumed, albeit not yet confirmed, that the IUD is in situ and that the HCP wants to position the string so that the woman can find it the next time she checks for it.) If this maneuver is not effective, the HCP can ask the woman whether she wants to keep the IUD—if it is found to be in the correct position—or if she prefers to have it removed.

If the woman wants to keep using the IUD, and it has not expired, the next step is performance of a pelvic ultrasound, either in the office or in a diagnostic imaging center. If the IUD is identified as being in situ, it can remain in place until the expiration date or until the woman has problems with it or wants to become pregnant. If the IUD is not identified in the uterine cavity, the next step is performance of a kidney/ureter/bladder x-ray (KUB) to determine whether it is outside the uterus but in the abdominal cavity. If so, a translocation is diagnosed. If an IUD is not seen on the pelvic ultrasound or the KUB, then expulsion is diagnosed. These steps can be performed in a single visit by ordering a pelvic ultrasound first and authorizing an immediate KUB if the IUD is not identified.

If the patient wants the IUD removed, extraction can be attempted in the office, but only by an HCP experienced in performing intrauterine procedures. A plastic IUD thread retriever is now available in the U.S.; its use is relatively noninvasive. As an alternative, an alligator forceps can be used to search within the uterine cavity—using a tenaculum to stabilize the uterus before intrauterine manipulation.23 Simultaneous real-time abdominal ultrasound, if available, is helpful in guiding the tip of the instrument used for extraction to the location of the IUD within the endometrial cavity; one study with this technique showed a 97% success rate.24

If an IUD frame or string cannot be grasped or otherwise detected by feel in the cavity, a combination of pelvic ultrasound and a KUB, as described earlier, should be ordered. In this case, the likelihood of asymptomatic expulsion is high, but deep embedment or translocation is possible. If the IUD is grasped but cannot be removed, it likely is embedded, in which case 3D ultrasound or computed tomography (CT) of the pelvis can suggest whether a hysteroscopic or laparoscopic approach is more likely to be successful. Under ideal circumstances, these imaging tests are ordered by the OB/GYN physician who will perform the extraction in the surgical center or operating room, depending on preference, in order to avoid duplication of an expensive imaging procedure.

More information about “missing” string possibilities 2, 3, and 4 Pregnancy with IUD
If the woman’s office pregnancy test result is positive, pelvic ultrasound is used to determine the site of the pregnancy. If it is ectopic, the woman should be referred immediately to an OB/GYN physician for medical or surgical treatment of the ectopic pregnancy. If it is intrauterine and viable, the woman needs to know that the risks of adverse pregnancy outcomes are greater in the setting of IUD retention than if it were to be removed.25 Removal is recommended when the strings are visible or when the device can be removed safely from the cervical canal. If pregnancy termination is planned, then the IUD can be removed during a surgical abortion or before a medication abortion.

If the woman decides to continue an intrauterine pregnancy and the IUD strings are not visible, the HCP should not attempt removal. Instead the HCP should counsel the woman regarding the increased risks of spontaneous abortion, septic abortion, chorioamnionitis, and preterm delivery. The woman should undergo increased surveillance during antenatal care. Because the IUD is outside the amniotic sac, the fetus is not at greater risk for birth defects. Insufficient evidence exists regarding adverse fetal effects of small exposure to LNG during gestation.25

Expulsion of IUD
Expulsion of the IUD occurs in 2% of insertions within the first year. Risk of expulsion is related to the HCP’s skill at fundal placement; the woman’s age, parity, and uterine configuration; time since insertion (increased risk within the first 6 months), and timing of insertion (menses, postpartum, post-abortion); for example the risk is greater if the device is inserted within 48 hours of childbirth.26 A woman with an unnoticed expulsion may present with pregnancy. A woman with a partial expulsion may present with pelvic pain, cramps, or intermenstrual bleeding or she may mention that the IUD string is longer than she previously perceived.26

Perforation leading to translocation or embedment
The overall incidence of uterine perforation as a result of IUD insertion is about 0.1%,27 although the rate is significantly higher— 0.6%—in postpartum women. Depending on how the IUD is positioned and where it has translocated, it is removed via hysteroscopy or laparoscopy. Because the Cu-IUD, compared with the LNG-IUS, can cause greater inflammation and more adhesions, it must be extracted promptly via laparoscopy. The LNG-IUS is less reactive, but most experts recommend laparoscopic removal as well. If advanced imaging such as 3D ultrasound or CT of the pelvis shows that the IUD is embedded in the myometrium, it usually can be removed hysteroscopically. However, if imaging shows that none of the IUD frame is accessible in the endometrium and most of the device protrudes through the myometrium and into the abdominal cavity, laparoscopic removal is indicated.

A pelvic ultrasound shows that Rosa’s IUD is properly situated in the uterine cavity. Because the device is identified as an LNG-IUS that was inserted 8 years earlier, she and her HCP decide that it should be removed and replaced. The first procedure is accomplished in the office with an alligator forceps with simultaneous ultrasound and the old device is replaced by a new one.

Newly approved contraceptives
The FDA approved two new contraceptive products in 2018.

AnnoveraTM CVR (contraceptive vaginal ring) This ring containing segesterone acetate and ethinyl estradiol prevents ovulation for 1 year (13 cycles). The woman inserts it into the vagina herself, leaves it in place for 21 days, and then removes it for 7 days to allow a withdrawal bleed. The ring can be removed over the 21-day period for intercourse and cleaning, but not for longer than 2 hours. This product is like NuvaRing® with respect to the amount of progestin and estrogen released and the diameter, but Annovera is twice as thick (8.4 mm vs. 4 mm) because each ring is used for 13 cycles, not 1 cycle. According to the manufacturer, Annovera CVR is the “first woman-controlled, procedure-free, long-acting, reversible birth control product.” It is longer acting than other methods, but because it does need to be removed and tended periodically, unlike the IUD and implant, which are “forgettable,” it does not qualify as being a true long-acting reversible contraceptive method.

Natural Cycles® app This FABM is the first and only fertility monitoring app with FDA approval to be marketed as a contraceptive. It can be used for either contraception or timing intercourse to become pregnant. With respect to its mechanism of action, it relies on cycle pattern and basal body temperature, not cervical mucus. Use of the app requires the use of a special basal body temperature thermometer that signals the smartphone with the temperature reading. The app factors in current basal body temperature and a woman’s past menstrual and monitoring history in predicting future ovulatory events so that she knows when she can engage in, or avoid, intercourse. Compared with other FABMs, this app has these advantages: It has withstood FDA scrutiny, it integrates objective data about prior ovulation patterns, it requires minimal user intervention, and it has a clear user interface. However, relative to other FABMs, its failure rate is similar and it requires disciplined use by both partners. To minimize contraceptive failure, this app is best used with a barrier method on “red” days.

On the horizon

For decades, contraceptives have been prescribed by HCPs and furnished by clinics or pharmacies. Newer alternatives include having registered nurses or pharmacists prescribe and furnish CHCs via standing orders. But the “delivery system” of the future—and, by the way, the future is here—involves provision of CHCs via telehealth or apps, including NurxE, PRJKT RUBYF, MavenG, virtuwell.comH, pandia healthI, Pill ClubJ, and LemonaidK. The lattermost five apps offer a Skype-like interaction with a nurse practitioner or other clinician. The app Planned Parenthood DirectL is usable in about half the states in the U.S.

One day soon, in a strange counterpoint to storks delivering babies, drones may be delivering pills, patches, and rings to whoever orders them.

References

1. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(3):1-103. cdc.gov/mmwr/ volumes/65/rr/pdfs/rr6503.pdf
2. Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(4):1-66. cdc.gov/mmwr/ volumes/65/rr/pdfs/rr6504.pdf
3. Gavin L, Moskosky S, Carter M, et al. Providing Quality Family Planning Services: Recommendations of CDC and the U.S. Office of Population Affairs. MMWR Recomm Rep. 2014;63(4):1-54. cdc.gov/mmwr/pdf/rr/rr6304.pdf
4. Effects of hormonal contraceptives on breast milk composition and infant growth. World Health Organization (WHO) Task Force on Oral Contraceptives. Stud Fam Plann. 1988;19(6 pt 1):361-369.
5. Espey E, Ogburn T, Leeman L, et al. Effect of progestin compared with combined oral contraceptive pills on lactation: a randomized controlled trial. Obstet Gynecol. 2012;119(1):5-13.
6. Nilsson S, Nygren KG, Johansson ED. d-Norgestrel concentrations in maternal plasma, milk, and child plasma during administration of oral contraceptives to nursing women. Am J Obstet Gynecol. 1977;129(2):178-184.
7. Tepper NK, Phillips SJ, Kapp N. et al. Combined hormonal contraceptive use among breastfeeding women: an updated systematic review. Contraception. 2016;94(3):262-274.
8. Truitt ST, Fraser AB, Grimes DA, et al. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation. Cochrane Database Syst Rev. 2003;(2):CD003988.
9. Lopez LM1, Grey TW, Stuebe AM, et al. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation. Cochrane Database Syst Rev. 2015;(3):CD003988.
10. Sitruk-Ware R. Hormonal contraception and thrombosis. Fertil Steril. 2016;106(6):1289-1294.
11. Phillips SJ, Tepper NK, Kapp N, et al. Progestogen-only contraceptive use among breastfeeding women: a systematic review. Contraception. 2016;94(3):226-252.
12 Berens P, Labbok M; Academy of Breastfeeding Medicine. ABM Clinical Protocol #13: Contraception During Breastfeeding, Revised 2015. Breastfeed Med. 2015;10(1):3-12. abm.memberclicks.net/assets/DOCUMENTS/ PROTOCOLS/13-contraception-and-breastfeeding-protocol-english.pdf
13. Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet. 2010;375(9714):555-562.
14. Cleland K, Haoping Z, Goldstuck N, et al. The efficacy of intrauterine devices for emergency contraception: a systemic review of 35 years of experience. Hum Reprod. 2012;27(7):1994-2000.
15. Wu S, Godfrey EM, Wojdyla D, et al. Copper T380A intrauterine device for emergency contraception: a prospective, multicentre, cohort clinical trial. BJOG. 2010;117(10):1205-1210.
16. Sanders JN, Turok DK, Royer PA, et al. One-year continuation of copper or levonorgestrel intrauterine devices initiated at the time of emergency contraception. Contraception. 2017;96(2):99-105.
17. Glasier A, Cameron ST, Blithe D, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception. 2011;84(4):363-367.
18. Edelman AB, Cherala G, Stanczyk FZ. Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review. Contraception. 2010;82(4):314-323.
19. Westhoff CT, Torgal AL, Mayeda ER, et al. Ovarian suppression in normal-weight and obese women during oral contraceptive use. Obstet Gynecol. 2010;116(2 pt 2):275-283.
20. Rapkin RB, Creinin MD. Update: When it comes to the morning-after pill, physicians need a wake-up call. OBG Manage. 2011;23(8):16-24.
21. Brache V, Cochon L, Duijkers IJ, et al. A prospective, randomized, pharmacodynamic study of quick-starting a desogestrel progestin-only pill following ulipristal acetate for emergency contraception. Hum Reprod. 2015;30(12):2785-2793.
22. Ella prescribing information. Last updated June 2018. dailymed.nlm.nih.gov/dailymed/ drugInfo.cfm?setid=052bfe45c485-49e5-8fc4-51990b2efba4#LINK_94c46528-93c6-49a5aef1-3597044978d2
23. Prabhakaran S, Chuang A. In-office retrieval of intrauterine contraceptive devices with missing strings. Contraception. 2011;83(2):102-106.
24. Kottmann C, Troncoso M, Valenzuela I, et al. Ultrasound-guided extraction of intrauterine devices with nonvisible threads: 254 consecutive cases: an effective, noninvasive technique. J Ultrasound Med. 2019 Mar 18. Epub ahead of print.
25. Brahmi D, Steenland MW, Renner RM, et al. Pregnancy outcomes with an IUD in situ: a systematic review. Contraception. 2012;85(2):131-139.
26. World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 2nd ed. Geneva, Switzerland: WHO; 2000.
27. Rowlands S, Oloto E, Horwell DH.Intrauterine devices and risk of uterine perforation: current perspectives. Open Access J Contracept. 2016;7:19-32. ncbi.nlm.nih. gov/pmc/articles/PMC5683155/

Continuing Education: Insomnia across the lifespan

Healthcare providers (HCPs) caring for women of any age will find that a substantial proportion of them have difficulty falling and/or staying asleep. When insomnia interferes with their daily life and causes distress, they may seek professional help. This article provides background information about sleep, and offers HCPs useful and up-to-date information regarding the evaluation of patients presenting with sleep problems and the wide variety of treatments that are available.

Continue reading »

Treatment of decreased sexual desire in women

About a third of women in the United States experience decreased sexual desire (DSD), a symptom that may be part of a more complex diagnosis. The author discusses DSD with respect to background information, screening, and diagnosis, and then focuses on treatment of this common, oftentimes perplexing, problem. Continue reading »

The ABCDs of bacterial vaginosis: Abnormal flora, Bothersome symptoms, Chronicity, and Differential diagnosis

Faculty:

Alisa Pascale, DNP, WHNP-BC, is a women’s health nurse practitioner at the Vulvovaginal Disorders Program & Gynecology at Massachusetts General Hospital and Clinical Instructor at MGH Institute of Health Professions, both in Boston, Massachusetts.

Intended audience: This continuing education (CE) activity has been designed to meet the educational needs of nurse practitioners who provide care for women of any age.

CE approval period: Now through December 31, 2019

Estimated time to complete this activity: 1 hour CE approval hours: 1.0 contact hours, including 0.5 contact hours of pharmacology credit (NCC code 2A)

Goal statement: To understand the abnormal vaginal ecosystem in women prone to bacterial vaginosis (BV) and to use current evidence and guidelines in treating single episodes of BV and in reducing chronic/recurrent episodes of BV. Continue reading »

Managing women’s health issues across a lifespan: NPWH 2017-2018 regional meetings

Before reading the article, click here to take the pretest.

Over the past year, NPWH sponsored four regional meetings highlighting updates on the management of women’s health issues across a lifespan. The meetings were presented to live audiences using an interactive learning strategy, with several clinical scenarios illustrating issues within four topic areas: contraception, bacterial vaginosis, hypoactive sexual desire disorder, and postmenopausal osteoporosis. The author of this article has chosen one scenario for each topic to demonstrate how this learning strategy can cover important health areas in a way that intrigues and challenges, in this case, our readers. Continue reading »

Managing postmenopausal dyspareunia: An update

Faculty:

Susan Hoffstetter, PhD, WHNP-BC, FAANP, is a professor at Saint Louis University School of Medicine, Department of Obstetrics, Gynecology & Women’s Health, Division of Uro-Gynecology, in St. Louis, Missouri.

Intended audience: This continuing education (CE) activity has been designed to meet the educational needs of nurse practitioners who provide care for menopausal and postmenopausal women. Continue reading »

Dense breasts: Cancer risk and supplemental imaging modalities

By Mary Ellen Egger, APN, WHNP, CBPN and Diana L. Lam, MD

Faculty:

Mary Ellen Egger, APN, WHNP, CBPN, is a nurse practitioner in the Breast Center at Vanderbilt University in Nashville, Tennessee.

Diana L. Lam, MD, is an Assistant Professor in the Department of Radiology specializing in Breast Imaging at the University of Washington, Seattle Cancer Care Alliance, in Seattle, Washington.

Intended audience: This continuing education (CE) activity has been designed to meet the educational needs of nurse practitioners who provide care for women in any age bracket. Continue reading »

BRCA and beyond: The contribution of genetics to breast and gynecologic cancers (Part 2)

Faculty

Kate McReynolds, APRN, MSc, MSN, ANP-BC, AGN-BC, is a Genetic Nurse Practitioner at Vanderbilt University Medical Center in Nashville, Tennessee.

Intended audience

This continuing education (CE) activity has been designed to meet the educational needs of nurse practitioners who provide care for women in any age bracket.

CE approval period

Now through November 30, 2018

Estimated time to complete this activity

1 hour

CE approval hours

1.0 contact hour of CE credit

Needs assessment

This two-part article focuses on hereditary cancer syndromes associated with breast and gynecologic cancers. In part 1, the author provided background information about hereditary cancer, detailed several specific hereditary breast and gynecologic cancer syndromes (HBGCSs), and explained the gene alterations involved in these syndromes. In part 2, the author describes ways that healthcare providers can identify women who may have one of the two most common syndromes and who could therefore benefit from genetic risk assessment, counseling, and testing—processes she also discusses. The author also explains how to interpret genetic test results and provides management recommendations for the two most common HBGCSs. Continue reading »

BRCA and beyond: The contribution of genetics to breast and gynecologic cancers (Part 1) 

BRCA and beyond: The contribution of genetics to breast and gynecologic cancers (Part 1)Faculty
Kate McReynolds, APRN, MSc, MSN, ANP-BC, AGN-BC, is a Genetic Nurse Practitioner at Vanderbilt University Medical Center in Nashville, Tennessee.

Intended audience
This continuing education (CE) activity has been designed to meet the educational needs of nurse practitioners who provide care for women in any age bracket.

CE approval period
Now through September 30, 2018 Continue reading »

Practical strategies for the diagnosis and management of binge eating disorder

Binge eating disorder (BED), now included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),1 is defined as follows:

  • Recurrent and persistent episodes of binge eating
  • Binge eating episodes that are associated with three (or more) of the following:
    • Eating much more rapidly than normal
    • Eating until feeling uncomfortably full
    • Eating large amounts of food when not feeling physically hungry
    • Eating alone because of being embarrassed by how much one is eating
    • Feeling disgusted with oneself, depressed, or very guilty after overeating
  • Marked distress regarding binge eating
  • Absence of regular compensatory behaviors (such as purging)

Particularly common among females (See Cases 1, 2, and 3) and associated with obesity, BED poses physical, psychological, and social challenges that decrease health-
related quality of life (HRQOL) and increase disease burden.

Etiology

The etiology of BED is multifactorial and complex. Although associated with hedonic hunger, BED is linked less to pleasure and more to an attempt to suppress negative feelings through bingeing without purging.2 Motivation to binge likely also arises from homeostatic hunger.

Risk factors

Risk factors for BED include genetics, female gender, Caucasian ethnicity, weight concern, negative body image, childhood problems, low self-esteem and self-efficacy, low family cohesion, psychiatric morbidity, and stressful events.3,4 In addition, a community-based case–control study demonstrated that patients with BED, versus controls, were significantly more likely to report sexual abuse and repeated severe physical abuse. The typical overweight person with BED is overly concerned with body shape and weight. BED is most likely to occur in young women of high socioeconomic status in industrialized countries, but it is not limited to this population (See Cases 1, 2, and 3).

Binge-eating disorder in children and adolescents

In children and adolescents, early identification and treatment of BED is vital (See Case 1). Loss of control over eating is associated with modifiable lifestyle factors. Often considered temporary, BED is actually a long-term chronic condition often associated with co-morbid obesity. Childhood factors that increase risk for BED include obesity, self-criticism, poor self-esteem, body dissatisfaction, and emotional abuse.5 In female adolescents and young adult women, BED is associated with pre-existing depressive symptoms and an increased risk for developing mood disorders.6

Specific goals of treatment for children and adolescents include treatment of underlying depression or anxiety, improvement of self-esteem, normalization of eating patterns, promotion of physical activity, and implementation of family therapy to address family dysfunction and engage family members in supporting the patient’s recovery. BED treatment outcomes can be optimized through early detection and referral to eating disorder specialists; incorporating a multidisciplinary treatment team to address the physical, psychological, nutritional, and spiritual aspects of BED; and combining cognitive behavioral therapy (CBT), a self-help program, and, when appropriate, pharmacotherapy.

Co-morbid psychiatric disorders

Co-morbid anxiety, mood, and disruptive behavior disorders are common in patients with BED, as are obsessive-compulsive disorder, post-traumatic stress disorder, and substance abuse. Co-morbid obesity increases psychopathology, emotional eating, concerns about weight and body shape,7 and perhaps a desire for bari­atric surgery.8 Obesity and BED are common in patients with bipolar disorder. In patients with personality disorders, alexithy­mia (a personality construct characterized by the subclinical inability to identify and describe emotions in the self) correlates more highly with BED than with other eating disorders.9

A case–control study showed that patients with BED, compared with controls, reported a significantly greater number of adverse life events during the year prior to symptom onset, suggesting that the accumulation of stressful events can trigger the disorder.10 Even after weight loss and CBT, patients with BED experienced higher morning basal cortisol levels than did a control group without BED.

Effects of disordered eating patterns on reproductive health

Disordered adolescent eating patterns affect one’s development, with implications for reproductive function. Behaviors associated with risk-taking and self-harm frequently co-exist with eating disorders and increase risks for unplanned pregnancy and sexually transmitted infections. Obesity is strongly associated with conditions that adversely affect reproductive function.

In anovulatory overweight or obese women, sustained gradual weight loss will regulate menstrual cycles and increase the chance of spontaneous ovulation and conception.11Lifestyle modification has been shown to improve reproductive function.

Effects of binge eating disorder on pregnancy

Pre-pregnancy and pregnancy dietary patterns of women with BED may influence pregnancy outcomes. Many obstetricians do not query patients about weight control or disordered eating during pregnancy, and many patients do not seek treatment. Studies evaluating maternal and fetal outcomes in women with eating disorders are limited.

Women with BED during pregnancy are considered high risk. BED treatment during pregnancy is important for long-term management and reduction of harmful behaviors such as smoking; in fact, treatment during pregnancy is particularly likely to produce long-lasting results.

Pregnant patients with BED need frequent prenatal visits to discuss problems related to both nutrition and BED. Healthcare providers (HCPs) should do the following:

• Empower women to discuss weight and body-image concerns during pregnancy;
• Educate patients that uneven weight gain patterns may occur in pregnancy;
• Inform patients that controlling BED during pregnancy reduces the risk for a large-for-gestational-age newborn;
• Provide or refer for dietary support and meal planning;
• Assess and/or refer for management of psychiatric co-morbidities;
• Provide a routine postpartum visit at 1-2 weeks to monitor for relapse or exacerbation of BED; and
• Provide nutritional and dietary counseling for breastfeeding mothers and for the first 6-12 months postpartum.12

Co-morbid physical disorders

Binge eating disorder is associated with multiple physical co-morbidities, with decreased HRQOL and physical and psychosocial functioning.13 A large majority of individuals with BED receive medical treatment for co-morbidities, particularly obesity-related conditions such as type 2 diabetes mellitus (DM). Weight loss in patients with type 2 DM and BED who control their eating habits is similar to that in persons who have never experienced BED. BED may precede bariatric surgery and/or re-emerge post-surgery.

Screening and diagnosis

Assessment for eating disorders, including BED, should be part of a routine health evaluation. HCPs can use an assessment tool or pose a simple screening question in a matter-of-fact, nonjudgmental, empathetic manner to facilitate open conversation: Do you have thoughts, feelings, or behaviors regarding eating, weight, or body image that occupy most of your time or that make you feel out of control? (See Cases 1, 2, and 3.) The SCOFF Questionnaire can be useful. Practical strategies for screening and diagnosis implemented by the authors include the following:
• Use an eating disorder screening question at routine visits as patients age from childhood through the older adult years;
• Engage patients in a conversation about possible BED;
• Maintain accurate chronological weight records;
• Be familiar with DSM-5 diagnostic criteria;
• Obtain a 24-hour written food intake and feelings journal for
7 consecutive days (including weekends) and review the journals with patients;
• Assess for underlying depression or anxiety; initiate medication if indicated;
• Use physical, nutritional, and psychological findings to incentivize patients to engage in treatment;
• Avoid references to calories, weight, and dieting that may exacerbate feelings of shame or excessive focus on food;
• Advocate an approach for treatment of BED and obesity that does not center on the need for dieting but, instead, emphasizes the importance of specialized psychological, medical, and nutritional care;
• Be familiar with eating disorder specialists in your geographic area and be able to implement the referral process; and
• Confirm that patients follow through with BED treatment.

Binge-eating disorder subtypes may manifest in difficult-to-treat food addictions, which are common in patients with co-existing histories of addictive personality or substance abuse disorder. A marker of substance dependence includes consumption of high-fat/high-sugar foods.14 A food addiction symptom count (using criteria similar to those for substance abuse disorder in the DSM-5) should be obtained for these patients.15 Emotions associated with binge eating may be experienced differently by individuals from specific ethnic, racial, and cultural groups.

Treatment

The American Psychiatric Association has established levels of care guidelines for patients with eating disorders, who can be difficult to treat. Many patients with BED experience shame, embarrassment, self-disgust, depression, and guilt as a result of their eating disorder. They tend to eat secretly or alone and may hide binge foods. Patients may deny that they have an eating disorder and may be reluctant to discuss BED with their HCP. Many patients who use binge eating to deal with difficult life situations are reluctant to eliminate this behavior and do not fully commit to a treatment program. Others welcome interventions that may improve HRQOL.

Nonpharmacologic approaches
Cognitive behavioral therapy, considered a first-line therapy for BED, and interpersonal psychotherapy are effective in patients with BED (See Cases 1, 2, and 3). Other nondrug approaches usually entail a combination of a lifetime nutritional plan, assertiveness training, improved stress management, and moderate exercise to increase lean muscle mass.

Pharmacotherapy
No agent is FDA-approved for the treatment of BED. An application for an indication for lisdexamfetamine dimesylate as a treatment for BED likely will be filed soon with the FDA. Multiple pharmacologic agents have demonstrated benefits at varying dosages in trials conducted between 2005 and 2010.

Antidepressants
Antidepressants address common mood-related co-morbidities. Of note, many patients with BED consume tryptophan-containing carbohydrates that synthesize serotonin. When these patients’ serotonin levels are low, cravings commence. Antidepressants that inhibit reuptake of serotonin can help decrease compulsive/binge eating. In many patients with co-morbid depression (or if CBT is unavailable), selective serotonin reuptake inhibitors (SSRIs) can decrease bingeing (and purging) by 50%, although some patients may not respond to treatment or may relapse with SSRI dis­continua­tion.16 Bupropion has beneficial effects on weight and does not have SSRI side effects. Bupropion dosages of 300-450 mg/day have been shown to be effective.17Psychostimulants
Agents used to treat attention defi­cit hyper­activity disorder (ADHD) affect dopamine/norepinephrine systems associated with both the etiology of BED and eating behavior/reward behavior. An epide­miologic relationship between BED and ADHD has been noted in adolescents18 and adults.19 An association has also been reported between bulimia nervosa (BN) and ADHD; a small study of patients with co-morbid BN and ADHD showed the efficacy of psycho­stim­­ulant medication. An ongoing study is comparing methyl­phen­i­date with CBT in the treat­ment of BED.20Pharmacotherapy during pregnancy
Few studies have evaluated the use of psychotropic agents during pregnancy other than a large cohort evaluation of SSRIs. Additional data may guide decision making regarding the use of agents such as bupropion, methylphenidate, memantine, naltrexone, sodium oxybate, topiramate, and zonisamide in pregnant women.

Conclusion

Binge-eating disorder is a complex, multifactorial condition that requires a comprehensive and integrated course of treatment. Nurse practitioners and other advanced practice HCPs caring for women are positioned to play important roles in patient assessment and management.

References
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Washington, DC: American Psychiatric Association; 2013.

2. Witt AA, Lowe MR. Hedonic hunger and binge eating among women with eating disorders. Int J Eating Disord. 2014;47(3):273-280.

3. Jacobi C, Hayward C, de Zwaan M, et al. Coming to terms with risk factors for eating disorders: application of risk terminology and suggestions for a general taxonomy. Psychol Bull. 2004;130(1):19-65.

4. Jacobi C, Paul T, de Zwaan M, et al. Specificity of self-concept disturbances in eating disorders. Int J Eat Disord. 2004;35(2):204-210.

5. Dunkley DM, Mashib RM, Grilo CM. Childhood maltreatment, depressive symptoms, and body dissatisfaction in patients with binge eating disorder: the mediating role of self-criticism. Int J Eat Disord. 2010;43(3):274-281.

6. Skinner HH, Haines J, Austin SB, Field AE. A prospective study of overeating, binge eating and depressive symptoms among adolescent and young adult women. J Adolesc Health. 2012;50(5):478-483.

7. Vancampfort D, Vanderlinden J, De Hert M, et al. A systematic review on physical therapy interventions for patients with binge eating disorder. Disabil Rehabil. 2013;35
(26):2191-2196.

8. Bulik CM, Sullivan PF, Kendler KS. Medical and psychiatric morbidity in obese women with and without binge eating. Int J Eat Disord. 2002; 32(1):72-78.

9. Wheeler K, Gruner P, Boulton M. Exploring alexithymia, depression and binge eating in self-reported eating disorders in women. Perspect Psych Care. 2005;41(3):114-123.

10. Pike KM, Wilfley D, Hilbert A, et al. Antecedent life events of binge-eating disorder. Psychiatry Res. 2006;142(1):19-29.

11. Pandey S, Pandey S, Maheshware A, Bhattacharya S. The impact of female obesity on the outcome of fertility treatment. J Hum Reprod Sci. 2010;3(2):62-67.

12. Harris AA. Practical advice for caring for women with eating disorders during the perinatal period. J Midwifery Womens Health. 2010;55 (6):579-586.

13. Rieger E, Wilfley DE, Stein RI, et al. Comparison of quality of life in obese individuals with and without binge eating disorders. Int J Eat Disord. 2005;37(3):234-240.

14. Cooper R. Could your patient have an eating disorder? Nurs Womens Health. 2013;17(4):317-324.

15. Gearhardt AN, Corbin WR, Brownell KD. Preliminary validation of the Yale food addiction scale. Appetite. 2009;52(2):430-436.

16. Mehler PS, Anderson AE. Eating Disorders: A Guide to Medical Care and Complications. 2nd ed. Baltimore, MD: John Hopkins University Press; 2010.

17. Stahl SM, Pradko JF, Haight BR, et al. A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiatry. 2004;6(4):159-166.

18. Swanson SA, Crow SJ, Le Grange D, et al. Prevalence and correlates of eating disorders in adolescents: results from the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry. 2011;68(7):714-723.

19. Hudson J, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry. 2007;61(3):348-358.

20. Quilty LC, Kaplan A. Center for Addiction and Mental Health, Toronto, Ontario, Canada. Methylpheni­date versus cognitive behavior therapy in overweight or obese adult females. ClinicalTrials.gov. 2014.

Assessment and management of patients with obesity

Obesity is a disease, not a condition resulting from ill-advised behavioral choices. 1 After all, obesity meets the essential criteria of a disease: It has characteristic signs or symptoms; it manifests as an impairment in the normal functioning of some aspect of the body; and it results in harm or morbidity. As such, healthcare providers (HCPs) need to identify obesity in their patients, assess each patient’s risk for obesity-related complications, begin the weight-loss discussion in a thoughtful and constructive manner, and institute an individualized management plan.

Definitions and prevalence

Obesity can be defined as a body mass index (BMI) ?30 kg/m2 or it can be suggested by a waist circumference (WC) >35 inches (in women).2 But obesity is more than just a calculation or a measurement; it is a primary disease entity that can lead to cardiometabolic, biomechanical, and other complications (Figure 1).3,4CNER_Figure 1

 

 

 

 

 

 

 

 

 

 

 

 

Here is a number that matters: Almost 80 million U.S. adults—almost 35% of the adult population in this country—meet criteria for obesity,5 with certain geographic areas and certain ethnic groups overrepresented. Prevalence of obesity is higher in southern states and some Midwestern states than in other parts of the country,6 as illustrated by this CDC map. Non-Hispanic blacks have the highest age-adjusted rate of obesity (47.8%), followed by Hispanics (42.5%), non-Hispanic whites (32.6%), and non-Hispanic Asians (10.8%).5 Although overall obesity prevalence is similar in women and men at any given age, women have a higher prevalence of class II obesity (BMI, 35.0-39.9) and class III obesity (BMI ?40).7

Risk assessment

Given the high prevalence of obesity, HCPs will likely encounter many patients in their practices who are candidates for weight management. In each case in which obesity is identified, the first step needed is to assess the patient’s risk for obesity-related complications. This assessment includes calculating BMI, measuring WC, and screening for the presence of cardiovascular disease (CVD) risk factors and co-morbidities.8 Compared with body weight alone, BMI is a better, albeit indirect, measure of adiposity, which is associated with a host of cardiometabolic abnormalities. WC, an indicator of abdominal adiposity, should be measured in patients with a BMI ?35 (the WC cutoff of >35 inches in women adds little predictive value in those with a BMI >35), including those who are overweight (BMI, 25-29.9). Women whose WC exceeds 35 inches are at increased risk for developing hypertension (HTN), type 2 diabetes mellitus (T2DM), and CVD.

Therefore, HCPs need to check patients’ blood pressure (BP) to assess for HTN and order a fasting blood glucose (FBG) test, and even a 2-hour oral glucose tolerance test and HbA1c in high-risk individuals, to assess for T2DM and pre-diabetes.9 The metabolic syndrome, which increases risk for T2DM, CVD, and stroke, is identified in women by the presence of at least three of these five risk factors: WC >35 inches, triglycerides ?150 mg/dL, high-density lipo­protein cholesterol (HDL-C) <50 mg/dL, BP ?130/85 mm Hg, and FBG ?100 mg/dL.10

Some obesity-associated diseases and risk factors place patients in a very-high-risk category for subsequent mortality.8 Patients with obesity and co-morbid coronary heart disease (CHD), other atherosclerotic diseases, T2DM, metabolic syndrome, pre-diabetes, or sleep apnea require aggressive modification of risk factors in addition to clinical management of the co-morbid disease. Furthermore, obesity has an aggravating effect on CVD risk factors such as cigarette smoking, HTN, high concentration of low-density lipoprotein cholesterol, low concentration of HDL-C, impaired FBG, family history of premature CHD, and age ?55 years (in women). HCPs need to identify these risk factors to determine the intensity of the clinical intervention that a patient requires.
Obesity takes a toll not just in terms of its effect on CVD risk, but also on cancer risk. The Cancer Research UK study showed that women with obesity had a 25% risk of developing a weight-related cancer—including cancer
of the bowel, gallbladder, uterus, kidney, pancreas, or esophagus, as well as post-menopausal breast cancer—in their lifetime.11 Cancer risk in these women was 40% higher than that in their slimmer counterparts.

Initiating the conversation

Either a patient or an HCP can initiate the conversation regarding the need to lose weight. The situation is generally easier to handle when a patient expresses a desire to lose weight. She has already acknowledged existence of the disease—that is, the obesity—and is seeking treatment for it on her own. However, in many cases, the HCP must broach the topic, usually after a patient has come in for a routine visit and the findings from her history, physical examination, and laboratory tests indicate that steps must be taken to lower her risk for experiencing obesity-related complications—or to treat the complications that already exist.

To avoid discomfiting a patient in this situation, a panel of nurse practitioners convened by the American Nurse Practitioner Foundation (ANPF) recommends that the HCP show her objective data reflecting her disease and her risk for future complications—with an emphasis that obesity is a health problem—and then assess her motivation and readiness for change.7 In this context, the HCP and the patient need to synchronize their expectations and goals for weight loss therapy. HCPs now have reliable tools to help patients lose 5%-10% of their body weight. This weight loss may not produce the desired cosmetic outcome but will no doubt result in clinical benefits. The emphasis is on improving the health of the patient.

To inspire a patient with obesity to want to lose weight and to commit to follow a weight-loss treatment plan, the HCP can help her identify at least one compelling reason to lose weight.7 Common patient-centered reasons include (1) decreasing the risk of having a complicated pregnancy; (2) being able to play with children or grandchildren; (3) walking without becoming short of breath; (4) preventing other chronic diseases such as T2DM; and (5) improving existing weight-related complications such as sleep apnea or T2DM. Of note, some patients may not be aware of the health risks posed by obesity and will be motivated to lose weight once educated about the risks.

Approach to management

Once a patient with obesity is motivated and ready to lose weight, the HCP needs to work with her to devise a management plan. Both of them should agree on the goals of weight-loss therapy and on the purpose of long-term therapy. A realistic initial goal for many patients is a loss of 5% of body weight in 3 months. Three major management options—lifestyle modification, pharmacotherapy, and bariatric surgery—can bring about weight loss and reduce obesity-related morbidity and mortality.1 This article focuses on the first two options.

Lifestyle modification

A comprehensive weight-loss program starts with lifestyle modification comprised of dietary changes, increased activity, and behavioral control.12

Dietary changes

With regard to energy intake, the ANPF recommends a reduction of 500-1,000 kcal/day, which can be accomplished by limiting portion size, reducing fat and sugar intake, and using commercial weight-loss meal replacements.7 The patient can follow one of many diets shown to be safe and effective; examples are a low-carbohydrate diet,13 a low-fat diet,14 a Mediterranean diet,15 a low-glycemic-load diet,16 and a portion-controlled diet.17

Practical dietary tips include avoiding skipping meals and consuming small meals and between-meal snacks every 3-4 hours. With regard to food intake, moderation is the watchword. With regard to fluid intake, however, drinking eight 8-oz glasses of water a day is crucial unless contraindicated (e.g., in patients with renal failure).

Choice of a particular diet is less important than making a commitment and adhering to the diet,18 although following a regimen tailored for a co-morbidity makes sense. Because compliance is the key to success, the diet plan should accommodate the patient’s personal and cultural preferences. Regardless of the diet chosen, patients should monitor their caloric intake via a food diary and weigh themselves at least once a week.19

Increased activity

Choice of a particular activity (e.g., walking, swimming) depends on a patient’s preference and access to, say, a pool, as well as her current weight and health status. An assessment of mobility, cardiovascular (CV) status, and perhaps pulmonary function is needed before a patient embarks on a new exercise program.20 The goal is to increase energy expenditure.20 Exercising for ?150 minutes/week can lead to modest weight loss and help prevent weight regain; doubling this amount will promote more robust weight loss.21 As with food intake, patients should record their daily physical activity.

Exercise not only facilitates weight loss but also improves CV health by reducing BP, lipid levels, and visceral fat. These reductions are linked to improved glucose tolerance and insulin sensitivity in persons without diabetes and improved glycemic control in patients with T2DM.12 Enhanced physical fitness may even lessen obesity-related mortality. Of note, patients with obesity must modify their diet and increase physical activity in order to lose weight and reduce their risk for obesity-related complications. Another note: In addition to traditional exercise, patients can aim to increase energy expenditure throughout the day by reducing sedentary behaviors. For example, car owners can park twice as far from store entrances as they used to; city dwellers can walk instead of taking a bus, subway, or taxi; and office workers can use a standing desk instead of sitting at their desk.

Behavioral therapy

As applied to weight loss, behavioral therapy entails techniques for helping patients replace habits that contribute to excess weight and poor health with those that promote weight loss and good health.12 Key components of behavioral therapy include frequent encounters with HCPs, education, stimulus control, cognitive restructuring, goal-setting, self-monitoring, and social support.20 Group weight-loss programs in community settings, commercial weight-loss programs, and programs delivered by telephone, the Internet, or text message can all be effective, depending on patient preference.12

Pharmacotherapy

If a patient has not lost about 5% of her body weight after 3 months, or if she has lost weight but regained some, most, or all of it over time, she and her HCP should consider use of weight-loss medication as an adjunct to lifestyle modification. In some patients with severe complications who require clinically meaningful weight loss quickly, lifestyle modification and pharmacotherapy can be initiated concomitantly.

Rationale

In all human beings, calorie restriction triggers various biological adaptations designed to prevent starvation.22 These adaptations may even be potent enough to reverse the initial weight-loss success achieved with lifestyle modification. In persons with obesity, additional biological adaptations function to preserve, or even increase, their highest sustained lifetime body weight. As such, more biologically-based interventions are likely to be needed to counter the compensatory adaptations that maintain a person’s highest lifetime body weight.22 Other reasons for pharmacologic intervention in facilitating weight loss include the following:

  • Appetite-suppressing medication enhances a patient’s ability to adhere to a reduced-calorie diet.
  • Addition of a weight-loss medication consistently achieves greater weight loss, and for a longer duration of time, than that achieved by the lifestyle intervention alone.
  • Medication can help achieve the degree of weight loss needed to treat obesity-related complications.
  • The American Association of Clinical Endocrinologists (AACE), the American Society of Bariatric Physicians (ASBP), the American Heart Association (AHA), the American College of Cardiology (ACC), and The Obesity Society (TOS) all recommend use of medication for patients with obesity and sufficient health risk.20,23,24

Principles for use

The FDA indication for use of weight-loss medications is a BMI ?30 or a BMI of 27-29.9 with at least one obesity-related complication. The medication should be stopped if weight loss is <5% after 12 weeks on a maximal dosage. If one agent is ineffective or poorly tolerated, a different one can be tried. All of these agents are contraindicated for use during pregnancy. Pharmacotherapy is individually tailored to each patient’s needs. More data are needed regarding the safety of combination therapy and the use of medications beyond 2 years.

Options

Table 1 lists FDA-approved options for treating obesity.25-31Table 2. Weight-loss medications: Clinical trial information, accessible through this link, shows the results of clinical trials demonstrating the efficacy of these agents.32-39Figure 2 illustrates the comparative efficacy of these weight-loss medications.32-36,38-45
CNe_Table 1

 

CNE Figure 2

Guidelines for practice

The spectrum of obesity treatment guidelines ranges from those that are BMI-centric, wherein treatment indication is based on BMI and the treatment goal is to lose a given amount of weight (e.g., 5%-10%), to those that are complications-centric, wherein treatment indication is based on risk for, presence of, and severity of obesity-related complications and the treatment goal is to treat or prevent the complications.46Obesity treatment guide­lines from the National Heart, Lung, and Blood Institute (NHLBI), at one end of the spectrum, are based primarily on BMI and WC, although risk factors and co-morbidities are taken into account.8 The AACE, at the other end of the spectrum, recommends (1) evaluating patients with obesity for cardiometabolic and biomechanical complications; (2) selecting (a) therapeutic targets for improvements in complications, (b) treatment modality, and (c) treatment intensity; and (3) intensifying lifestyle and/or pharmacologic and/or surgical treatment modalities for greater weight loss if therapeutic targets for improvements in complications are not met.23Table 3 lists percentages of weight loss needed to achieve therapeutic benefits with regard to various obesity-related complications.4CNE_Table3

 

The AHA/ACC/TOS obesity guideline, which is closer to that of the NHLBI, recommends (1) identifying patients who need to lose weight, based on BMI and WC; (2) informing patients with CVD risk factors that lifestyle changes that produce even modest sustained weight loss of 3%-5% can result in clinically meaningful health benefits, and that greater weight loss produces greater benefits; (3) devising dietary strategies for weight loss; (4) devising a comprehensive lifestyle program that helps patients adhere to a lower-calorie diet and increase physical activity through use of behavioral strategies; and (5) selecting patients for whom bariatric surgery is advised—that is, those with a BMI ?40 or a BMI ?35 with obesity-related conditions.24 The approach of the ASBP to obesity management, which is closer to that of the AACE, focuses on treating diseases related to increased body fat and its adverse metabolic and biomechanical consequences, which may improve patient health, quality of life, body weight, and body composition.20

Conclusion

Obesity is a disease that requires permanent lifestyle changes. Lifestyle modification, enabled by dietary changes, increased physical activity, and behavioral therapy, is implemented first. If a patient does not reach her goals in terms of reducing her weight and her risk for obesity-related complications, medication is added. Most medications suppress appetite, enhance a patient’s ability to follow a reduced-calorie diet, and enable significantly greater weight loss than that achieved by lifestyle changes alone. In addition, medication use can help sustain weight loss and prevent weight regain over time.

For patients with obesity and obesity-related co-morbidities, weight loss is used therapeutically to treat the obesity-related complications. The role of the HCP is to diagnose the disease of obesity, assess the patient’s risk for obesity-related complications, discuss weight-loss strategies and goals with the patient, support the patient in implementing these strategies and reaching these goals, and provide regular follow-up and encouragement over the ensuing months, years, and decades.

For readers of the online issue who wish to participate in this CE program, click here.

Visit http://www.NPWomensHealthcare.com/?p=4144 for a complete list of references.

 

Individualizing contraception

Contraceptive counseling: Why is it so important?

The disconnect between two seemingly contradictory facts— effective contraception is widely available, but almost half of pregnancies in the United States are unintended—highlights the need for better communication between healthcare practitioners (HCPs) and their patients about contraception and the development of strategies to increase patient adherence to and satisfaction with contraceptive regimens. Women also need more information about how to use and obtain emergency contraceptives (ECs).

Among the 6.4 million pregnancies that occur in the United States each year, 49% are unintended. 1 Of these unintended pregnancies, 29% happen earlier than desired and 20% happen after women have reached their desired family size. In addition, of these unintended pregnancies, 52% occur in the absence of the use of contraception, 43% occur with inconsistent or incorrect use, and 5% occur with consistent use and method failure. When asked about reasons for their nonuse of contraception, women report problems accessing or using methods (40%), infrequent sex (19%), lack of caring about whether pregnancy occurs (18%), underestimation of the risk of pregnancy (7%), and other reasons (16%).1

Contraceptives vary in terms of efficacy. Although all contraceptive are highly effective with perfect use, the most effective agents—the hormonal intrauterine contraceptive (IUC), the copper T-380A intrauterine device (IUD), and the subdermal implant— have high levels of efficacy with typical use because there is no user component that may result in incorrect or inconsistent use. Based on typical-use data, the oral contraceptive (OC), the vaginal ring, the patch, and the injection are less effective than IUCs and the implant—primarily because they require user actions and decision making. The least effective options are those that are coitus dependent: condoms, withdrawal, other barrier  methods, and spermicides.2Of note, the highest levels of satisfaction with contraceptives are reported by users of IUCs and the ring.3

Forty-six percent of women discontinue a birth control method because of dissatisfaction. 4 To reduce this discontinuation rate, HCPs need to provide effective counseling. Such counseling requires asking patients about their goals and attitudes regarding contraception and then listening carefully to their answers. That way, HCPs can be confident that they are prescribing the form of contraception that will best meet patients’needs and with which they will be most satisfied. Reports suggest that inconsistent use of combined OCs (COCs)—that is, those containing an estrogen and a progestogen—is more common among women who are not completely satisfied with their method.4

Healthcare practitioners must provide each patient with a knowledge base so that she can make informed decisions about birth control and birth control options. In the process, HCPs may need to correct deeply entrenched misinformation. HCPs also must provide anticipatory guidance about the use and the side effects of contraceptives and ECs. The bottom line: Patients need to leave the office knowing what to expect from the contraceptive they have selected and they need to know how to obtain and use an EC in the event of contraceptive mishap (e.g., torn condom, dislodged diaphragm) or nonadherence.

Strategies for selecting a contraceptive

Strategy 1: Set the stage for an effective visit. Although HCPs are pressed for time, they can obtain key information to help them partner with a patient and help her select the most appropriate contraceptive option for her before she even enters the examination room. When a patient calls to schedule an appointment with a goal of contraceptive counseling, she can be referred to the Association of Reproductive Health Professionals method match website.

This website will enable the patient to become familiar with the options and evaluate them prior to her visit. On standard forms that a patient completes in the waiting room, HCPs can include questions about pregnancy plans. Do you desire a pregnancy within 1 year? Within 1-3 years? Within 3-5 years? Not for 5-10 years or more? Not at all? Her answer will help you narrow down the list of options. Next, ask the patient about her contraceptive history: What forms of contraception have you used? What did you like/dislike about each method?

Discuss contraception prior to the physical examination, while the patient is still clothed; she is unlikely to give you her full attention if she is trying to keep the paper drape closed. Have samples of the contraceptive products in the exam room so that the patient can see and handle them.

Strategy 2: Analyze perfect use versus typical use. The level of participation and decision making required of patients in the use of a contraceptive method accounts for the gap between perfect use and typical use. The more user participation that is needed (e.g., remembering to take a pill every day), the greater the gap between perfect use and typical use. Although all contraceptives used correctly and consistently offer excellent efficacy, first-year rates of unintended pregnancy associated with typical use range from 8% with OCs to less than 1% for long-acting reversible contraceptives (LARCs; i.e., IUCs and implants) that require no patient participation or decision making.5

Therefore, each patient should be asked about how she will manage the use of contraceptives that require daily, monthly, or quarterly actions on her part. Ask her, “If you choose condoms or OCs, will you be able to manage them? These forms of contraception take more work on your part. Conversely, a long-acting method frees you from having to think about it; put it in and forget it.” The rate of non-LARC contraceptive failure is particularly high for adolescents. Among users of OCs, the patch, or the ring, the yearly failure rate in the first year of use is 8.2% among women aged 30 years or older and 13.4% among adolescents.6,7

Strategy 3: Teach patients that LARCs are more effective than other methods in preventing unplanned pregnancy, especially over time. Long-term use of agents that require decision making on a patient’s part, as compared with long-term use of LARCs, is associated with increased risk of incorrect or inconsistent use and pregnancy. This finding was confirmed in a recent study of 7,486 women using LARCs (i.e., IUCs or implants) or another commonly prescribed contraceptive (OC, patch, ring, or depot medroxyprogesterone acetate [DMPA] injection).7The contraceptive failure rate among participants using non-LARCs— that is, OCs, the patch, or the ring—was 4.55 per 100 participant- years, as compared with 0.27 among participants using LARCs (adjusted hazard ratio [HR], 21.8; 95% confidence interval (CI), 13.7-34.9). Rates of unintended pregnancy were similarly low among participants receiving the DMPA injection and those using an IUD or an implant. In this investigation, for users of OCs, the patch, or the ring, the contraceptive failure rate increased over time, from about 5% in year 1 to nearly 8% in year 2 and more than 9% in year 3. LARCs, including DMPA, had failure rates of less than 1% for each of the 3 years. Therefore, the need for correct and consistent use of contraception should be reviewed at each patient visit, year after year.

Strategy 4: Assess the options that best meet an individual patient’s needs. Ask each patient how the methods that interest her will fit into her life—now and, in light of ongoing concerns regarding adherence, in the future. How will each method fit into her schedule? For example, how will she remember to take the pill or change the patch? Which bleeding patterns will be acceptable? If, in the first few months, a patient does not know when bleeding is likely to occur, will this be a problem for her? Is privacy of the method a concern? Are there any financial barriers? If so, are there assistance programs or installment payment plans available? Review the patient’s record for any conditions (e.g., dysmenorrhea, heavy menstrual bleeding, menstrual migraine, acne) that could be simultaneously managed by specific methods. Finally, determine whether the patient has any contraindications to any birth control methods. For example, use of combined hormonal contraceptives is contraindicated in patients with migraine with aura and in users of certain types of anticonvulsants.

Strategy 5: Dispel myths, especially those related to IUCs. To dispel common misconceptions about IUCs, discuss their mechanism of action with patients These devices prevent fertilization; they do not cause abortions.2,8 Another myth to dispel is any association between IUC use and an increased risk of ectopic pregnancy. The contraceptive effectiveness of these devices is 99.9%; the risk of pregnancy is very small. In the event that pregnancy should occur, the possibility of an ectopic pregnancy is of concern, but the likelihood  such an occurrence is minute.2,8

Testing for sexually transmitted infections (STIs) in women scheduled to undergo IUC insertion is generally not done unless they are at risk for chlamydia and gonorrhea (e.g., women aged 25 years or younger). Risk of pelvic inflammatory disease is higher at IUC insertion only if a woman tests positive for chlamydia or gonorrhea.2,8

Strategy 6: Help your patient be successful in adhering to her contraception regimen. Once a woman has selected a contraceptive, help her be successful in its use. This checklist can help ensure that she has the tools she needs for success. Your patient…

Leaves the office knowing, in simple terms, how the option she has selected works;

Understands how to use the method correctly;

Is aware of the side effects, which you have explained using simple terms;

Knows the warning signs that signal potential complications and what her course of action should be;

Understands the indications for EC use and knows where and how to obtain an EC;

Realizes that, if she doesn’t like her contraceptive choice, she can return to your office for assistance in choosing a different method that is better suited to her needs;

Has resources to help her remember key points about the contraceptive she has chosen, including handouts and information about websites that provide accurate information;

Knows that she will still need to protect herself against STIs.

Emergency contraception

Many HCPs are uncomfortable with the topic of emergency contraception and do not discuss it unless a patient asks about it. In patients’ best interest, though, HCPs need to use every visit as an opportunity to discuss contraception and the potential need for an EC. ECs are defined as contraceptives intended to prevent pregnancy within the first few days of unprotected sex. The most commonly used ECs contain oral levonorgestrel (LNG). Ulipristal acetate, a selective progesterone receptor modulator, is another oral EC. Another effective method of EC available is the copper IUD, which is used off label for this indication.

Levonorgestrel agents are available in two over-the-counter dosing regimens.9-14The onetablet regimen contains LNG 1.5 mg. On label, this product is taken within 72 hours after unprotected intercourse, when it is most effective. Off label, it can be used up to 120 hours after intercourse. The second regimen is a two-tablet product that also contains a total of 1.5 mg of LNG (0.75 mg per pill). The package labeling states that one pill is taken immediately after unprotected intercourse and the second pill, 12 hours later. Off-label directions are to take both pills at  once, preferably within 72 hours of unprotected intercourse. For both LNG regimens, greatest efficacy  is achieved when the medication is taken within 72 hours of unprotected intercourse, but efficacy has been demonstrated up to 120 hours after unprotected intercourse. After EC use, a highly effective contraceptive should be started; a backup method (e.g., condoms) is needed for 7 days.

Ulipristal acetate 30 mg is available by prescription.13-16 This product can be used during the first 120 hours after unprotected intercourse. Unlike other agents, ulipristal acetate maintains efficacy during the full 120 hours after intercourse. This EC, which is highly effective in obese women as well as their normal-weight counterparts, may be ordered from an online prescription service. After use, a highly effective contraceptive should be started; a backup method is needed for 14 days.

The copper IUD can provide emergency contraception within 5 days of unprotected intercourse. Although use of the copper IUD is off label for this indication, one advantage is that this product can then be retained as a long-acting contraceptive. Efficacy of this EC method was shown in a prospective study of 542 women who presented for emergency contraception. 17The 1-year cumulative pregnancy rate in women choosing the copper IUD was 6.5%, as compared with 12.2% in those choosing oral LNG (HR, 0.53; 95% CI, 0.29-0.97; P = .041]. Thus, 1 year after presenting for emergency contraception, women choosing the copper IUD were half as likely as those choosing oral LNG to have a pregnancy.

Strategy 7: Ensure access to ECs. Results of a 2013 patient survey by NPWH have shown that more than 75% of HCPs do not discuss emergency contraception with their patients. However, patients who find themselves in need of an EC should learn about it through communication with their HCP. Furthermore, a 2011 survey distributed to the email database of NPWH (N = 10,800) and completed by 699 clinicians showed important gaps in best practices in patient care among the respondents:

• 55.3% reported that they review EC options with each reproductive aged patient.

• Although 88.2% of respondents  said that they tell patients about LNG, only 26.5% reported discussing ulipristal acetate; 21.9%, the copper IUD; and 16.1%, the Yuzpe method.

• Only 44.3% of respondents said that they provide information and/or a prescription for an EC to all patients who do not desire pregnancy.

In view of the fact that 49% of pregnancies in the U.S. are unintended, HCPs are advised to review EC use and availability at each office visit by (1) explaining what EC does, how it works, and when to use it; (2) providing an anticipatory prescription; and (3) reviewing and dispelling myths about ECs. Concerns about ECs’ mechanisms of action remain associated with major barriers to use.14 Many women believe that ECs are abortifacients with long-term effects on health and fertility. 18A patient’s poor understanding of reproductive physiology may result in confusion as to when ECs are most effective. 19,20

Case studies

Case 1: Tanya is 24 years old, is 5’5″, weighs 121 lb (body mass index [BMI], 20.1 kg/m2), and has no prior pregnancies or health problems. Tanya schedules a visit to request a different OC because of bothersome light bleeding for the past 3 months.  She currently uses a COC containing ethinyl estradiol 20 mcg and norethindrone. Further discussion reveals that Tanya skips taking her birth control pill no more than once a week. She has had three male partners in the past 3 months and reports condom use about half the time. She reports smoking about 10 cigarettes a day,

Assessment. Begin by doing a workup concerning the abnormal bleeding, which may or may not be related to the COC regimen. Rule out pregnancy and STIs and perform speculum and bimanual examinations. Because Tanya has no mucopurulent cervicitis, discharge, or tenderness, and her test results are all negative, you conclude that the irregular bleeding is a side effect of the COC use. As you recall, the longer a patient uses a method, the more likely she is to use it incorrectly.

Counseling. Develop strategies to encourage correct and consistent COC use. In this case, consider changing formulations to reduce side effects. Review all the options with Tanya. Take this opportunity to discuss nondaily methods. Although Tanya is not a heavy smoker, remind her that her nicotine intake could be sufficient to induce breakthrough bleeding. Discuss safer sex and the importance of protecting herself from STIs. Review the indications for EC use. Make sure she knows how and where to obtain an EC. Provide a prescription for an EC product.

Patient decision. Tanya is interested in using a nondaily contraceptive and wants to try the ring. Discuss the use, side effects, and warning signs, and reinforce the fact that the ring will not protect against STIs. If the device is expelled or if Tanya is not punctual about replacing the ring, she will need to use an EC following unprotected intercourse. Schedule a follow-up visit to discuss Tanya’s satisfaction with the ring. At a follow-up visit, Tanya indicates that she likes the ring and has had no episodes of unscheduled bleeding.

Case 2: Annette is 17 years old, is 5’7″, weighs 220 lb (BMI, 34.5 kg/m2), and has had no prior pregnancies. Annette has scheduled her appointment for contraceptive counseling and looks to you for advice.

Assessment. Annette’s history includes obesity, migraine with aura, dysmenorrhea, and menorrhagia. Her partner uses condoms about half the time. She worries about weight gain with hormonal contraceptives. She is uncertain about her ability to remember to take a daily pill. Because of her migraine with aura, methods that contain estrogen are contraindicated. A patient with migraine without aura could use estrogen products as long as her blood pressure is monitored and her headache severity and frequency are not adversely affected. Progestin-only pills (POPs) would be a good option if Annette had indicated a willingness to use them consistently. DMPA can be associated with weight gain, which is already a concern for her.

The LNG intrauterine system (IUS) represents a good option because it may help alleviate Annette’s cramping and bleeding, which would be likely to increase her satisfaction with this method. An implant might be a good choice, but she likes the longer duration associated with the LNG IUS. The 10-year duration of the copper IUD appeals to her, but she would like the reduction in menstrual problems that may result from use of the LNG IUS.

Patient decision. Annette selects the LNG IUS. Review the mechanism of action, side effects, and warnings, with an emphasis on the transitional bleeding interval. Although bleeding patterns will likely normalize within 3 months, tell her that it may take 6 months. This strategy accounts for the variability in duration and reduces the potential for frustration. Review safer sex and condom use at the initial discussion and before and after placement of the device.

Case 3: Regina is 44 years old, is 5’5″, weighs 200 lb (BMI, 33.3 kg/m2), and has no history of pregnancy. Regina has scheduled a visit for her well-woman examination. She has not been sexually active since her divorce, but she has started a relationship that she believes may become serious. Therefore, you initiate a discussion about contraception.

Assessment. Regina’s history is unremarkable except for a cholecystectomy at age 30. Her menstrual history remains normal, with menses marked by predictable intervals, duration, and cramps, all of which indicate ovulation. She takes naproxen sodium for moderate to severe cramps. Regina has a demanding job in advertising and travels often, noting fatigue associated with erratic schedules and frequent time zone changes. Her variable schedule makes it difficult to sustain an exercise regimen. She indicates that she would like to exercise more regularly to lose weight. Regina and her husband got divorced 5 years ago; early in the marriage, they had decided not to have children. He underwent a vasectomy. A nonsmoker, she drinks wine 1-2 times a week in social settings.

Counseling. Regina does not use contraception. However, data show that unplanned pregnancy is most likely among younger and older women. Convey to Regina that in women of her age, pregnancy is associated with an increased risk for maternal mortality, spontaneous abortion, and fetal abnormalities. Discuss ECs, safer sex, and STI risk.

Patient decision. Based on her profile, Regina is eligible for any contraceptive, although the patch may be less effective because she weighs more than 198 lb. Other less-than-optimal choices are COCs or POPs because she has indicated that she has an irregular daily routine and schedule. She is more interested in an IUD; either the LNH IUS or the copper IUD is appropriate for her. She considers each option: 5-year versus 10-year efficacy and hormonal versus nonhormonal characteristics.

Regina wants to do some research on her own. Refer her to a reliable website such as www. arhp.org/methodmatch. She plans to start Weight Watchers and a swimming routine that she can implement in many of the hotels at which she stays. You and Regina decide that she will call you as soon as she makes her decision about which IUC to use, and that, in the meantime, she will keep condoms available for use if needed. At her next visit, Regina informs you that she has decided to use the copper IUD because she prefers a nonhoromal method.

A final word about contraceptives and weight gain

Two of the tree cases discussed in the article involve women who are obese. Sixty-four percent of women in this country are overweight and 36% are obese. 21 Therefore, body weight may be an important consideration when choosing a contraceptive; some options may be associated with a tendency for a weight gain and some may not be as effective in obese women.

In terms of the former concern, four randomized, placebo-controlled trials showed no evidence supporting a casual association between use of COCs or a combination patch and weight gain. 22 Results of a similar review were inconclusive with regard to progestin-only contraceptives. 23 However, a prospective study of 450 adolescents showed that among those using DMPA, those who were already obese gained significantly more weight than did their non-obese counterparts. 24 Also, the obese DMPA users gained significantly more weight than did obese COC users or obese nonusers of hormonal contraception. With regard to contraceptive efficacy, the patch may be less effective in women weighing 198 lb or more. 25 With regard to EC efficacy in obese women, ulipristal acetate may be a better choice than LNG-containing ECs.  26

Conclusion

Even though information about contraceptives is readily available in print and online, and even though contraceptives themselves are easily available and, in many cases, fully covered by health insurance payments to pharmacies, many adolescents and women are not using these products correctly, consistently, and persistently. HCPs, including nurse practitioners, can fill in the knowledge gap by making sure to discuss contraceptive needs with all their patients, and to find the product or products that will work best for them.

References

1.  Frost JJ, Darroch JE, Reme L. Improving contraceptive use in the United States. In Brief. Guttmacher Institute. 2008. www.guttmacher.org/pubs/2008/05/09/ImprovingContraceptiveUse.pdf

2. Hatcher RA, Trussell J, Nelson AL, el al, eds. Contraceptive Technology: Twentieth Revised Edition. New York, NY: Ardent Media, Inc.;2011.

3. Revisiting Your Women’s Health Care Visit. Harris Interactive for the Association of Reproductive Health Professionals. Conducted June 30–July 14, 2004.

4. Moreau C, Cleland K, Trussell J. Contraceptive discontinuation attributed to method dissatisfaction in the United States. Contraception. 2007;
76(4):267-272.

5. Trussell J, Guthrie KA. Choosing a contraceptive: efficacy, safety, and personal considerations. In: Hatcher RA, Trussell J, Nelson AL, et al, eds. Contraceptive Technology: Twentieth Revised Edition. New York, NY: Ardent Media; 2011:45-74.

6. Kost K, Singh S, Vaughan B, et al. Estimates of contraceptive failure from the 2002 National Survey of Family Growth. Contraception.2008;77(1):10-21.

7. Winner B, Peipert JF, Zhao Q, et al. Effectiveness of long-acting reversible contraception. N Engl J Med. 2012;366(21):1998-2007.

8. Grimes DA. Intrauterine device and upper-genital-tract infection. Lancet. 2000;356(9234):1013-1019.

9. Arowojolu AO, Okewole IA, Adekunle AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception. 2002;66(4):269-273.

10. Piaggio G, von Hertzen H, Grimes DA, Van Look PF. Timing of emergency contraception with levonorgestrel or the Yuzpe regimen. Task Force on Postovulatory Methods of Fertility Regulation. Lancet. 1999;353(9154):721.

11. von Hertzen H, Piaggio G, Ding J, et al; WHO Research Group on Postovulatory Methods of Fertility Regulation. Low dose mifepristone and two  regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet. 2002;360(9348):1803-1810.

12. Ngai SW, Fan S, Li S, et al. A randomized trial to compare 24 h versus 12 h double dose regimen of levonorgestrel for emergency contraception. Hum Reprod. 2005;20(1):307-311.

13. The Emergency Contraception Website. www.not-2-late.com

14. Reproductive Health Technologies Project website. www.rhtp.org

15. Glasier A, Cameron ST, Blithe D, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception. 2011;84(4):363-367.

16. Moreau C, Trussell J. Results from pooled Phase III studies of ulipristal acetate for emergency contraception. Contraception. 2012;86(6):673-680.

17. Turok DK, Jacobson JC, Dermish AI, et al. Emergency contraception with a copper IUD or oral levonorgestrel: an observational study of 1-year pregnancy rates. Contraception. 2013 Nov 22. Epub ahead of print.

18. Corbett PO, Mitchell CP, Taylor JS, Kemppainen J. Emergency contraception: knowledge and perceptions in a university population. J Am Acad Nurse Pract. 2006;18(4):161-168.

19. Gemzell-Danielsson K, Berger C, P G L L. Emergency contraception —mechanisms of action. Contraception. 2013;87(3):300-308.

20. Shoveller J, Chabot C, Soon JA, et al. Identifying barriers to emergency contraception use among young women from various sociocultural groups in British Columbia, Canada. Perspect Sex Reprod Health.
2007;39(1):13-20.

21. National Institute of Diabetes and Digestive and Kidney Diseases. Weight-control Information Network. Overweight and Obesity among Adults Age 20 and Older, United States, 2009–2010. http://win.niddk.nih.gov/statistics/#b

22. Gallo MF, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 2011;(9):CD003987.

23. Lopez LM, Edelman A, Chen-Mok M, et al. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2011;(4):CD008815.

24. Bonny AE, Ziegler J, Harvey R, et al. Weight gain in obese and non-obese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method. Arch Pediatr Adolesc Med. 2006;160(1):40-45.

25. Ortho Evra website. JanssenPharmaceuticals, Inc. 2014. http://www.orthoevra.com/

26. Batur P. Emergency contraception: separating fact from fiction. Cleve Clin J Med. 2012;79(11):771-776.

 

 

Evaluation of women with infertility

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Key words: infertility, infertility evaluation, ovulatory dysfunction, ovarian reserve, tubal patency

Advanced practice nurses (APNs) may be the first point of contact in a woman’s lengthy fertility journey. Although caring for a patient with infertility is within the scope of practice of APNs, this process can be intimidating and complex. APNs need to set realistic expectations, educate patients, and provide initial management. The author discusses the initial evaluation of a woman with infertility prior to a referral to a reproductive endocrinology and infertility specialist if necessary.

As many as 15% of couples trying to conceive a child are diagnosed with infertility, defined as the inability to conceive within 1 year despite unprotected intercourse.1 Because advancing maternal age is a driving force in the decline of fertility, the time span in the definition may reasonably be altered to 6 months for women older than 35 years. Overall fertility rates, which peak between the ages of 20 and 24 years, are 4%-8% lower in women aged 24-29, 15%-19% lower in those aged 30-34, 26%-46% lower in those aged 35-39, and as much as 95% lower in those aged 40-45.1 

Infertility is a complex diagnosis that can greatly affect physical, mental, and financial aspects of a couple’s life together.2 In general, infertility is considered a couple’s diagnosis because 35%-40% of cases are due to male factors, 30%-40% to female factors, and up to 30% to a combination of male and female factors or unexplained factors.1 Common causes of infertility in women are ovulatory dysfunction and tubal/peritoneal pathology, and a common cause of infertility in men is a sperm abnormality.3 

Referral to a specialist in reproductive endocrinology and infertility (REI) is considered early in the assessment of infertility in a woman with endometriosis, tubal disease, a history of three or more spontaneous abortions, or previous ovulation induction, or in a case of male factor infertility. When known risk factors exist, or when a woman is older than 35 years, APNs should not wait to initiate assessment and referral until a couple has tried to conceive for a full year. However, women who have not previously tried ovulation induction medications, are anovulatory, have polycystic ovary syndrome (PCOS), or have unexplained infertility may be treated by an APN for 3-6 months prior to referral.4 Male factor infertility may be addressed with an intrauterine insemination if an andrology laboratory is available. Knowing the appropriate components and timing of an infertility assessment is essential.

History

The APN takes a thorough history from each partner. The APN needs to learn how long the couple has been trying to conceive and the results of any previous evaluation to ensure that testing is not repeated unnecessarily.

The woman

A full menstrual history is obtained, including age at menarche, cycle length, characteristics of bleeding, and presence or absence of moliminal symptoms (e.g., bloating, breast tenderness). Absence of moliminal symptoms may suggest anovulation.1 The woman is asked about prior contraception use; her obstetric history, including pregnancy outcomes and complications (e.g., ectopic pregnancy, cesarean delivery, dilation and curettage procedures); past surgeries; current medications; recent weight changes; signs and symptoms of thyroid disease; pelvic or abdominal pain; galactorrhea; hirsutism; and dyspareunia. A history of chlamydia, gonorrhea, or pelvic inflammatory disease (PID) increases the potential for tubal damage and raises suspicion of tubal infertility disease.1,5 

A thorough family history includes a discussion of reproductive outcomes and the existence of birth defects, mental retardation, early menopause, and/or genetic abnormalities.1 The American Congress of Obstetricians and Gynecologists recommends taking a detailed family history and, depending on a woman’s ethnicity, performing preconception carrier screening for cystic fibrosis, sickle cell disease, Tay-Sachs disease, thalassemia, familial dysautonomia, and Canavan disease.6 

The man

Male infertility may be influenced by lifestyle factors (e.g., obesity; use of certain medications, alcohol, or tobacco) or a genetic condition (e.g., cystic fibrosis) or it may be idiopathic. Evaluation begins with a thorough reproductive history to assess for coital frequency and timing, duration of infertility, results of any past evaluations, childhood illnesses (e.g., mumps), systemic illness (e.g., diabetes mellitus, hypertension), past genitourinary surgery (e.g., orchiectomy, hernia repair), sexual history (e.g., erectile dysfunction, history of sexually transmitted infections), and exposure to environmental toxins.7 The history entails a thorough review of systems, a complete family reproductive history, and a social history, including use of recreational drugs, steroids, tobacco, or alcohol (these substances can affect semen parameters).

Physical examination

The woman

The APN performs a targeted physical examination to explore causes of infertility. Weight and body mass index (BMI) are calculated. Ovulatory dysfunction may occur at any BMI level but is more common when it falls outside the healthy range (20-24 kg/m2).1  The thyroid is assessed for enlargement, presence of nodules, or tenderness. Signs of androgen excess (e.g., hirsutism, acne) are noted, as are characteristics of any breast/nipple discharge. Abdominal and bimanual exams are performed to assess for tenderness, organ enlargement, and masses. Pelvic tenderness in the posterior cul-de-sac or uterosacral ligaments may indicate endometriosis. The uterus is palpated for enlargement or immobility, which may indicate fibroids, uterine anomaly, endometriosis, or pelvic adhesions.8 A speculum exam is done to assess the cervix for the presence of abnormalities, secretions, or discharge, which may suggest a pelvic infection.

The man

In the absence of a history of trauma, surgery, genital abnormality, or sexual dysfunction, the physical exam of the man may be deferred pending a semen analysis. An abnormal history or semen analysis finding warrants a physical exam by a urologist or an REI specialist. If a physical exam by the APN is deemed appropriate in a given case, it consists of an inspection of the penis, noting the location of the urethral meatus and the presence of hypospadias; palpation of the testes; ascertainment of the presence and consistency of the vas deferens and the epididymis; and determination of the presence of a varicocele. The APN notes the presence of secondary sex characteristics such as stature, hair distribution, and breast tissue distribution. A digital rectal exam may be considered to evaluate the prostate.1 

Diagnostic testing

Ovulatory function

In order for a woman to conceive, several components are necessary: ovulation, patent Fallopian tubes, a suitable uterine environment, and motile sperm capable of fertilization. Ovulatory dysfunction accounts for up to 40% of female infertility cases and is identified in about 15% of couples.1  Ovulation may be assessed by a mid-luteal progesterone level, an ovulation predictor kit, basal body temperature (BBT) measurements, or mid-cycle ultrasound. In some cases, a menstrual history may be sufficient. If a woman does not have regular and predictable menstrual cycles occurring every 21-35 days, further evaluation is necessary.

A mid-luteal progesterone level is assessed 7 days before expected menses; for a woman with a regular 28-day cycle, progesterone is assessed on cycle day 21.8 For a woman with irregular cycles, this assessment may occur later in the menstrual cycle. A progesterone level greater than 3 ng/mL provides evidence of recent ovulation, although levels greater than 10 ng/mL better reflect good luteal function.9 If the progesterone level is less than 3 ng/mL, the level is rechecked 5-7 days later. If the level remains low, the woman is further evaluated for anovulation.

A woman may choose to use an ovulation predictor kit, also known as a urine luteinizing hormone (LH) kit, to track her ovulation. A woman begins using daily test strips several days before anticipated ovulation to identify the mid-cycle LH surge that precedes ovulation by about 36 hours. The test kit identifies peak fertility as the day of the surge and the following day. The kit is not reliable for all women, particularly those with premature ovarian failure or PCOS, because LH levels may already be elevated.

Although not widely recommended, another option for ovulation detection is the BBT method, an inexpensive way to look retrospectively at the ovulation time frame. An oral temperature is taken at the same time every morning before rising. About 2 days following ovulation, a woman’s temperature rises roughly 0.5° F. Charting this temperature shift can help a woman better identify her ovulation pattern and peak fertility in subsequent months. Of note, evaluating an increase in cervical mucus or using an ovulation predictor kit has been found to be more reliable than BBT in terms of attempting to achieve a pregnancy in the current cycle.10

Ovarian reserve

Oocytes decrease in quantity and quality as women age and are incapable of regenerating. The number of human oocytes peaks at 6-7 million at 20 weeks’ gestation; by the time a female reaches puberty, only 300,000-500,000 oocytes remain. During her lifetime, a woman will ovulate 400-500 eggs. To assess a woman’s fertility potential and determine a treatment plan, the APN must first assess ovarian reserve, which is done by measuring basal follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) levels and performing ovarian imaging early in the follicular phase to evaluate the antral follicle count (AFC).

There is debate regarding the age at which to begin ovarian reserve testing. Current thinking is to recommend such testing for women older than 35 years who have not conceived after 6 months of regular unprotected intercourse.11 The APN may consider testing a woman at an earlier age if certain risk factors are present: anovulation, family history of early menopause, certain genetic conditions such as fragile X or Turner syndrome, history of endometriosis or pelvic infection, previous ovarian surgery, history of cancer treated by gonadotoxic therapy or pelvic radiation, and tobacco use.

Ovarian reserve testing is not infallible and it does not determine the end of a woman’s reproductive capability, nor does it predict the rate in which reproductive potential will diminish. The purpose is to assess the quality and quantity of the remaining oocytes to predict reproductive potential and, for the APN, the time to refer to a specialist. When results fall outside the normal range, the APN can encourage the patient to pursue more aggressive treatment options, which often include referral to an infertility specialist. Ovarian reserve can be assessed by measuring/doing the following:

Basal follicle-stimulating hormone/estradiol

Low estradiol levels early in each menstrual cycle trigger increased secretion of gonadotropin-releasing hormone, leading to increased release of FSH. Then, as the developing cohort of follicles produces estradiol and inhibin B, the increased FSH is suppressed by negative feedback. As a woman ages, a smaller cohort of follicles is available to produce estradiol and inhibin B, which increases secretion of FSH. The robust secretion of FSH stimulates rapid follicular growth and higher estradiol levels, resulting in a shorter follicular phase.11

Estradiol and FSH levels are measured on menstrual cycle days 2-4. FSH values greater than 10 mIU/ mL are associated with diminished ovarian reserve and poor response to ovarian stimulation. Because each menstrual cycle can vary, a single elevated FSH level does not predict an inability to conceive and, therefore, has limited reliability.12 During follicular development, estradiol is released from the developing follicles. In the early follicular phase (typically, cycle day 2-4), the estrogen level is usually less than 50 pg/mL. An elevated value (>60-80 pg/mL) may indicate oocyte depletion.13 For measurements to be meaningful, both FSH and estradiol levels are drawn on menstrual cycle days 2-4.

Clomiphene citrate challenge test

The CCCT may be considered for ovarian reserve testing, although it does not clearly improve FSH and estradiol test accuracy for predicting poor ovarian response or pregnancy after in vitro fertilization (IVF).14 The test requires measurement of cycle day 3 FSH and estradiol levels, followed by administration of clomiphene citrate 100 mg on cycle days 5-9. An FSH level is drawn again on cycle day 10; it should remain below 10 mIU/mL. If either the FSH or the estradiol level on day 3 or the FSH on day 10 is elevated, the patient likely has impaired ovarian function and a referral is warranted. Use of the CCCT has declined because newer tests such as AMH and AFC are simpler and have high predictive values.11

Serum anti-Müllerian hormone

Anti-Müllerian hormone is secreted by the granulosa cells of the pre-antral follicles and is reflective of the primordial oocyte pool.15 As women age and the number of oocytes decreases, the AMH level drops as well. The AMH level may be an earlier predictor of decreased ovarian reserve than FSH levels; it begins to decline early in the ovarian aging process, whereas elevated serum FSH levels are not found until cycles are already irregular.16 The advantage of determining the AMH level is that it remains constant throughout the menstrual cycle and may be drawn at any time.11 Evidence suggests that AMH levels may be diminished with oral contraceptive use and in women with obesity.17 By contrast, women with PCOS have been noted to have AMH levels 2-3 times higher than unaffected women. Overall, an AMH value of 1.0 mg/mL predicts an FSH value of 10.0 mIU/mL. Higher AMH levels suggest normal ovarian function, whereas lower levels have been associated with poor ovarian stimulation and poor pregnancy outcomes.18 Women whose levels fall outside the normal range should be referred to an REI specialist.

Antral follicle count

Ultrasound, although expensive, is another useful tool in evaluating ovarian reserve. AFC is the sum of the antral follicles in both ovaries early in the follicular phase (cycle days 1-4). Antral follicles have been defined as measuring 2-10 mm in diameter. A total of 3-6 antral follicles is considered low, and is associated with poor response in IVF. However, a low value is not predictive of a patient’s ability to conceive.19 No single test has 100% specificity and sensitivity; biochemical assays and imaging should be used in combination to most accurately evaluate ovarian reserve.

Tubal patency

Impaired tubal patency is another common cause of infertility. When tubal disease is suspected by patient history (e.g., chlamydia, gonorrhea, PID, previous ectopic pregnancy, tubal surgery), a hysterosalpingogram (HSG) is considered.8 An HSG can evaluate tubal patency and may have some therapeutic benefit. HSG is typically performed in the late follicular phase, or 2-5 days after the end of menstruation. An HSG can document tubal patency and uterine abnormalities, including filling defects (polyps and fibroids) and uterine malformations (e.g., septum, bicornuate uterus). If an abnormality is noted, a referral is warranted.

Semen analysis

For the male partner, a semen analysis is considered early in the evaluation. This analysis is the most accurate evaluation of male fertility and can be used as a cost-effective way to quickly exclude male factors as the cause of a couple’s infertility. If the semen analysis yields normal results, attention is then focused on the female partner.

Prior to semen collection, the male partner should have an abstinence window of 2-5 days (2-3 days is preferred).20 The analysis may be performed in a fertility center or a urology office where an andrology lab is available. The semen sample is collected in a sterile container provided by the lab. If the man chooses to collect the sample outside the lab, it must be kept warm and delivered within 1 hour of collecting. Normal results for a semen analysis include a volume of 1.5 mL or greater, more than 39 million sperm per ejaculate, total motility of 40%, progressive motility (linear movement) of 32%, and 4% normal forms. If the analysis yields abnormal findings, efforts are made to identify modifiable factors to improve the natural ability of the man’s sperm to fertilize an ovum. Because semen samples can fluctuate, the semen analysis is repeated in 4-6 weeks. If results remain abnormal on repeat evaluation, referral to an infertility specialist is advised.7 

Conclusion

A diagnosis of infertility is life altering for many couples, with lasting psychological impact. The cause of infertility is often multifactorial and complex, leading to frustration in both providers and patients. Because of the substantial emotional, financial, and physical burden to patients, providers must practice with a holistic and therapeutic approach. APNs are in an excellent position to provide this holistic care for their patients, addressing aspects of both physical and emotional well-being. Resources for patients are listed in the Box.

Much of fertility testing is cycle dependent and cannot be completed at a single visit. Therefore, a month or more may be spent completing diagnostic testing before treatment takes place. The APN must assess patient expectations and explain that the evaluation takes time. Once test results are received, the APN may decide to treat with ovulation induction medication (e.g., clomiphene citrate) and timed intercourse for several months or refer to an REI specialist. Because of the length and intimacy of the evaluation, patients may feel more comfortable working with an APN with whom they have already established a trusting relationship before referral to a specialist.

References

  1. Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
  2. Benyamini Y, Gozlan M, Kokia E. Variability in the difficulties experienced by women undergoing infertility treatments. Fertil Steril. 2005;83(2):275-283.
  3. Hull M, Glazener C, Kelly NJ, et al. Population study of causes, treatment, and outcome of infertility. BMJ. 1985;291:1693-1697.
  4. Devine KS. Caring for the infertile woman. MCN Am J Matern Child Nurs. 2003;28(2):100-105.
  5. Akande VA, Hunt LP, Cahill DJ, et al. A cohort study of the prediction of Chlamydia infection causing subfertility, the value of treatment independent management and prognosis for pregnancy in 1119 women following laparoscopy. Presented at: British Congress of Obstetrics and Gynaecology; 2011; Birmingham, UK.
  6. American Congress of Obstetricians and Gynecologists. Preconception Carrier Screening. August 2012.
  7. Practice Committee for the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015;103(3):e18-e25.
  8. Practice Committee for the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2015;103(6):e44-e50.
  9. Quaas A, Dorkras A. Diagnosis and treatment of unexplained infertility. Rev Obstet Gynecol. 2008;1(2):69-76.
  10. Barron ML, Fehring RJ. Basal body temperature measurement: is it useful to couples seeking pregnancy? J Matern Child Nurs. 2005;30(5):290-296.
  11. Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015;103(3):e9-e17.
  12. Kwee J, Schats R, McDonnell J, et al. Intercycle variability of ovarian reserve tests: results of a randomized study. Hum Reprod. 2004;19(3):590-595.
  13. Cahill DJ, Wardle PG. Management of infertility. BMJ. 2002;325(7354):28-32.
  14. Hendriks DJ, Mol BW, Bancsi LF, et al. The clomiphene citrate challenge test for the prediction of poor ovarian response and nonpregnancy in patients undergoing in vitro fertilization: a systematic review. Fertil Steril 2006;86(4):807-818.
  15. Nelson SM. Biomarkers of ovarian response: current and future applications. Fertil Steril. 2013;99(4):963-969.
  16. de Vet A, Laven JS, de Jong FH, et al. Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril. 2002;77(2):357-362.
  17. Kallio S, Puurunen J, Ruokonen A, et al. Antimüllerian hormone levels decrease in women using combined contraception independently of administration route. Fertil Steril. 2013;99(5):1305-1310.
  18. Singer T, Barad DH, Weghofer A, Gleicher N. Correlation of antimüllerian hormone and baseline follicle stimulating hormone levels. Fertil Steril. 2009;91(6):2616-2619.
  19. Hendriks DJ. Mol BW, Bancsi LF, et al. Antral follicle count in the prediction of poor ovarian response and pregnancy after in vitro fertilization: a meta-analysis and comparison with basal follicle stimulating hormone level. Fertil Steril. 2005:83(2):291-301.
  20. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics: Hum Reprod Update. 2010;16(3):231-245.

Web resources (for the Box)

B. reproductivefacts.org/Booklet_Infertility_An_Overview/

C. reproductivefacts.org/FACTSHEET_Diagnostic_Testing_for_Female_Infertility/

D. acog.org/Patients/FAQs/Evaluating-Infertility

E. brighamandwomens.org/Departments_and_Services/obgyn/Services/infertility-reproductive-surgery/infertility-services/education-consent-forms.aspx

F. aafp.org/afp/2015/0301/p308-s1.html

G. cdc.gov/reproductivehealth/Infertility/

Bone densitometry: Performance, interpretation, and clinical application

The authors discuss how to determine who is a candidate for bone densitometry, interpret the results, ascertain when treatment is indicated, and choose among various treatment options.

CASE PRESENTATIONS

You see a 70-year-old mother and her 50-year-old daughter in your practice. You order bone density scans for each of them. Although the scans show that each woman has a T-score of –2.3 at the femoral neck, you will be treating only the older woman with medication.

The daughter underwent a total abdominal hysterectomy 6 months previously and was started on estrogen therapy. She has no history of fracture and reports no use of corticosteroids, no smoking, and minimal intake of alcohol. Pertinent physical examination and laboratory findings are:

• Height, 62 inches; weight, 110 lb;

• Hyperextensible joints;

• Small bone structure;

• Tandem gait excellent; and

• Complete blood count (CBC), complete metabolic panel (CMP), vitamin D, parathyroid hormone (PTH), and 24-hour urinary calcium values all within normal limits.

Based on her FRAX® results (more about this tool later), her 10-year fracture risk is 7.3% for a fragility fracture and 0.5% for a hip fracture. You make sure that she has adequate calcium and vitamin D intake through diet and supplements, and you recommend that she engage in activities that maintain her good balance, engage in weight-bearing exercise, and work out with light weights.

The mother fractured her hip 2 years previously after tripping on a dog toy. She reached menopause at age 45 but chose to forgo hormone therapy. She does not take steroids, smoke, or drink alcohol. Her own mother sustained a hip fracture at age 85. Pertinent physical exam and lab findings are:

• Height, 62 inches; weight, 120 lb;

• Flexibility normal;

• Small bone structure;

• Slight limp from hip fracture;

• Tandem gait done with some difficulty; and

• CBC, CMP, vitamin D, PTH, and 24-hour urinary calcium values all within normal limits.

Based on her FRAX results, her 10-year fracture risk is 35% for a fragility fracture and 14% for a hip fracture. History of a hip fracture alone merits osteoporosis treatment. You recommend adequate calcium and vitamin D intake through diet and supplements, balance training and weight-bearing exercises, and pharmacotherapy with an oral bisphosphonate.

Why did both women undergo bone density scans? And, given the fact that mother and daughter got the same T-score, why is the mother, but not the daughter, a candidate for pharmacotherapy? Some background information is needed to answer these questions.

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of the bone tissue, with a consequent increase in bone fragility that increases the risk for fracture.1 Approximately 10 million persons in the United States have osteoporosis and another 44 million have osteopenia (low bone mass that is less severe than osteoporosis), placing them at increased risk for fracture.2 Fifty percent of women experience an osteoporosis-related fracture in their lifetime, an incidence greater than that of myocardial infarction, stroke, and breast cancer combined.2 Of note, especially for healthcare providers (HCPs) who see young female patients, osteoporosis is not just a disease of bone loss, which commonly occurs as people age. Osteoporosis can also develop in people who do not reach peak bone mass during childhood and adolescence—without the accelerated bone loss that can accompany aging.1

Instead of testing bone strength, which is inappropriate in humans, HCPs can check their patients’ bone mineral density (BMD), which accounts for about 70% of bone strength and serves as a proxy measure for it.1 BMD is ascertained most commonly by dual-energy x-ray absorptiometry  (DXA) of the hip and spine—or in rare cases, the forearm. DXA is used to establish or confirm a diagnosis of osteoporosis, to help predict future fracture risk, and to monitor patients over time, particularly those undergoing osteoporosis treatment.3, 4

Areal BMD can be expressed in absolute terms of grams of mineral per square centimeter scanned (g/cm2) and as a relationship to two norms: the BMD of a young-adult reference population (T-score) and the BMD of an age-, sex-, and race- or ethnicity-matched reference population (Z-score). T-scores and Z-scores are calculated by determining the difference between a patient’s BMD and the mean BMD of the reference population, divided by the standard deviation (SD) of the reference population. Spine and hip BMD measurements in postmenopausal white women are interpreted using the World Health Organization’s T-score definitions of osteoporosis and osteopenia (Table 1).5

Osteoporosis is defined clinically as a fragility fracture of the hip or spine in the absence of other metabolic bone disease, a BMD of –2.5 or lower at any location, or a FRAX score indicating a 10-year risk of a major fragility fracture equal to or greater than 20% or a 10-year risk of hip fracture equal to or greater than 3%.The Fracture Risk Assessment Tool,or FRAX, is a computer-based algorithm that calculates fracture probability from clinical risk factors—age, sex, body mass index, smoking, alcohol use, prior fracture, parental history of hip fracture, corticosteroid use, rheumatoid arthritis (RA), and secondary osteoporosis—and BMD at the femoral neck.8

Fracture

Bone mineral density and fracture risk are inversely related. Each 1 SD decrease in BMD is associated with a 1.6- to 2.6-fold increase in risk of fracture, depending on the skeletal site.Along with low BMD, non-skeletal factors—especially the tendency to fall—contribute to fragility fracture risk. About 90% of fragility fractures occur after falls.10 The pathogenesis of falls in older adults is complex and is related to factors such as age-related deficits in visual, proprioception, and vestibular systems; frailty and de-conditioning; health conditions such as neuropathy, or prior stroke; use of certain medications (e.g., hypnotics, antihypertensives) and polypharmacy; and environmental factors (e.g., poor lighting, loose rugs).11, 12

More than 2 million fragility fractures occur each year in the U.S., accounting for $17 billion in healthcare costs.13 Seventy percent of fragility fractures occur in women. Despite these numbers, fewer than 25% of women aged 67 or older with an osteoporosis-related fracture undergo BMD measurement or begin osteoporosis treatment.12

Vertebral fracture, the most common osteoporotic fracture, may occur in the absence of trauma or after minimal trauma (e.g., bending, lifting).14 Although most vertebral fractures are clinically silent at first, they can eventually cause pain, disability, deformity, and mortality.15 Hip fracture, the most serious consequence of osteoporosis,12 is associated with chronic pain and disability, loss of independence, decreased quality of life, and increased mortality—8% to 36%—within a year.4 More than half of hip fracture survivors cannot live independently; many require longterm nursing home care.16

Although for many years there was awareness of the morbidity and mortality associated with fragility fractures, real progress came only with the ability to diagnose osteoporosis before fractures occur and the development of effective treatments.Measurement of BMD with DXA, which entered routine clinical practice in the late 1980s, has played a vital role in both of these developments. Although BMD correlates with fracture risk, HCPs should keep in mind that most fractures occur in patients with osteopenia. Therefore, patients with osteoporosis or with osteopenia may need treatment.

Osteoporosis workup

According to guidelines published by the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE) in 2016, all postmenopausal women aged 50 years or older should undergo clinical assessment for osteoporosis and fracture risk, starting with a detailed history and physical examination.12 HCPs should check for prior non-traumatic fractures, low body weight (<127 lb), height loss or kyphosis, a family history of osteoporosis and/or fractures, smoking, early-onset menopause, and excessive alcohol intake (3 drinks/day). HCPs should also assess each woman’s risk factors for falling.

The AACE/ACE recommends lateral spine imaging with standard radiography or vertebral fracture assessment (VFA).12 VFA is a method for imaging the thoracic and lumbar spine by DXA for the purpose of detecting vertebral fracture deformities in patients with unexplained height loss, self-reported but undocumented prior spine fractures, or steroid therapy equivalent to 5 mg/day prednisone for 3 months or longer.

The AACE/ACE recommends BMD measurement in women at increased risk for osteoporosis and fractures who are willing to consider pharmacologic treatment if osteopenia or osteoporosis is documented.12 Candidates for BMD measurement include all women aged 65 years or older, as well as younger postmenopausal women who (1) have a history of fracture without major trauma, (2) are on long-term systemic steroids, (3) have radiographic osteopenia, or (4) have clinical risk factors for osteoporosis.12 Three major health organizations—the U.S. Preventive Services Task Force, the National Osteoporosis Foundation (NOF), and the American Congress of Obstetricians and Gynecologists—offer similar screening recommendations.17-19

The AACE/ACE advises that treatment decisions for osteoporosis or osteopenia include consideration of fracture probability.12 Therefore, BMD results should be combined with other clinical risk factors for accurate fracture risk assessment. The FRAX tool can be used to calculate patients’ probability of fracture over 10 years.

In terms of the first question posed at the beginning of this article—Why did both women undergo bone density scans?—the answer is that both the mother and the daughter met criteria for BMD testing: The mother is 70 years old, and the daughter is a 50-year-old postmenopausal woman with low body weight and a mother who sustained a hip fracture.

Management

If postmenopausal osteoporosis is documented based on clinical and imaging fi ndings, HCPs should first ascertain whether it might be secondary to another cause. Certain health conditions that cause or exacerbate bone loss may be asymptomatic and require laboratory testing for detection. Lab tests include a CBC, a CMP, 25-hydroxyvitamin D, PTH, bone-specifi c alkaline phosphatase, and a 24-hour urine collection for calcium and creatinine.12 When indicated, HCPs should address causes of secondary osteoporosis and correct any calcium and/or vitamin D deficiencies. The general approach to management of osteoporosis and osteopenia is as follows:

Nutritional and nonpharmacologic interventions

All women, not just those with low bone mass—should aim for an adequate intake of vitamin D and calcium, participation in weight-bearing and muscle-strengthening exercises, smoking cessation as applicable, minimization of alcohol intake as applicable, and treatment of risk factors for falling. Many scientific organizations recommend an intake of 1,000 IU/day of vitamin D for adults aged 50 or older.12 Serum 25-hydroxyvitamin D levels should be measured in those at risk for vitamin D defi ciency, and vitamin D supplements should be prescribed as needed.4 Adults aged 50 or older are advised to consume 1,200 mg/ day of calcium through diet and a supplement, if needed.20

Measures to reduce falls include individual risk assessment; Tai Chi, yoga for seniors, and other exercise programs; home safety assessment, especially when done by an occupational therapist, and modification as needed; withdrawal of psychotropic medications if possible; and appropriate correction of visual impairment.Measures to be taken inside the home include anchoring rugs, minimizing clutter, removing loose wires, using nonskid mats, installing handrails where needed, adding lighting to stairwells and hallways, wearing sturdy shoes, and avoiding potentially dangerous activities.12

Pharmacotherapy

The AACE and NOF strongly recommend pharmacotherapy for persons with:

• Osteopenia and a history of a fragility fracture of the spine or hip;

• A T-score of –2.5 or lower in the spine, femoral neck, total hip, or distal one-third radius; or

• A T-score between –1.0 and –2.5 in the spine, femoral neck, total hip, or distal one-third radius and a 10-year risk of hip fracture equal to or greater than 3% or a 10-year risk of a major osteoporosis-related fracture equal to or greater than 20%.4,12

In terms of the second question posed at the beginning of this article—Why is the mother, but not the daughter, a candidate for pharmacotherapy?—the answer is that the 50-year-old daughter does not meet criteria for pharmacologic intervention; her BMD is in the osteopenia range, but she has no history of fracture and her FRAX scores do not show a high enough 10-year fracture risk to merit treatment. By contrast, the 70-year-old mother has osteopenia, a personal history of fracture, a maternal history of fracture, and FRAX scores that are high enough to warrant treatment.

Healthcare providers can choose among a variety of medications (Table 2), depending on patients’ health status and fracture risk.4,12 Four agents—alendronate, risedronate, zoledronic acid, and denosumab—have evidence for “broad spectrum” anti-fracture efficacy and are considered initial options in most cases.

Patients with moderate fracture risk, but no fragility fractures, can be started on an oral agent—that is, alendronate or risedronate. Patients with the highest fracture risk are usually started on an injectable such as teriparatide, denosumab, or zoledronic acid. The injectables are also appropriate for patients with upper gastrointestinal (GI) problems who might not tolerate oral medications, those with lower GI problems who might not absorb oral medications, and those with difficulty remembering to take oral medications on a regular basis or coordinating an oral bisphosphonate (BP) with other oral medications or their daily routine.

Bisphosphonates

Three of the aforementioned firstline agents, alendronate, risedronate, and zoledronic acid, are BPs; another member of this class is ibandronate. These agents, which are approved for both prevention and treatment of osteoporosis, have proven anti-fracture efficacy as well; on average, they reduce the incidence of vertebral and hip fractures by 50% over 3 years and they may increase BMD. The major downside is that nearly all oral BP products must be taken on an empty stomach and swallowed with a full glass of water, with at least a half hour intervening before anything other than water is ingested. Many BP users report painful swallowing, nausea, heartburn, or esophageal irritation. Other side effects include hypocalemia; bone, joint, or muscle pain; rash/allergy; and renal dysfunction. Presence of hypocalcemia is a contraindication to BP use. BPs should be used with caution, if at all, in patients with reduced renal function.

Two serious, but rare, adverse effects of long-term BP treatment are osteonecrosis of the jaw (ONJ) and atypical fracture of the femur (AFF). Pain in the thigh or groin area, which can be bilateral, often precedes an AFF. To put the risks of ONJ and AFF in perspective, out of 100,000 postmenopausal women, 50,000 will experience an osteoporosis-related fracture. By contrast, out of 100,000 persons on osteoporosis medication for 5 years, 1 may develop ONJ and 16, AFF.21

Calcitonin

Salmon calcitonin is approved for the treatment of osteoporosis in women who are at least 5 years postmenopausal when alternative treatments are not suitable. Calcitonin reduces vertebral fracture occurrence by about 30% in persons with prior vertebral fractures, but it has not been shown to reduce the risk of nonvertebral fractures and it has only a weak effect on BMD. The most common side effects of nasally administered calcitonin are nasal discomfort, rhinitis, and epistaxis.

Raloxifene

Raloxifene, an estrogen agonist/antagonist, is approved for prevention and treatment of postmenopausal osteoporosis, as well as for the reduction of breast cancer risk. Raloxifene is contraindicated in women of childbearing potential and in those with a history of venous thromboembolism (VTE). Raloxifene has been shown to reduce the risk of vertebral fracture (by 30%-55%), but not nonvertebral fracture or hip fracture. Adverse effects of  this agent include VTE (a 3-fold increased risk, but the absolute risk is low), menopausal symptoms, and leg cramps.

Of note, estrogen therapy is FDA approved only for osteoporosis prevention, not treatment. Likewise, a medication that combines conjugated estrogens with the estrogen agonist/antagonist bazedoxifene is approved to prevent, not treat, osteoporosis after menopause, as well as to treat moderate to severe vasomotor symptoms.

Denosumab

Denosumab, a fully human monoclonal antibody, is approved for treatment of osteoporosis in postmenopausal women at high risk of fracture. This agent decreases bone resorption, increases BMD, and reduces fracture risk by 20%-70% over 3 years, depending on the site. Given subcutaneously (SC) every 6 months, denosumab must be administered by an HCP. Denosumab may be considered for use in certain patients with renal insuffi ciency; impaired renal function does not signifi cantly alter the metabolism or excretion of the drug.22 Denosumab may cause hypocalcemia, which must be corrected before treatment is started. Potential side eff ects include back pain, musculoskeletal pain, cystitis, and hypercholesterolemia. Denosumab has been associated with cellulitis and skin rash, as well as ONJ and AFF in rare cases.

Teriparatide

Recombinant human PTH, or teriparatide, builds bone—as opposed to reducing bone resorption. It is approved for initial treatment of women with postmenopausal osteoporosis who are at high risk of fracture or have failed or been intolerant of previous osteoporosis therapy. Administered SC by patients themselves, teriparatide reduces fracture risk by 50%-65%, depending on the site, after 18 months of therapy. Use of this agent is limited to 2 years. It is contraindicated in patients with pre-existing hypercalcemia, severe renal impairment, or a history of bone metastases or skeletal malignancies, and in those who are at an increased baseline risk for osteosarcoma.23 Potential side effects include orthostatic hypotension, dizziness, myalgias, arthalgias, leg cramps, transient hypercalcemia, increased serum uric acid, hypercalciuria, headache, and nausea.

Monitoring treatment response

After initiating treatment, patients are seen 1-3 months later to check their adherence to the medication regimen and for lab testing. Patients are seen at least yearly to assess their response. Stable or increasing BMD at the spine and hip, as well as no fractures, indicates a satisfactory response.12 Therefore, serial central DXA, performed 1-2 years after initiating therapy and every 2 years thereafter, is a vital component of osteoporosis management. The decision to test BMD every 2 years is based on the time it takes for treatment-related improvement in BMD to occur and on Medicare and health insurance company reimbursement.

Yearly height measurement is also a crucial determinant of osteoporosis treatment efficacy. Patients who lose 2 cm (0.8 in) of height either acutely or cumulatively should undergo repeat vertebral imaging to determine whether new or additional vertebral fractures have occurred since the previous test.4

Duration of pharmacologic treatment

In 2016, the American Society for Bone and Mineral Research issued guidelines for long-term BP treatment.24 The society recommends that, after 5 years of oral therapy or 3 years of IV therapy, HCPs reassess patients’ fracture risk. For women at high risk, HCPs should consider continuing treatment for up to 10 years (oral) or 6 years (IV), with periodic evaluation. Although the risk of AFF, but not ONJ, increases with BP treatment duration, it is outweighed by the benefit of vertebral fracture risk reduction. For women not at high fracture risk, a drug holiday of 2-3 years can be considered after 3-5 years of treatment. By contrast, a drug holiday is not recommended for denosumab users because BMD benefits are rapidly lost with drug discontinuation. Treatment with teriparatide, which is taken for no longer than 2 years, is followed by treatment with an antiresorptive agent to prevent BMD decline and loss of fracture efficacy.

All non-BP osteoporosis medications produce temporary beneficial effects that wane upon discontinuation. By contrast, BPs may allow residual protection against fracture even after treatment cessation. Therapy should be resumed if a fracture occurs, if BMD declines beyond the least significant change (a value computed by each testing facility for relevant measurement sites to determine the magnitude of diff erence that represents a real change), or patients meet initial treatment criteria.

Conclusion

Healthcare providers can decrease postmenopausal patients’ risk of developing osteoporosis and/or experiencing a fragility fracture by clinically assessing them for these risks, ordering radiographic imaging and BMD measurement via DXA as indicated, and prescribing nondrug interventions and pharmacotherapy as needed. Patients who adhere to and tolerate their drug regimens can reduce their fracture risk, depending on the medication and the site, by about half. Patients on osteoporosis medication should be monitored at least once yearly to assess response to treatment, which is gauged by height measurement (every year), BMD via DXA (every 1-2 years), and absence of new fractures.

References

1. National Institutes of Health. Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement; March 27-29, 2000.

2. National Osteoporosis Foundation. Osteoporosis Fast Facts. 2015.

3. Blake GM, Fogelman I. The role of DXA bone density scans in the diagnosis and treatment of osteoporosis. Postgrad Med J. 2007;83(982):509-517.

4. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis Int. 2014;25(10):2359-2381.

5. World Health Organization. Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis: Technical Report Series 843. Geneva, Switzerland: WHO; 1994.

6. Unnanuntana A, Gladnick BP, Donnelly E, Lane JM. The assessment of fracture risk. J Bone Joint Surg Am. 2010;92(3):743-753.

7. FRAX® Fracture Risk Assessment Tool. n.d.

8. Kanis JA, Hans D, Cooper C, et al; Task Force of the FRAX Initiative. Interpretation and use of FRAX in clinical practice. Osteoporos Int. 2011;22(9):2395-2411.

9. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312(7041):1254-1259.

10. Tinetti ME. Clinical practice. Preventing falls in elderly persons. N Engl J Med. 2003;348(1):42-49.

11. Berry SD, Kiel DP. Falls as risk factors for fracture. In: Marcus R, Feldman D, Nelson DA, Rosen CJ, eds. Osteoporosis. 3rd ed. San Diego, CA: Academic Press; 2008.

12. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis – 2016. Endocr Pract. 2016;22(suppl 4):1-42.

13. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465-475.

14. International Osteoporosis Foundation. Vertebral Fracture Initiative. Part I: Overview of Osteoporosis: Epidemiology and Clinical Management.

15. Lewiecki EM, Laster AJ. Clinical review: Clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry. J Clin Endocrinol Metab. 2006;91(11):4215 4222.

16. Orwig DL, Chan J, Magaziner J. Hip fracture and its consequences: differences between men and women. Orthop Clin North Am. 2006;37(4):611-622.

17. U.S. Preventive Services Task Force. Final Recommendation Statement: Osteoporosis: Screening. April 2016.

18. National Osteoporosis Foundation. Bone Density Exam/Testing. 2016.

19. American College of Obstetricians and Gynecologists. Osteoporosis Guidelines Issued. August 21, 2012.

20. Institute of Medicine Committee to review dietary reference intakes for vitamin D and calcium. In: Ross AC, Taylor CL, Yaktine AL et al, eds. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011.

21. Kaiser Permanente. Southern California. Fracture Liaison Service. 2013.

22. Block GA, Bone HG, Fang L, et al. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res. 2012;27(7):1471-1479.

23. Quattrocchi E, Kourlas H. Teriparatide: a review. Clin Ther. 2004;26(6):841-854.

24. Adler RA, El-Hajj Fuleihan G, Bauer DC, et al. Managing Osteoporosis in Patients on Long Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016;31(1):16-35.

Seeing our invisible patients: The importance of providing inclusive sexual and reproductive healthcare to LGBTQ populations

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The author encourages healthcare providers to become more competent and inclusive in caring for patients who identify as lesbian, gay, bisexual, transgender, or gender-queer or non-conforming.

Statement of the problem

Women who identify as lesbian or bisexual (also known as sexual minority women, or SMW), as well as those who were assigned female gender at birth but identify as transgender, gender-queer, or gender non-conforming (TQ), represent subsets of the LGBTQ population. These groups have historically experienced discrimination and stigma in healthcare. As a result, they may be less likely than heterosexual women or cis-gender women (those whose gender identity matches the female sex they were assigned at birth) to seek sexual and reproductive healthcare. Even if they seek this type of care, they may not be properly assessed, managed, or educated if their healthcare providers (HCPs) lack the knowledge and communication skills they need to provide inclusive sexual and reproductive care to SMW and TQ patients. In a video from the National LGBT Education Center, LGBT individuals share some of the experiences, both bad and good, that they have had with HCPs.

Dearth of research

Perpetuating this healthcare disparity is a dearth of research on LGBTQ-specific healthcare needs (with the exception of HIV/AIDS and mental health problems in gay men). Only in the past 5 years have the many health disparities experienced by LGBTQ individuals and the need for LGBTQ-specific research become a topic of conversation on a national level. From 1989 until 2011, 0.5% of studies funded by the National Institutes of Health (NIH), the largest funder of medical research in the world, pertained to LGBTQ health, and of that 0.5%, only 13.5% was allocated to SMW and 0.2% to transgender men.1 In 2011, the CDC identified health disparities related to sexual orientation as one of the main gaps in current health disparities research.2 In the same year, the Institute of Medicine reported the inadequacy of LGBTQ health research, identified challenges in conducting research on these populations, and established recommendations for the NIH, including implementation of a research agenda designed to advance knowledge and understanding of LGBTQ health.3

Dearth of educational programs

The curricula in most clinical education programs do not include adequate LGBTQ-related content. One study that specifically assessed inclusion of LGBTQ-related content in medical school curricula in the United States and Cana da found, on average, 5 hours of instruction in this area.Although corresponding studies assessing nursing school curricula have not been reported, they would likely reveal similarly discouraging findings. Educating future HCPs, through both classroom instruction and clinical experiences, to care for LGBTQ patients will help increase the number of HCPs who are competent and comfortable in this area.

Ways to provide competent and inclusive healthcare for LGBTQ populations

As a basic foundation in this regard, HCPs must understand the differences among the terms sex assigned at birth, sexual orientation, and gender identity. Sex assigned at birth, also referred to as biological sex, is based objectively on genital appearance, hormones, and chromosomes. Sexual orientation refers to the object of a person’s physical and/or emotional attraction. Gender identity represents how one perceives oneself—as female, as male, or somewhere in between.

Both U.S. society and the healthcare community within it are hetero-normative and cis-normativeinadvertently creating an environment that is a source of implicit discrimination toward LGBTQ populations.In a heteronormative society, heterosexuality is the expected and “normal” sexual orientation. Similarly, in a cis-normative society, being cis-gender—having a gender identity that matches one’s sex assignment at birth—is expected and “normal.” By these definitions, anyone who lives/behaves as anything other than heterosexual or who identifies as anything other than cisgender is considered “abnormal.”

Recognize and aim to overcome health disparities

Although the literature has been sparse, newly emerging studies provide information about the sexual and reproductive health behaviors of young SMW populations. In general, researchers have found that SMW (and/or sexual minority teens), compared with their heterosexual counterparts:

• display a greater number and range of sexually risky behaviors (e.g., younger age at sexual debut, greater number of sex partners, greater use of alcohol or drugs during sexual encounters, greater likelihood of having unprotected sex)6-11;

• with the exception of lesbians11 have higher rates of sexually transmitted infections (STIs)7,8,10;

• have similar rates of unwanted pregnancy and higher rates of abortion6,8,10;

• have lower rates of contraceptive and gynecologic care seeking, including a lesser likelihood of getting Pap tests and the HPV vaccine series12-15;

• have a greater likelihood of being subjected to intimate partner violence (IPV)6-8; and

• may have an elevated risk for breast cancer because of their increased rate of nulliparity, older age at first live birth, and greater rates of obesity and alcohol consumption.16

Fewer studies have addressed the sexual and reproductive health disparities that affect TQ populations, which also include gender non-binary individuals, who reject the assumption that gender is strictly an either/or option of male/female that matches the sex they were assigned at birth.17 Instead, these individuals view gender identity as a spectrum of possibilities. No epidemiologic studies on transgenderism in the U.S. have been published, and demographic studies based on national surveys have been limited because of a lack of questions about gender identity.18

About 0.3% of adults in the U.S. (~1 million persons) are thought to identify as transgender.18 Most of the available literature concerns transgender females (i.e., persons who are assigned the male sex at birth but who identify as female). In studies conducted in countries outside the U.S., the prevalence of transgender males (i.e., persons who are assigned the female sex at birth but who identify as male) has been reported as 1:30,400 to 1:200,000.19

Many transgender individuals have experienced discrimination in healthcare, particularly after disclosing their gender identity to their HCP. Experiences of hostility and/or insensitivity from their own HCP can cause mistrust of HCPs in general.20 This cycle can lead to a lack of utilization of healthcare services, particularly when care is not critical for survival.

Despite the lack of research, transgender males do express concerns related to their sexual and reproductive healthcare, particularly with respect to discrimination, lack of validation of their gender identity, physical discomfort during examinations, fertility preservation, and pregnancy. Another fact to keep in mind: Although a person born with a uterus and ovaries may not identify as female, this person may wish to have biological children. In a cross-sectional Web-based survey of transgender males who had been pregnant and delivered a baby, two-thirds of the pregnancies were planned, and pregnancy, delivery, and birth outcomes did not differ according to whether or not the patient had used testosterone prior to pregnancy.21

Avoid faulty assumptions

Not all patients are heterosexual and cis-gender. If a reproductive-aged patient states that she is sexually active, an HCP should not necessarily follow up with the question “What type of birth control are you using?” First, the HCP needs to determine the patient’s sexual orientation; she may not need to practice birth control. Instead of giving patients two gender options—“male” and “female”—on intake forms, the HCP can provide a box labeled “other” that can be filled in with the patient’s stated identity.

These concepts also apply to the way that visit types are labeled in the office. Visits related to contraception care are often termed family planning visits, and those that occur yearly are often termed well-woman exams. The terminology for these visit types can be off-putting to persons, including staff members, who may not use contraceptives for birth control and for those who may not identify as women even though they have female genitalia and reproductive organs. HCPs should aim to create an inclusive office atmosphere so that SMW and TQ patients can build trust in their provider and receive healthcare that meets their needs.

Create an inclusive environment

Providers should not assume that a patient coming into the office for contraceptive care or for a yearly checkup is heterosexual and cis-gender. One of the first things any patient does in an office visit is complete intake and health history forms. Forms are more inclusive when the term partner or spouse is used instead of husband or wife and when transgender and other identitywith a write-in area, are added to the cis-gender options of male and female. HCPs need to ask patients who identify as transgender, gender-queer, or gender non-conforming about their preferred names and which gender pronouns they use (e.g., he, she, they). Preferred names may differ from the legal documentation on their driver’s licenses and insurance cards; HCPs must avoid using a name that the patient no longer uses or that may cause distress. Questions about preferred names and gender pronouns are appropriate and polite, and demonstrate from the outset of the professional relationship that the HCP and the staff acknowledge and validate all their patients’ sexual orientations and gender identities.

Non-discrimination policies need to be posted in check-in areas and/or waiting rooms where they are easily visible. Information about and examples of patient non-discrimination policies are available through the Human Rights Campaign Healthcare Equality Index website. Staff members need to know these policies and adhere to them. After all, the first person with whom a patient has contact in a healthcare setting is usually not the HCP but, rather, the office reception staff. The National LGBT Health Education Center, a program of The Fenway Institute, offers online webinars and video training sessions that can be used to help educate clinical and administrative office staff members.

Follow health screening and preventive health recommendations

Recommendations are implemented for SMW and TQ patients within the same parameters as for heterosexual and cis-gender female patients. Screening for STIs and HIV is based on behaviors and risk factors, not on sexual orientation or gender identity. HCPs need to ask patients about the types of sexual behaviors in which they engage so that the types of STI screenings and the sites of sampling can be determined. HCPs also need to advise patients to catch up on their HPV vaccinations if they have not completed them.

Providers need to ask patients whether they have a partner with whom it would be possible to get pregnant, and whether they are having penetrative vaginal sex with this partner. If so, and if the patient does not desire a pregnancy, HCPs need to discuss and offer all available and appropriate contraceptive options. HCPs need to inform SMW and TQ patients that, even if they are not engaging in what is typically considered heterosexual or cis-normative sex, they could still be at risk for cervical dysplasia or cancer and should undergo cervical cancer screening according to current guideline recommendations. Screening for a history of or current IPV needs to be included.

Clinical breast exams need to be performed and screening mammography recommendations followed, even in patients who have had “top surgery” or a bilateral mastectomy because these individuals may have residual breast tissue. Because this topic may be a sensitive one, HCPs must allow adequate time to communicate openly and compassionately about it.

Enhance competence and understanding

Conferences and webinars on providing healthcare to LGBTQ patients, many with continuing education credit, are available from organizations such as the World Professional Association for Transgender Health, UCSF Center of Excellence for Transgender Health, The Fenway Institute, and Health Professionals Advancing LGBT Equality (formerly the Gay and Lesbian Medical Association). These organizations and others have developed vetted lists of articles, publications, and online training sessions that can be used as resources (Table). For HCPs seeking more intensive education in LGBTQ health, graduate certificate programs are available through institutions such as Drexel University in Philadelphia, The George Washington University in Washington, DC, and New York University in New York City.

Conclusion

Healthcare providers who manage the sexual and reproductive health concerns of heterosexual and cisgender women are used to providing sensitive and compassionate care during vulnerable stages throughout the lifespan. They need to expand their knowledge and understanding, and acknowledge their implicit assumptions and biases, if they exist, in order to provide the same quality of care to SMW and TQ patients. These populations are often overlooked or “invisible” in healthcare settings, or they experience discrimination, stigma, and hostility, precluding their full access to and utilization of routine and preventive care.

Nationally representative research is needed to fully reveal the health disparities and risk factors that burden these populations. Curricula must be expanded to prepare future HCPs to adequately address these concerns and provide competent and inclusive sexual and reproductive healthcare. HCPs need to use available evidence, create inclusive office environments, and commit to continuing education that expands knowledge about LGBTQ healthcare needs for themselves and their staff to help make a meaningful difference and have a beneficial effect in caring for these populations.

References

1. Coulter RWS, Kenst KS, Bowen DJ, Scout. Research funded by the National Institutes of Health on the health of lesbian, gay, bisexual, and transgender populations. Am J Public Health. 2014;104(2):e105-e112.

2. CDC. CDC Health Disparities and Inequalities Report – United States, 2011. MMWR Suppl. 2011;60(1):1-2.

3. The National Academies Press. The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding. March 31, 2011.

4. Obedin-Maliver J, Goldsmith ES, Stewart L, et al. Lesbian, gay, bisexual, and transgender-related content in undergraduate medical education. JAMA. 2011;306(9):971-977.

5. Morrison S, Dinkel S. Heterosexism and health care: a concept analysis. Nurs Forum. 2012;47(2):123-230.

6. Tornello SL, Riskind RG, Patterson CJ. Sexual orientation and sexual reproductive health among adolescent women in the United States. J Adolesc Health. 2014;54(2):160-168.

7. Oshri A, Handley ED, Sutton TE, et al. Developmental trajectories of substance use among sexual minority girls: associations with sexual victimization and sexual health risk. J Adolesc Health. 2014;55:100-106.

8. McCauley HL, Silverman JG, Decker MR, et al. Sexual and reproductive health indicators and intimate partner violence victimization among female family planning clinic patients who have sex with women and men. J Womens Health (Larchmt). 2015; 24(8):621-628.

9. Matthews AK, Cho YI, Hughes T, et al. The relationships of sexual identity, hazardous drinking, and drinking expectancies with risky sexual behaviors in a community sample of lesbian and bisexual women. J Am Psychiatr Nurses Assoc. 2013;19(5):259-270.

10. Herrick A, Kuhns L, Kinsky S, et al. Demographic, psychosocial, and contextual factors associated with sexual risk behaviors among young sexual minority women. J Am Psychiatr Nurses Assoc. 2013;19(6):345-355.

11. Estrich CG, Gratzer B, Hotton AL. Differences in sexual health, risk behaviors, and substance use among women by sexual identity: Chicago, 2009-2011. Sex Transm Dis. 2014; 41(3):194-199.

12. Lindley LL, Barnett, CL, Brandt HM, et al. STDs among sexually active female college students: does sexual orientation make a difference? Perspect Sex Reprod Health. 2008; 40(4):212-217.

13. Waterman L, Voss J. HPV, cervical cancer risks, and barriers to care for lesbian women. Nurse Pract. 2015; 40(1):46-53.

14. Charlton BM, Corliss HL, Missmer SA, et al. Influence of hormonal contraceptive use and health beliefs on sexual orientation disparities in Papanicolaou test use. Am J Public Health. 2014;104(2):319-325.

15. McRee A-L, Katz ML, Paskett ED, Reiter PL. HPV vaccination among lesbian and bisexual women: findings from a national survey of young adults. Vaccine. 2014;32(37):4736-4742.

16. Clavelle K, King D, Bazzi AR, et al. Breast cancer risk in sexual minority women during routine screening at an urban LGBT health center. Womens Health Issues. 2015;25(4):341-348.

17. Green ER, Maurer, L. Teaching Transgender Toolkit: A Facilitator’s Guide to Increasing Knowledge, Decreasing Prejudice and Building Skills. Ithaca, NY: Planned Parenthood of the Southern Finger Lakes; 2015.

18. Stroumsa D. The state of transgender health care: policy, law, and medical frameworks. Am J Public Health. 2014;104(3):e31-e38.

19. World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, Version 7.

20. Bradford J, Reisner SL, Honnold JA, Xavier J. Experiences of transgender- related discrimination and implications for health: results from the Virginia Transgender Health Initiative Study. Am J Public Health. 2013; 103(10):1820-1829.

21. Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014;124(6):1120-1127.

Web resources (Table)

E. lgbt.ucsf.edu/lgbt-education-and-training

F. http://transhealth.ucsf.edu/

G. glma.org/index.cfm?fuseaction=Page.viewPage&pageId=534

H. fenwayhealth.org/the-fenway-institute/

I. mazzonicenter.org/training-and-resources

J. straightforequality.org/Healthcare

K. wpath.org/site_page.cfm?pk_association_webpage_menu=2577&pk_association_webpage=6633

L. hrc.org/hei/the-national-lgbt-health-education-center#.VttJLVKzWu4

Interventions to increase LARC acceptances, with a focus on IUCs

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Long-acting reversible contraceptives, or LARC, are growing in popularity because they are highly effective, safe, and well tolerated. In addition, LARC methods require virtually no effort on the part of users besides seeing their healthcare provider (HCP) for insertion and removal. The authors describe their experience in “getting to yes”—that is, in encouraging HCPs to offer LARC methods in a patient-friendly environment and patients to consider using them—so that teens and women have access to all methods, autonomy over their method decision, and decreased risk of unintended pregnancy.

Key words: long-acting reversible contraceptives, LARC, intrauterine contraceptive, IUC, IUD, LNG-IUS

Of the 6.1 million pregnancies in the United States each year, 45% are unintended—either mistimed (27%) or unwanted (18%).1,2 Ninety-five percent of unintended pregnancies occur in females who do not use contraceptives (54%) or who use them inconsistently (41%).These unintended pregnancies may end in abortion (42%) or birth (58%),both of which have socioeconomic, fiscal, and health-related consequences. Births resulting from unintended or closely spaced pregnancies can have a variety of adverse maternal and child health outcomes.1 Furthermore, females who have children before they are ready are less likely to reach their educational, career, financial, and/or family-related goals.

Unintended pregnancies can be avoided by correct and consistent use of a birth control method. Among all reversible methods, those that require the least amount of effort by the user have been demonstrated to be the most effective at pregnancy prevention.

Background information on LARC

Long-acting reversible contraceptives, or LARC, include the subdermal implant and intrauterine contraceptives (IUCs).Both implants and IUCs are highly effective in preventing pregnancy and are FDA-approved for 3-10 years of use. In addition, these methods are reversible and do not impair fertility once they are removed; users who wish to become pregnant can have them removed at any time. LARC methods are the most effective forms of reversible birth control available: During the first year, fewer than 1% of implant or IUC users will become pregnant.4 Failure rates associated with the use of other contraceptives are considerably higher.

Devices

The implant is a single, matchstick-sized, etonogestrel-containing rod that is placed in the subdermal tissue of the inside aspect of the upper non-dominant arm.5 The implant, which is marketed as Nexplanon®, contains barium, allowing localization with radiography. The implant is FDA-approved for 3 years of use.

Intrauterine contraceptives, either an intrauterine device (IUD) or an intrauterine system (IUS), are T-shaped devices containing copper or levonorgestrel (LNG).Four IUCs are available, the Copper T 380A (ParaGard®) and three LNG-IUS products: Mirena®, Skyla®, and Liletta®. The copper IUD is effective immediately following placement7 and is FDA approved for 10 years of use.Mirena is FDA approved for 5 years of use, and Skyla and Liletta for 3 years of use.6 Data collection for Liletta is ongoing; it is expected that the manufacturer will ultimately seek approval for up to 7 years of use. If an LNG-IUS product is placed during the first 7 days of the menstrual cycle or immediately following birth, a miscarriage, or a first-trimester abortion, then back-up contraception is not needed.6,8 Otherwise, a backup method is recommended for the first 7 days.

Of note, LARC methods do not protect users against sexually transmitted infections (STIs). Condoms are needed for protection against STIs.

Medical eligibility criteria

All teenagers and women should be considered candidates for LARC use until proven otherwise.9-11 Readers can access the CDC’s Summary Chart of U.S. Medical Eligibility Criteria for Contraceptive Use. Information from the CDC is also available as a free iPhone or iPad app at the iTunes store or as an eBook available on an eReader app.

Trends in LARC use

LARC methods are gaining in popularity for many reasons, but mainly because of their high efficacy.12 According to an analysis of National Survey for Family Growth (NSFG) data, the proportion of female U.S. contraceptors using the IUD or implant increased from 2.4% in 2002 to 3.7% in 2007 and to 8.5% in 2009.13 According to a more recent analysis of the NSFG data, the prevalence of LARC use among contraceptors rose from 8.5% in 2009 to 11.6% in 2012, a significant increase.14,15 Much of this trend was driven by IUC use, which increased from 7.7% to 10.3%; implant use remained low (1.3%) and did not change significantly between these two time periods.

The Contraceptive CHOICE Project

Although increased use of LARC methods has been encouraging, uptake is still relatively low—especially considering the high rate of unintended pregnancy in this country, the superior efficacy of these methods, and the many non-contraceptive benefits they offer. The next logical question is, What can be done to increase education about and access to LARC methods for reproductive-aged females who wish to prevent pregnancy?

Purpose and methods

The Contraceptive CHOICE Project was undertaken to remove educational, financial, and access barriers to contraception; to promote the most effective methods of birth control; and to reduce unintended pregnancy in the St. Louis, Missouri, area.16 Objectives of the project were to increase uptake of LARC; to measure/analyze method choice, satisfaction, side effects, and continuation across all reversible contraceptive methods; and to provide enough no-cost contraception to exert a population impact on unintended pregnancies particularly with respect to teen pregnancy and repeat abortion.

Enrollment began in August 2007 and ended in September 2011. Prospective enrollees ranged in age from 14-45 years, wanted to avoid pregnancy for ≥1 year, and were willing to initiate a new form of reversible contraception.17,18 Recruitment was done via word of mouth, referral from private and community healthcare providers (HCPs), and from the two abortion facilities in the St. Louis region. Participants underwent standardized evidencebased contraceptive counseling by trained non-clinicians. The counseling was structured on effectiveness tiers, and included the risk and benefits of each method. Tier 1 contraceptives—the most effective methods, which include LARC (IUCs and the implant)— were described first. Next, the counselor described tier 2 methods or refillables: depot medroxy-progesterone acetate (DMPA), and the pill/patch/ring (PPR). Tier 3 methods, including the diaphragm, the condom, the sponge, spermicide, withdrawal, and fertility awareness-based methods, were described last. Participants received their chosen contraceptive free of charge, and they could switch methods as frequently as they wanted for the duration of their study participation (2-3 years).

Results

Contraceptive choices of the entire cohort and of the teen cohort alone are shown in the FigureAmong 9,256 adult and teen participants, 75% chose a LARC method; among teens alone, 71% chose a LARC method.

Continuation rates

Among LARC users, adults and teens had high continuation rates—87% and 82%, respectively— at 12 months.19,20 Non- LARC users had much lower 12- month continuation rates: 59% for adults and 49% for teens. Among LARC users, continuation rates at 24 months were still high: 78% for adults and 67% for teens.20 Only 42% of adult non-LARC users and 37% of teen non-LARC users continued using the contraceptive method they chose at baseline for 24 months. At 3 years, continuation rates were 67.2% among LARC users and 31.0% among non-LARC users.21

Satisfaction levels

Twelve-month satisfaction levels mirrored continuation rates. A greater proportion of LARC users than non-LARC users reported being very satisfied or somewhat satisfied with their method (81.2% vs. 48.8%).19 This differential in satisfaction between LARC users and non-LARC users held true for adults (82% vs. 50%) and for teens (75% vs. 42%). Satisfaction was similarly high among users of the subdermal implant, copper IUD, or LNG-IUS (range, 72% for teen users of the copper IUD to 84% for adult users of the LNG-IUS) and similarly low among users of DMPA or PPR (range, 31% for teen users of the ring to 52% for adult users of DMPA or the ring).

Unintended pregnancy and abortion rates

Even more important, among 7,486 participants included in this analysis, 334 (4.5%) experienced unintended pregnancies.4 Failure rates among PPR users were 4.8%, 7.8%, and 9.4% in years 1, 2, and 3, respectively; corresponding rates among LARC users were 0.3%, 0.6%, and 0.9%
(P <.001). Failure rates among DMPA users were similar to those of the LARC users. LARC methods were highly effective in preventing pregnancy regardless of a user’s age, whereas teen PPR users were twice as likely as adult PPR users to become pregnant.

One of the primary outcomes of interest was the percentage of abortions that were repeat abortions.18 Using vital statistics data from Missouri’s state health department, the investigators found a significant difference in the proportion of repeat abortions between the St. Louis region and Kansas City in 2009 (respective rates, 46% vs. 49%; P = .02) and 2010 (respective rates, 44% vs. 51%; P <.01). In addition, they detected a significant decline in the proportion of repeat abortions over time in the St. Louis region (= .002). Another analysis revealed that pregnancy, birth, and abortion rates among teens in the CHOICE Project were substantially lower than national rates among sexually experienced teens.22 Respective annual rates of pregnancy, birth, and abortion were 34.0, 19.4, and 9.7 per 1,000 teen CHOICE Project participants, as compared with 158.5, 94.0, and 41.5 per 1,000 sexually experienced U.S. teens in 2008.

Summary of main findings

LARC methods, as compared with shorter-acting methods, were associated with higher continuation rates and user satisfaction levels, regardless of age. In addition, LARC methods were associated with lower rates of unintended pregnancy and, as a consequence, lower rates of birth and abortion. An informative video about the Contraceptive CHOICE Project is available at Pathway to Choice. Box 1 shows how CHOICE got to yes.

Barriers to IUC use, and how to overcome them

In order for the encouraging results of the CHOICE Project to translate to other populations throughout the country, barriers must be overcome. From this point onward, this article focuses on IUCs.

The National Committee for Quality Assurance has issued a White Paper, Women’s Health: Approaches to Improving Unintended Pregnancy Rates in the United States, that describes numerous barriers that impede our nation’s ability to reduce the rate of unintended pregnancy. To read a summary of these barriers, click here. To read the entire White Paper, click here.

Provider barriers

Many HCPs have concerns about prescribing and placing IUCs. Many of these concerns are easily addressed.

Lack of training

If an HCP’s training occurred prior to 2001, she or he may not have received instruction in IUC placement. To acquire such training, HCPs can seek out instructors provided by product manufacturers or academic institutions, or they can attend conferences where such training is provided. HCPs need not be certified by the manufacturer to place IUCs; any HCP who feels comfortable with the instructions and the procedure may place them.

Too few patients to gain competency

An HCP such as a primary care provider or a rural health provider may not see enough patients to maintain a comfortable competency in IUC placement. This barrier may or may not be surmountable; each HCP has her or his own threshold for a feeling of competency. One approach is to form a collaborative relationship with a high-volume provider who can offer ongoing support and training. In addition, if HCPs view each patient encounter with a reproductive-aged female as an opportunity to address her goals with respect to pregnancy and/or pregnancy prevention, then they will likely be providing many more contraceptive services than they think.

Fear of litigation

Some HCPs may fear litigation if complications arise; some of the items in the bulleted list in the next section can help dispel this fear. Concerns based on myths Each of these myths surrounding IUCs is debunked.

Teenagers and nulliparous women are not appropriate candidates for IUCs. Evidence shows that these females are excellent candidates for IUCs, which are highly effective regardless of age or parity.10

Young women won’t like IUCs because placement is too painfulPlacement comfort varies from patient to patient. Many young women tolerate the placement procedure very well.23

Most patients cannot afford IUCsMany women have coverage for IUCs.24 More will be able to get them as the Affordable Care Act (ACA) continues to implement the 2011 Institute of Medicine recommendations.

Women should have IUC counseling at one visit and return for IUC placement at the next visitTwo-thirds of women prefer to have the IUC placed on the same day it is prescribed.25 Adding a second visit places an extra barrier between the patient and her receiving the desired contraceptive, thereby increasing her risk for unintended pregnancy.

Patients won’t keep their IUCsIUCs had the highest continuation rates of any method offered in the CHOICE Project.26

Patients already know what they want. When CHOICE Project participants were advised of all their birth control options and allowed to choose what they wanted, 58% chose an IUC. In the real world, only 10% of U.S. females choose an IUC.14,15 Many females are unfamiliar with LARC methods or harbor misconceptions about them. They cannot know what they want unless they are fully informed about the options.

HCPs don’t have time to tell patients about every methodTrained staff members can inform patients of their options, starting with the most effective methods.27 In addition, HCPs can provide decision aids that patients can use in the waiting room before their visits.

High upfront cost

The high cost to stock IUCs, with a delay in reimbursement, may keep some HCPs from offering them. The ACA has helped in that the cost of a contraceptive and its placement should be fully covered, with no cost share to the patient. However, barriers do remain: Some health insurance plans exclude contraceptive coverage for religious reasons, small companies need not comply, and some state plans do not cover at 100% or have restrictions on use.

Concern about a prospective IUC user being pregnant 

According to the U.S. Selected Practice Recommendations for Contraceptive Use, an HCP can be reasonably certain that a patient is not pregnant if she has no signs or symptoms (S/S) of pregnancy, has a negative urine pregnancy test result, and meets any one of these criteria8:

• ≤7 days after the start of her normal menses;

• abstinence since the start of her last normal menses;

• correct and consistent use of contraception;

• ≤7 days after spontaneous or induced abortion;

• within 4 weeks postpartum; or

• fully or nearly fully breastfeeding, amenorrheic, and <6 months postpartum.

Concern about a prospective IUC user having an STI

At-risk patients can be tested for gonorrhea and chlamydia at IUC placement.10 If a positive result is noted, the device can still remain in place. The HCP can treat the infection, offer expedited partner therapy as per CDC guidelines, inform patients about the warning S/S of pelvic inflammatory disease (PID; e.g., new-onset abdominal or pelvic pain, foul-smelling vaginal discharge, pain during or shortly after sex, fever, abnormal uterine bleeding), and retest in 3 months. However, if an HCP suspects active infection at the time, the device should not be placed. Instead, the patient is tested and treated as needed. No evidence suggests that IUCs increase the risk for developing an STI.

Patient barriers

These barriers include lack of knowledge about IUCs, negative influence of friends or the media, lack of access to HCPs who can provide IUCs, and cost concerns. The CHOICE Project overcame these barriers by having non-clinicians educate participants about all birth control methods. HCPs provided same-day LARC placement as per the U.S. Selected Practice Recommendations for Contraceptive Use guidelines.The birth control methods were provided free of charge. In Open the Dialogue, CHOICE Project participants describe how they felt when education, access, and cost barriers were removed and they could choose any birth control method they wanted.

IUC risks and side effects

One of the main concerns about IUC placement is uterine perforation, which occurs in about 1 in 1,000 placements.3 Red flags indicating acute uterine perforation include the uterus sounding to a depth greater than that appreciated on bimanual examination, sudden loss of resistance, and patient pain disproportionate to that expected. Vaginal bleeding is unlikely.

Another concern is PID, which develops in fewer than 1% of IUC users, usually during the first 20 days post-placement. Appropriate precaution—screening highrisk women at the time of placement and delaying placement in those with active cervicitis—is the best way to minimize this risk. In very rare cases, pregnancy may occur with the IUC in place; if so, there is a higher chance that it will be an ectopic pregnancy. IUC users with a positive pregnancy test result need to be promptly evaluated to rule out ectopic pregnancy and undergo pregnancy options counseling.

With the copper IUD, menstrual pain and bleeding may increase at first.3 Intermenstrual bleeding may occur as well. These side effects are common in the first few months of use and tend to subside within a year. The LNG-IUS may be associated with spotting, irregular bleeding, and menstrual cramping in the first few months of use. Again, these side effects tend to diminish over time. Some users may experience LNG-related effects such as headache, nausea, depression, and breast tenderness.

Creating a LARC-friendly practice

Healthcare providers who wish to create a LARC-friendly practice know that LARC methods are the most effective reversible methods. They know that every patient is a LARC candidate until proven otherwise. They have ensured that all office staffers are knowledgeable about LARC, can follow an effectiveness tier-based counseling approach as per the CDC guidelines, and promote LARC use. After all, support staff members’ perceptions can greatly affect patients’ decisions. Other tenets of a LARC-friendly practice include the following:

• Every effort is made to help patients obtain the method of their choice.

• Same-day LARC placement is the standard.

• All HCPs have received proper LARC training.

• LARC methods are stocked if possible.

More information about setting up a LARC-friendly practice, including an introductory video, is available at the LARC First website. A message from the authors appears in Box 2.

Conclusion

Long-acting reversible contraceptives are the most effective birth control methods on the market. As shown in the CHOICE Project, IUCs and implants are superior to other methods in terms of continuation rates and satisfaction levels. As such, LARC methods should be considered first-line options for all females, including adolescents and nul liparous women. LARC method efficacy does not depend on user compliance. HCPs should provide counseling and reassurance so that patients know what to expect at the time of placement, as well as possible side effects. Same-day IUC placement should be the standard. As providers of healthcare to teenage girls and women, HCPs are privileged to be able to have a dramatic impact on patients’ lives with such a simple intervention.

References

1. Guttmacher Institute. Unintended Pregnancy in the United States. Fact Sheet. March 2016.

2. Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008–2011. N Engl J Med. 2016;374(9):843-852.

3. American Congress of Obstetricians and Gynecologists. Long-Acting Reversible Contraception (LARC): IUD and Implant. May 2016.

4. Winner B, Peipert JF, Zhao Q, et al. Effectiveness of long-acting reversible contraception. N Engl J Med. 2012;366(21):1998-2007.

5. Association of Reproductive Health Professionals. Choosing a Birth Control Method. Implant. Updated June 2014.

6. Association of Reproductive Health Professionals. Choosing a Birth Control Method. Intrauterine Contraception. Updated June 2014.

7. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83(5):397-404.

8. Centers for Disease Control and Prevention. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. July 29, 2016.

9. ACOG Practice Bulletin. Long-Acting Reversible Contraception. #121, July 2011.

10. CDC. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. July 29, 2016.

11. MacGregor KE, Khadr SN. Contraception for adolescents (American Academy of Pediatrics). Arch Dis Child Educ Pract Ed. 2016;101(2):61-64.

12. Branum AM, Jones J, for the Centers for Disease Control and Prevention. Trends in Long-acting Reversible Contraception Use Among U.S. Women Aged 15–44. NCHS Data Brief No. 188, February 2015.

13. Finer LB, Jerman J, Kavanaugh MLO. Changes in use of long-acting contraceptive methods in the United States, 2007-2009. Fertil Steril. 2012;98(4):893-897.

14. Kavanaugh ML, Jerman J, Finer LB. Changes in use of long-acting reversible contraceptive methods among U.S. women, 2009-2012. Obstet Gynecol. 2015;126(5):917-927.

15. Guttmacher Institute. Use of Long-Acting Reversible Contraceptive Methods Continues to Increase in the United States. Press release. October 8, 2015.

16. Contraceptive CHOICE Project.

17. Secura GM, Allsworth JE, Madden T, et al. The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception. Am J Obstet Gynecol. 2010;203(2):115.e1-7.

18. Peipert JF, Madden T, Allsworth JE, Secura GM. Preventing unintended pregnancies by providing no-cost contraception. Obstet Gynecol. 2012;120(6):1291-1297.

19. Rosenstock JR, Peipert JF, Madden T, et al. Continuation of reversible contraception in teenagers and young women. Obstet Gynecol. 2012;120(6):1298-1305.

20. O’Neil-Callahan M, Piepert JF, Zhao Q, et al. Twenty-four-month continuation of reversible contraception. Obstet Gynecol. 2013;122(5): 1083-1091.

21. Diedrich JT, Zhao Q, Madden T, et al. Three-year continuation of reversible contraception. Am J Obstet Gynecol2015;213(5):662.e1-8.

22. Birgisson NE, Zhao Q, Secura GM, et al. Preventing unintended pregnancy: the Contraceptive CHOICE Project in review. J Womens Health (Larchmt). 2015;24(5):349-353.

23. McNicholas CP, Madden T, Zhao Q, et al. Cervical lidocaine for IUD insertional pain: a randomized controlled trial. Am J Obstet Gynecol. 2012;207(5):384.e1-6.

24. Clinical Preventive Services for Women: Closing the Gaps. Washington, DC: The National Academies Press; 2011.

25. Stanek AM, Bednarek PH, Nichols MD, et al. Barriers associated with the failure to return for intrauterine device insertion following firsttrimester abortion. Contraception2009;79(3):216-220.

26. Peipert JF, Madden T, Allsworth JE, et al. Continuation and satisfaction of reversible contraception. Obstet Gynecol. 2011;117(5):1105-1113.

27. Madden T, Mullersman JL, Omvig KJ, et al. Structured contraceptive counseling provided by the Contraceptive CHOICE Project. Contraception. 2013;88(2):243-249.

Boosting HPV vaccination rates: A call to action

Faculty

Nancy R. Berman, MSN, ANP-BC, NCMP, FAANP, is a nurse practitioner at Michigan Healthcare Professionals in Farmington Hills and a Clinical Instructor in the Department of Obstetrics and Gynecology at Wayne State University School of Medicine in Detroit, both in Michigan.

Intended audience

This continuing education (CE) activity has been designed to meet the educational needs of nurse practitioners, certified nurse-midwives, and other advanced practice clinicians who care for women.

CE approval period

Now through May 31, 2017

Estimated time to complete this activity

1 hour

CE approval hours

1.0 contact hour of CE credit, including 1.0 contact hour of pharmacology content

Needs assessment

Most cervical cancers are preventable. The incidence of cancer related to HPV infection has declined significantly since the inauguration of screening programs in the U.S. more than 50 years ago. However, too many women are still developing cervical cancer, and 4,400 are dying of it each year. More cases of cervical cancer could be prevented with increased uptake of HPV vaccination, increased addition of HPV testing in screening, and improved access to cervical cancer screening in under-screened and unscreened populations.

Goal statement

Nurse practitioners and other advanced practice clinicians who care for women will make a strong recommendation that children aged 11 or 12 get fully immunized against HPV so as to prevent HPV-related diseases in the future.

Educational objectives

At the conclusion of this educational activity, participants should be able to:

1. Understand the efficacy, safety, and immunogenicity of the HPV vaccine, including the new 9-valent vaccine.

2. Be familiar with all of the ACIP guidelines for the HPV vaccine.

3. Boost HPV vaccine uptake in their patient population.

Accreditation statement

This activity has been evaluated and approved by the Continuing Education Approval Program of the National Association of Nurse Practitioners in Women’s Health (NPWH), and has been approved for 1.0 contact hour of CE credit, including 1.0 contact hour of pharmacology content.

Faculty disclosures

NPWH policy requires all faculty to disclose any affiliation or relationship with a commercial interest that may cause a potential, real, or apparent conflict of interest with the content of a CE program. NPWH does not imply that the affiliation or relationship will affect the content of the CE program. Disclosure provides participants with information that may be important to their evaluation of an activity. Faculty are also asked to identify any unlabeled/unapproved uses of drugs or devices made in their presentation.

Nancy R. Berman, MSN, ANP-BC, NCMP, FAANP, has disclosed that she has financial relationships with Hologic and Shionogi.

Disclosure of unlabeled use

NPWH policy requires authors to disclose to participants when they are presenting information about unlabeled use of a commercial product or device or an investigational use of a drug or device not yet approved for any use.

Disclaimer

Participating faculty members determine the editorial content of the CE activity; this content does not necessarily represent the views of NPWH or Merck & Co., Inc. This content has undergone a blinded peer review process for validation of clinical content. Although every effort has been made to ensure that the information is accurate, clinicians are responsible for evaluating this information in relation to generally accepted standards in their own communities and integrating the information in this activity with that of established recommendations of other authorities, national guidelines, FDA-approved package inserts, and individual patient characteristics.

Successful completion of this activity

Successful completion of this activity, J-16-02, requires participants to:

1. “Sign In” at the top right-hand corner of the website if you have an NPWH account. You must be signed in to receive credit for this course. If you do not remember your username or password, please follow the “Forgot Password” link and instructions on the sign-in page. If you do not have an account, please click on “Create an Account.”

2.Read the learning objectives, disclosures, and disclaimers on the next page.

3.Check “Agree to Terms” on the next page and then click the “Continue” button.

4. Study the material in the learning activity during the approval period (now through May 31, 2017).

5.Complete the posttest and evaluation. You must earn a score of 70% or better on the posttest to receive CE credit.

6.Print out the CE certificate if successfully completed.

Commercial support

This activity is supported by educational grants from Merck & Co., Inc.

Before reading the article, click here to take the pretest.

Cervical cancer, caused in nearly all cases by human papillomavirus (HPV), is considered a vaccinepreventable disease. Anogenital warts and other forms of cancer can also be caused by HPV, and can be reduced in frequency with HPV vaccination. Despite the proven efficacy and safety of the three available HPV vaccines—one of which targets up to nine different HPV genotypes—only about one-third of girls in the United States have received the three recommended doses. The author reviews information about the HPV vaccines and the guidelines for their use, and offers strategies for healthcare providers to implement in order to improve HPV vaccine uptake in their age-appropriate patients.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection in the United States.Almost all sexually active adults are or will be infected by HPV at some point in their lives, even if they have had sex with only one other person. Although the vast majority of HPV infections are asymptomatic and resolve spontaneously, a few persist and can lead to cancer.2 Persistent infections with oncogenic HPV types can cause cancers of the cervix, vulva, vagina, anus, and penis, as well as the oropharynx. Infection with non-oncogenic HPV types can cause anogenital warts.

About 79 million persons in the U.S. are already infected with HPV, and 14 million persons acquire HPV infection each year.3 An estimated 17,600 women and 9,300 men receive a diagnosis of an HPVrelated cancer each year. For U.S. women, cervical cancer is the most common HPV-related cancer; approximately 11,000 women are diagnosed with it annually and 4,400 women die of it. For U.S. men, oropharyngeal cancer is the most common HPV-related cancer; about 7,200 U.S. men are diagnosed with it each year.

In an Annual Report to the Nation on the Status of Cancer, Jemal et alreported that many types of HPV-related cancers were on the rise, some disproportionately affecting certain racial and ethnic minorities. For example, from 2000 to 2009, oral cancer rates increased 4.9% for Native American men, 3.9% for white men, 1.7% for white women, and 1% for Asian men. Anal cancer rates doubled from 1975 to 2009. Vulvar cancer rates rose for white women and African-American women and penile cancer rates increased among Asian men.

Most cervical cancers are preventable. The incidence of this disease has declined significantly since the inauguration of screening programs in the U.S more than 50 years ago.5 However, too many women are still developing cervical cancer, and 4,400 are dying of it each year. More cases of cervical cancer could be prevented with increased uptake of HPV vaccination, increased addition of HPV testing in screening, and improved access to cervical cancer screening in under-screened and unscreened populations.

HPV vaccines

For decades, the best that healthcare providers (HCPs) could offer patients in terms of lowering their risk for developing HPV-related cancers were screenings for cervical cancer precursors and for anal pre-cancers and cancers (in highrisk populations) and inspection for vulvar pre-cancers and cancers. But in June 2006, the FDA approved the first vaccine to prevent disease caused by any of four HPV genotypes: 6 and 11, which cause anogenital warts; and 16 and 18, which are the most common causes of cervical cancer.6

Three HPV vaccines are on the market in the U.S. (Table).The bivalent HPV (2vHPV), quadrivalent HPV (4vHPV) and 9-valent HPV (9vHPV) vaccines each target HPV 16 and 18, the types that cause about 70% of cervical cancers and most other HPV-linked cancers in women and men.3,7 The 9vHPV vaccine targets five additional cancer-causing types (HPV 31, 33, 45, 52, 58), which account for about 15% of cervical cancers. The 4vHPV and 9vHPV vaccines also protect against HPV 6 and 11, the types that cause 90% of anogenital warts.

Efficacy

Clinical trials have suggested that HPV vaccines, if used optimally, could likely prevent most cervical cancers.2 Of 10,000 young women vaccinated as part of clinical trials before they could have been exposed to oncogenic forms of HPV, none developed HPV 16- or 18-associated cervical lesions, which are precursors to invasive cancer.8,9 HPV vaccines have been shown to prevent other HPV 16- or 18-associated anogenital pre-cancers and HPV 6- or 11-associated genital warts with similar efficacy.9,10 Women who received the 2vHPV vaccine as part of a clinical trial had a much lower prevalence of oral HPV infection than did participants who had not received the HPV vaccine.11

In a study reported in March 2016, Markowitz et al12 analyzed 4vHPV type prevalence (i.e., types 6, 11, 16, and 18) in cervicovaginal specimens from females aged 14- 34 years in NHANES (National Health and Nutrition Education Survey) in the pre-vaccine era (2003-2006) and during 4 years of the vaccine era (2009-2012). Within 6 years of HPV vaccine introduction, there was a 64% decrease in 4vHPV type prevalence among females aged 14-19 and a 34% decrease in 4vHPV type prevalence among those aged 20-24 years. There was no decrease in 4vHPV type prevalence in older age groups.

Because the HPV vaccine has been available for only 10 years, it will take a while to assess its efficacy in preventing invasive cancers that take years or decades to develop following persistent infection.

Safety

Three population-based safety studies of the HPV vaccine have been conducted in the U.S.13-15 These studies have identified no serious safety concerns, although one study showed an increased risk of syncope on the day of vaccination and skin infections in the 2 weeks following vaccination.15 Gee et al12 evaluated the risk for venous thromboembolism (VTE) in persons aged 9-26 years, and found no increased risk of VTE following vaccination with the 4vHPV vaccine. Chao et al14 found no association between 4vHPV vaccine use and 16 autoimmune conditions.

According to ongoing safety monitoring by the CDC, most reports of adverse reactions to the vaccine are non-serious.16 Among the 7.6% of reports classified as serious, the most common side effects are headache, nausea, vomiting, and fever. Syncope is a common non-serious problem in both female and male adolescents who receive the HPV vaccine. Of note, syncope is not specific to the HPV vaccine. It is recommended that after receiving the injection, patients remain seated for 15 minutes before leaving the clinical setting.

Impact

Drolet et al17 conducted a systematic review and meta-analysis of 20 studies in 9 high-income countries to assess population-level consequences and herd effects after female HPV vaccination programs  and to verify whether the high efficacy reported in randomized controlled trials was materializing in real-world situations. The investigators found that in countries with female vaccination coverage >50%, HPV type 16/18 infections decreased significantly, by 68%, and anogenital warts decreased significantly, by 61%, between pre- and post-vaccination periods in girls aged 13-19 years. In addition, significant reductions were recorded in HPV types 31, 33, and 45 in this age group of girls, suggesting cross-protection. Furthermore, the incidence of anogenital warts declined significantly in boys younger than 20 years and in women aged 20-39 years, suggesting herd effects. In countries with female vaccination coverage <50%, significant reductions in HPV types 16/18 infection and in anogenital warts occurred in girls younger than 20, with no indication of cross-protection or herd effects.

Duration of immunity

According to a 2011 review, the HPV vaccine was found to provide protection against persistent cervical HPV 16/18 infections for up to 8 years—the maximum time of research follow-up at that point.18 More will be known about the total duration of protection as research continues. To date, no evidence suggests waning immunity such as that seen with the menin go coccal conjugate vaccine, which now requires a second dose. Multiple cohort studies are in progress to monitor the duration of immunity.

More about the 9-valent vaccine

To gain the recent endorsement of the CDC’s Advisory Committee on Immunization Practices (ACIP), the 9vHPV vaccine had to demonstrate efficacy, immunogenicity, and safety.19 In particular, the newest vaccine had to show efficacy in terms of preventing infection and disease related to HPV 31, 33, 45, 52, and 58 in a susceptible population and of generating an antibody response to HPV 6, 11, 16, and 18 that was non-inferior to that generated by the 4vHPV vaccine. Studies conducted by Joura et al20 and Luxembourg et al21 showed precisely that.

In 7 pre-licensure studies, the 9vHPV vaccine was evaluated in more than 15,000 females and males.22 In some studies, the 9vHPV vaccine was compared with the 4vHPV vaccine. The 9vHPV vaccine caused slightly more reactions— primarily swelling and redness—at the injection site. As with the 4vHPV vaccine, side effects associated with the 9vHPV vaccine were generally mild. A video summarizing information about the 9vHPV vaccine is available here.

ACIP guidelines

Routine immunizations for 11- and 12-year-olds include HPV vaccination. HCPs should recommend the HPV vaccine on the same day and in the same way as the other vaccines for preteens.

Age, gender, and vaccine type

ACIP recommends that routine HPV vaccination be initiated at age 11 or 12, although the vaccination series can be started as early as age 9.19 Vaccination is also recommended for females aged 13-26 and for males aged 13-21 who have not been vaccinated previously or who have not completed the 3-dose series. HPV vaccination is recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) who have not been vaccinated previously or have not completed the 3-dose series. Females should receive the 2vHPV, 4vHPV, or 9vHPV vaccine and males should receive the 4vHPV or 9vHPV vaccine. The dosing schedule for each vaccine type is shown in the Table. If the vaccine schedule is interrupted, the vaccination series need not be restarted.

Interchangeability

ACIP recommends that, whenever possible, the HPV vaccination series for females be completed with the same HPV vaccine product.16 If vaccination providers do not know or do not have available the HPV vaccine product previously administered to a given patient, or are in settings transitioning to the 9vHPV vaccine, any available HPV vaccine product may be used to continue or complete the series for females for protection against HPV 16/18, and the 4vHPV or 9vHPV vaccine may be used to continue or complete the series for males.19 There are no data on the efficacy of fewer than 3 doses of 9vHPV.

Concomitant administration with other vaccines

HPV vaccine can be administered at the same visit as other ageappropriate vaccines, such as the tetanus/diphtheria/acellular pertussis (Tdap) and quadrivalent meningococcal conjugate vaccines.16 Giving all indicated vaccines togethe at a single visit increases the likelihood that adolescents will receive each vaccine on schedule. Each vaccine should be administered using a separate syringe at a different anatomic site.

History of sexual abuse or assault

The newest vaccination schedule issued by ACIP recommends that the HPV vaccine be given as early as age 9 or 10 if a child has a history of sexual abuse.23 Studies estimate that 1 in 4 girls and 1 in 20 boys will experience sexual abuse before age 18.

HPV vaccine coverage rates

The HPV vaccine has been available for almost 10 years. Despite its proven efficacy and safety, HPV vaccine coverage rates have been low. In 2012, only 53.8% of 13- to 17- year-old girls had received the first HPV vaccine dose and only 33.4% had completed all 3 recommended doses.24 These rates were substantially lower than HPV vaccine coverage rates in other high-income countries such as Australia and the United Kingdom (71.2% and 60.4%, respectively; Figure).2 More recent reports have indicated some improvement in HPV vaccine coverage rates. For example, in 2014, among girls aged 13-17, 60.0% received at least one dose and 39.7% received the 3 recommended doses.25 The improvement was laudable but insufficient: 6 of every 10 girls in this country are not fully vaccinated against HPV.

Strategies to boost vaccination rates

And, thus, a call to action: Concerted efforts are needed to increase HPV vaccine uptake and achieve its potential to prevent cancers.2 These efforts should promote both initiation of the first dose and completion of all 3 doses for age-eligible adolescents, as well as eligible young adults. What can HCPs do to improve vaccination rates?

1. Keep up to date on what you can do to prevent HPV-related cancers

The CDC launched a new website, HPV: You are the key to cancer prevention, for HCPs so that everything about HPV vaccination is found in one place. The website is easy to navigate; it has only 1 page and 3 tabs: Know the Facts, Commit to the Cause, and Lead the Conversation.26 The recommendations described in items 2, 3, 4, and 6 were also derived from this new CDC website.26

2. Make a strong recommendation

The high coverage rates for the Tdap and meningococcal conjugate vaccines suggest that most preteens and teens are not only going to see their HCP, but they are also getting at least one of the recommended adolescent vaccines.25 However, according to the 2013 National Immunization Survey-Teen, one-third of the parents of girls and more than half of the parents of boys said their child’s HCP had not recommended HPV vaccination—the No. 1 reason for failure to vaccinate their children.27,28 Had the HPV vaccine been administered during visits when another vaccine was given, vaccination coverage for ≥1 dose could have reached 91% by age 13 for adolescent girls born in 2000.25 Evidence shows that an HCP recommendation to get vaccinated is the single most influential factor in determining whether parents gets an immunization for their child!24 HCPs should provide clear and strong recommendations that the HPV vaccine series be given to preteens.

3. Seize the day

Timing is everything.26 Making a strong pitch for preteens to be vaccinated is necessary, but not sufficient. HCPs should take advantage of appropriate opportunities to vaccinate their preteen patients against HPV—for example, during school or camp physical exams—when these patients are still coming in for regular office visits. Once these patients go to college or to work, they are less likely to see their HCP for yearly checkups. To make a timely recommendation, HCPs should do it the same way and the same day that they recommend the Tdap and meningococcal vaccines.

4. Use a reminder system

Reminder systems shown to increase HPV vaccination rates include a reminder letter and direct messaging via automated text, prerecorded voice, and/or postcard.29,30

5. Educate mothers during their routine visits

Another useful strategy is to educate mothers when they are being screened for cervical cancer about the role of HPV infection in cervical cancer. HCPs should explain to mothers that they are undergoing an HPV test to determine whether the virus is present on their cervix, and that their preteen daughters or sons can be vaccinated to be protected from being infected by the HPV types in the vaccine. HCPs can simply say: “HPV is the cause of cervical cancer. We are screening you with the HPV test and the Pap test to detect any existing HPV infection or cervical pre-cancers, which we can then treat to keep them from progressing to cancer. But we can vaccinate your daughters and sons to prevent HPV infection and therefore prevent cervical pre-cancer and cervical cancer.”

6. Address parents’ specific concerns

If a parent’s main concern is side effects, HCPs can say: “Vaccines, like any medication, can have side effects. With the HPV vaccine, the most common side effect is pain and redness at the site of the injection. These symptoms should go away quickly. In addition, the HPV vaccine has not been linked to any serious or long-term side effects.”26 If a parent’s main concern is effect on fertility, HCPs can say, “No scientific data suggest that getting the HPV vaccine has any effect on future fertility. In fact, not getting the HPV vaccine can put a woman’s fertility in jeopardy. Persistent HPV infection can cause cervical cancer, and the treatment of cervical cancer can leave a woman unable to have children. Even treatment for cervical pre-cancer can put a woman at risk for problems with her cervix during pregnancy, causing preterm delivery or other problems.”

7. Hand out written materials

Written materials are helpful in supporting patient education. Patients can refer to them later, after they have spoken to you. Many written materials are available in languages other than English. Spanish-language materials are particularly easy to find. Patient factsheets regarding the HPV vaccine are available on the CDC website.

Conclusion

Considering how effective the HPV vaccine will be in preventing cervical cancer, as well as other HPV-related cancers in both females and males, virtually all preteen girls and boys and all eligible young women and men should be immunized. Vaccination uptake rates, although increasing slowly, are still much too low. These rates will rise dramatically only when HCPs across the country heed the call to action and educate parents about the efficacy and safety of this vaccine and take advantage of opportunities to initiate and complete administration of the 3-dose series.

References

1. Centers for Disease Control and Prevention (CDC). Genital HPV Infection – Fact Sheet. Last updated February 3, 2016.

2. President’s Cancer Panel Annual Report 2012-2013. Accelerating HPV Vaccine Uptake: Urgency for Action to Prevent Cancer.

3. CDC. Clinician Factsheets. HPV Vaccination Information for Clinicians. Page last updated December 29, 2015.

4. Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013; 105(3):175-201.

5. National Cancer Institute. A Snapshot of Cervical Cancer: Incidence and Mortality. November 5, 2014.

6. FDA. June 8, 2006 Approval Letter — Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant.

7. CDC. Clinician Factsheets. Supplemental Information and Guidance for Vaccination Providers Regarding Use of 9- Valent HPV Vaccine. Page last updated December 29, 2015.

8. Lehtinen M, Paavonen J, Wheeler CM, et al. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-ofstudy analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13(1):89-99.

9. Muñoz N, Kjaer SK, Sigurdsson K, et al. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPVassociated genital diseases in young women. J Natl Cancer Inst. 2010;102(5):325-339.

10. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011; 365(17):1576-1585.

11. Herrero R, Quint W, Hildesheim A, et al. Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLoS One. 2013;8(7):e68329.

12. Markowitz LE, Liu G, Hariri S, et al. Prevalence of HPV after introduction of the vaccination program in the United States. Pediatrics. 2016;137(3):1-9.

13. Gee J, Naleway A, Shui I, et al. Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink. Vaccine. 2011;29(46):8279-8284.

14. Chao C, Klein NP, Velicer CM, et al. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med. 2012;271(2):193-203.

15. Klein NP, Hansen J, Chao C, et al. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Arch Pediatr Adolesc Med. 2012;166(12):1140-1148.

16. Markowitz LE, Dunne EF, Saraiya M, et al; CDC. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP)MMWR. 2014;63(RR-05):1-30.

17. Drolet M, Bénard É, Boily MC, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and metaanalysis. Lancet Infect Dis. 2015;15(5):565-580.

18. Romanowski B. Long term protection against cervical infection with the human papillomavirus: review of currently available vaccines. Hum Vaccine. 2011;7(2):161-169.

19. Petrosky E, Bocchini JA Jr, Hariri S, et al; CDC. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices. MMWR. 2015;64(11):300-304.

20. Joura EA, Giuliano AR, Iversen OE, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711-723.

21. Luxembourg A, Bautista O, Moell er E, et al. Design of a large outcome trial for a multivalent human papillomavirus L1 virus-like particle vaccine. Contemp Clin Trials. 2015;42:18-25.

22. Markowitz L. CDC Expert Commentary. Common Questions About 9-Valent HPV Vaccine. Medscape Pharmacists. June 22, 2015.

23. Advisory Committee on Immunization Practices (ACIP). Recommended Immunization Schedules for Persons Aged 0 Through 18 Years. United States. 2016.

24. CDC. Human papillomavirus vaccination coverage among adolescent girls, 2007-2012, and postlicensure vaccine safety monitoring, 2006-2013—United States. MMWR. 2013; 62(29):591-595.

25. CDC. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2014. MMWR. 2015;64(29):784- 792.26. CDC.

26. Human Papillomavirus (HPV). For Clinicians. HPV: You Are the Key to Cancer Prevention. Page last updated September 30, 2015.

27. CDC. Human Papillomavirus Vaccination Coverage Among Adolescents, 2007–2013, and Postlicensure Vaccine Safety Monitoring, 2006–2014 — United States. MMWR. 2014;63(29):620-624.

28. Newitt VN. HPV vaccination: Are you doing enough to make sure that your patients are protected? Nurse Pract Perspect. 2015;2(4):32-36.

29. Chao C, Preciado M, Slezak J, Xu L. A randomized intervention of reminder letter for human papillomavirus vaccine series completion. J Adolesc Health. 2015;56(1):85-90.

30. Bar-Shain DS, Stager MM, Runkie AP, et al. Direct messaging to parents/guardians to improve adolescent immunizations. J Adolesc Health. 2015;56(5 suppl):S21-S26.

The cervical cancer screening dilemma: Choosing the optimal screening strategy

Faculty

Kim Choma, DNP, APN, WHNP-BC, is a Part-time Lecturer at Rutgers University School of Nursing in Camden, New Jersey.

Charles F. Dubin, MD, is a Assistant Clinical Professor at the UCLA David Geffen School of Medicine, University of California at Los Angeles in Los Angeles, California.

Intended audience

This continuing education (CE) activity has been designed to meet the educational needs of women’s health nurse practitioners (NPs), adult NPs, family NPs, and certified nurse midwives (CNMs) involved in women’s health.

CE approval period

Now through March 31, 2017

Estimated time to complete this activity

1 hour

CE approval hours

1.0 contact hour of CE credit

Needs assessment

The essence of the cervical cancer screening (CCS) dilemma is which screening test(s) to use and how frequently to screen. Major national health organizations may differ somewhat in terms of their specific recommendations, but their

general objectives are to prevent morbidity and mortality from cervical cancer (Saslow et al, 2012 [this article presents recommendations from the American Cancer Society, the American Society of Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology]; U.S. Preventive Services Task Force, 2012; American College of Obstetrics and Gynecology, 2012) and to prevent overzealous management of precursor lesions that most likely will regress or disappear.

Educational objectives

At the conclusion of this educational activity, participants should be able to:

1.Understand the importance of maximizing the benefits of cervical cancer prevention while minimizing the harms associated with overtreatment.

2. Evaluate current available options for CCS: cervical cytology, primary HPV testing, and co-testing.

3.Determine the optimal interval for CCS for each patient.

Accreditation statement

This activity has been evaluated and approved by the Continuing Education Approval Program of the National Association of Nurse Practitioners in Women’s Health (NPWH), and has been approved for 1.0 contact hour of CE credit.

Faculty disclosures

NPWH policy requires all faculty to disclose any affiliation or relationship with a commercial interest that may cause a potential, real, or apparent conflict of interest with the content of a CE program. NPWH does not imply that the affiliation or relationship will affect the content of the CE program. Disclosure provides participants with information that may be important to their evaluation of an activity. Faculty are also asked to identify any unlabeled/unapproved uses of drugs or devices made in their presentation.

Kim Choma, DNP, APN, WHNP-BC, has disclosed that she serves on the Speakers’ Bureau and advisory board of Hologic.

Charles Dubin, MD, reports that he serves on the Speakers’ Bureau of Hologic, Myriad Genetics, and Phenogen Sciences.

Disclosure of unlabeled use

NPWH policy requires authors to disclose to participants when they are presenting information about unlabeled use of a commercial product or device or an investigational use of a drug or device not yet approved for any use.

Disclaimer

Participating faculty members determine the editorial content of the CE activity; this content does not necessarily represent the views of NPWH or Hologic. This content has undergone a blinded peer review process for validation of clinical content. Although every effort has been made to ensure that the information is accurate, clinicians are responsible for evaluating this information in relation to generally accepted standards in their own communities and integrating the information in this activity with that of established recommendations of other authorities, national guidelines, FDA-approved package inserts, and individual patient characteristics.

Successful completion of this activity

Successful completion of this activity, J-16-01, requires participants to:

1. “Sign In” at the top right-hand corner of the page (npwh.org/courses/home/details/559) if you have an NPWH account. You must be signed in to receive credit for this course. If you do not remember your username or password, please follow the “Forgot Password” link and instructions on the sign-in page. If you do not have an account, please click on “Create an Account.”

2.Read the learning objectives, disclosures, and disclaimers on the next page.

3.Check “Agree to Terms” on the next page and then click the “Continue” button.

4. Study the material in the learning activity during the approval period (now through March 31, 2017).

5.Complete the posttest and evaluation. You must earn a score of 70% or better on the posttest to receive CE credit.

6.Print out the CE certificate if successfully completed.

Commercial support: This activity is supported by educational grants from Hologic.

Before reading the article, click here to take the pretest.

The authors evaluate current available options for cervical cancer screening (CCS), with an emphasis on the importance of maximizing the benefits of cancer prevention while minimizing the harms associated with overtreatment. Two major dilemmas are addressed: Which CCS method is recommended for women aged 30-65? and What is the optimal interval between screenings for women in any age group?

Cervical cancer screening (CCS) has been one of the most successful screening programs in United States history, reducing cervical cancer-related incidence and mortality by 45% and 49%, respectively, since 1980.1 Until fairly recently, yearly cytology testing was recommended to maximize detection of pre-cancerous lesions. The discovery that infection with the human papillomavirus (HPV) underlies the pathophysiology of nearly all cervical cancers led to the incorporation of HPV testing in general screenings of women aged 30 years or older, starting in 2003.2, 3

Unlike few other forms of cancer, cervical cancer is nearly always

preventable.4 Under optimal circumstances, each potential case of cervical cancer can be forestalled by identifying and treating

disease that progresses, at most, to the high-grade cancer precursor stage.5, 6 At the same time, healthcare professionals (HCPs) want to minimize the harms associated with overtreatment of benign

lesions not destined to become cancerous.6

The cervical cancer screening dilemma

The essence of the CCS dilemma is which screening test(s) to use and how frequently to screen. Major national health organizations may differ somewhat in their specific recommendations, but their general objectives are to prevent morbidity and mortality from cervical cancer and to prevent overzealous management of precursor lesions that most likely will regress or disappear.6, 7

Which cervical cancer screening tests are available?

Two tests, cervical cytology and the HPV test, are used to screen for cervical cancer. In essence, though, HCPs have three CCS options: cytology alone, the HPV test alone (known as the primary HPV test), and co-testing with both methods.

Cervical cytology

A sample of cervical cells is examined under a microscope to screen for premalignant cells that could signal the presence of cancer precursors.8 Cervical cells collected by an HCP are smeared on a glass slide (traditional or conventional cytology—that is, the Pap test) or added to a preservative fluid (liquid-based thin-layer test). Liquid-based cytology, because of its greater sensitivity than conventional cytology in detecting disease, enables extension of the screening interval from 1 year to up to 3 years—without significantly diminishing CCS effectiveness.9

HPV testing

The causal role of persistent HPV infection in the development of cervical cancer and its precursors has been well documented.10 A landmark 2010 study showed that, over a 60-year study period, the 8 most common HPV types identified were (in descending order of frequency) 16, 18, 45, 33, 31, 52, 58, and 35.11 Together, these genotypes account for 91% of all cases of cervical cancer. HPV 16, 18, and 45 were found in 75% of the most common type of cervical cancer (squamous cell) and in 94% of the second most common form (adenocarcinoma). A study of more than 20,000 women showed that those infected with HPV types 16 and/or 18, versus those infected with other high-risk types, had a 10 times greater risk of developing cervical cancer.12 Because HPV cannot be cultured, in most cases its accurate identification relies on molecular biology techniques.13 Molecular assays use primers and probes that identify a region of HPV DNA or HPV mRNA. Of note, HPV tests used in clinical practice need to be FDA approved for validity.6

Co-testing

Recent incorporation of HPV DNA testing into CCS strategies offers the benefits of increasing early disease detection (up to 100% sensitivity) 14 and increasing the length of the interval between screenings—thereby lessening harms such as the adverse psychosocial impact of screening positive, the need for additional visits and procedures, and the treatment of lesions that would have resolved on their own.6 Even more recently, HPV infection can be identified by HPV mRNA testing, which, like standard HPV DNA testing, has up to 100% sensitivity15 but also offers improved specificity, with a 24% reduction in false-positive results.16

Which approaches to screening are recommended for women aged 21-29?

According to guidelines issued in 2012 by the American Cancer Society (ACS), the American Society of Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP), CCS should begin at age 21.6 Women aged 21-29 should undergo cervical cytology every 3 years.6 The same year, the U.S. Preventive Services Task Force (USPSTF) and the American Congress of Obstetricians and Gynecologists (ACOG) issued similar recommendations.17, 18 These organizations all advised against HPV co-testing in women younger than 30; although HPV is commonly present in women in this age group, most of them successfully fight off the infection within a few years.19 An updated Practice Bulletin from ACOG published in January 2016 reinforces the recommendations for women aged 21-29 based on level A evidence: Co-testing in these women and annual cytology should not be performed.20 Until more longterm, level A evidence studies are available to support future updates to the 21-29 age group, HCPs are encouraged to follow the consensus guidelines.6 Although primary HPV testing was not recommended at the time of the ACS/ASCCP/ASCP, USPSTF, and ACOG updates in 2012—in fact, its use was specifically discouraged in women in their 20s—the body of evidence supporting this CCS approach has grown. Findings from the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study (2008-2012) supported the safety and effectiveness of primary HPV testing.21, 22 In 2014, the FDA approved the use of the cobas HPV test as a primary screen for cervical cancer in women aged 25 years or older.23 As a result, interim clinical guidance issued by the Society of Gynecologic Oncology (SGO) and the ASCCP in 2015 supported primary HPV testing as a possible alternative to cytology-based screening and co-testing, but starting no sooner than age 25.24

Which approaches to screening are recommended for women aged 30-65?

Again, HCPs have three CCS options: cervical cytology, primary HPV testing, and co-testing. The ACS/ASCCP/ASCP recommends cytology alone every 3 years or cotesting every 5 years.6 The USPSTF endorses cytology every 3 years, with co-testing as an option in women who want to extend their screening interval to 5 years.17 ACOG supports the options of cytology at 3-year intervals and co-testing at 5-year intervals, with the latter preferred.18 None of these organizations advocates the use of primary HPV testing as an alternative to cytology or co-testing.

Co-testing for women aged 30 or older was approved by the FDA in 2006. But how does co-testing compare with primary HPV testing— as advocated in the interim guidance report—and with cervical cytology alone in predicting outcomes in women in the 30- to 65-year age group?

Studies supporting co-testing 

Blatt et al25 conducted a retrospective study to assess the sensitivity of various testing options for biopsy-proven cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The authors evaluated 256,648 cervical biopsies from women aged 30-65 who had undergone a co-test and colposcopy within 1 year of each other (colposcopy was performed a mean of 54 days after the co-testing result). Among the samples, 4,090 (1.6%) exhibited CIN3+. A positive co-test result was 98.8% sensitive for diagnosing CIN3+, compared with the 94% sensitivity of a positive HPV test result and the 91.3% sensitivity of a positive cytology result. Looked at another way, in this group of women, use of cytology alone would have missed 8.7% of the CIN3+ cases and use of the HPV test alone would have failed to catch 6% of the CIN3+ cases, whereas co-testing would have missed only 1.2% of these cases. Therefore, co-testing identified 80% of the CIN3+ cases that would have been missed by screening with the primary HPV test. Of the 526 confirmed cases of cervical cancer in this study, 98 (18.6%) were HPV test negative and 64 (12.2%) were cytology negative, whereas only 29 (5.5%) were cotest negative. Co-testing identified 70% of cervical cancers that would have been missed by screening with the HPV test alone.

Additional studies conducted over the past 11 years showed that primary HPV testing missed a substantial proportion of cervical cancers, and were in concordance with the landmark study by Blatt and colleagues.11, 26-29

Studies supporting primary HPV testing

The aforementioned interim guidance from the SGO/ASCCP was based, in large part, on the results of several large trials demonstrating that a negative HPV test result provides greater reassurance of low CIN3+ risk than does a negative cytology result. For example, Dillner et al30 evaluated primary data from seven HPV screening studies in six European Union countries, each investigating the predictive value of primary HPV testing for future CIN3+. The cumulative incidence rate of CIN3+ after 6 years was considerably lower among women negative for HPV at baseline (0.27%) than among women with negative results on cytology (0.97%). The cumulative incidence rate among women who were cytology-negative/HPV-positive rose continuously over time, reaching 10% at 6 years, whereas the rate among women who were cytologypositive/HPV-negative remained below 3%.

Other recent studies provided evidence that a negative HPV test result, as compared with a negative cytology result, offers greater reassurance that a woman will be free of CIN3+ over time.31-33 In these studies, participants underwent co-testing. In essence, the investigators found that the HPV test results, relative to the cytology results, were more predictive of outcomes over 3-5 years. That is, the cytology portion of the cotest did not add much information to the HPV portion, suggesting, to some at least, that HPV testing could be used by itself.

The first dilemma: Which CCS method is recommended for women aged 30-65?

The findings of the studies supporting primary HPV testing are open to interpretation. For example, Gage et al32 compared the risks of CIN3+ and of cervical cancer alone for HPV testing every 3 years, cytology testing every 3 years, and co-testing every 5 years among more than 1 million women in the Kaiser Permanente population who were aged 30-64 years and who tested HPV-negative and/or cytology-negative in routine screening. Investigators found that 3-year risks following an HPV-negative result were lower than 3-year risks following a cytology-negative result (CIN3+, 0.069% vs. 0.19%; P <.0001; cancer, 0.011% vs. 0.020%; P<.0001) and 5-year risks following an HPV-negative/Pap-negative co-test result (CIN3+, 0.069% vs. 0.11%; P <.0001; cancer, 0.011% vs. 0.014%; P = .21). That is, the 3- year safety (i.e., reassurance against future risk of pre-cancer and cancer) conferred by a negative HPV test result exceeded the 3-year safety conferred by a negative cytology result or the 5-year safety conferred by a negative cotest result. However, a closer look at the data shows that if HPV testing had been compared with cotesting at the 3-year checkpoint instead of the 5-year checkpoint (the recommended interval), negative co-testing results at baseline were slightly more reassuring than negative HPV results at baseline for CIN3+ and for cancer.

In addition, as HPV-infected cervical cells progress toward cervical cancer, HPV DNA levels decline.34 Depending on the age at which CCS begins and the frequency with which it is performed, relying initially, solely, or mainly on the results of HPV DNA screening tests might miss fastgrowing cancers. Although as HPV integrates itself into the human genome and HPV DNA levels decrease, HPV E6/E7 mRNA levels increase, suggesting that the assay that particularly targets this protein, as compared with the HPV DNA assays, is more specific in indicating lesion severity.35 

Furthermore, with cytology alone, adenocarcinoma and its precursors are difficult to identify— simply because of the cervical anatomy and the detection methods used. Cervical adenocarcinoma is usually farther away from the transformation zone, the area targeted most readily with the use of cervical sampling devices. Cytology alone has been relatively ineffective in identifying glandular lesions associated with adenocarcinoma. Addition of HPV testing to cytology—that is, co-testing—should enhance identification of adenocarcinoma and its precursor, adenocarcinoma in situ (ACIS).18

At this point in time, co-testing seems a reasonable option in women aged 30-65 years because it offers optimal sensitivity and specificity in identifying cervical cancer precursors.

What is the optimal screening interval for cervical cancer screening?

The 2012 ACS/ASCCP/ASCP and ACOG guidelines’ recommended screening intervals are 3 years for liquid-based cytology testing and 5 years for co-testing.6, 18 The updated Practice Bulletin from ACOG states that co-testing every 5 years is preferred, but that screening with cytology alone every 3 years is acceptable.20 ACOG recommends against annual testing. The USPSTF recommends cytology every 3 years for women younger than 30.17 For women aged 30-65 who want to extend their screening interval to 5 years, adding HPV testing is advised. The interim guidance provided by the SGO/ASCCP recommends that re-screening after a negative primary HPV test result occur no sooner than every 3 years—but only in women aged 25 years or older.24

For decades in the past, women underwent conventional Pap testing every year—their single best option for identifying cervical cancer precursors in a timely fashion. But there was a distinct downside to this yearly testing, which often yielded results—atypical squamous cells of undetermined significance (ASCUS) or a higher-grade lesion—that would lead to colposcopy and, depending on the results of the cervical biopsies, a loop electrosurgical excision procedure or conization. Most of these cytologic abnormalities, as well as the HPV infections underlying them, resolve on their own. Screening women every year, then, is bound to lead to unnecessary diagnostic and therapeutic procedures. These procedures are, at the very least, unpleasant and worrisome and at worst, harmful.36-41

The second dilemma: What is the optimal interval between screenings for women in any age group? 

Since the CCS guidelines were published in 2012 and the interim guidance was published last year, a different perspective on the CCS interval has been offered. According to a commentary by Kinney et al,42 which was based on a modeling study for the USPSTF that was published in 2013,43 women who comply with the CCS recommendations and increase the co-testing interval from 3 years to 5 years are increasing their risk for unfavorable consequences, with an additional 1/369 diagnosed with cancer in her lifetime and 1/1,639 dying of cancer. Adoption of a 3-year co-testing interval instead of a 5-year co-testing interval between screenings would “cost” 409 additional colposcopies and 14.3 additional women treated for each cancer death prevented. Many women and their HCPs might argue that the extra screenings, tests, treatments, and related harms are worth it to save even a small number of lives. In  addition, as noted in the discussion of the first CCS dilemma, results of the study by Gage et al32 suggest that the optimal interval for co-testing may be 3 years, not 5 years. Finally, there is considerable clinician resistance to the 5-year screening interval recommended for a negative co-test result.42

Based on what is known to date, HCPs should consider the optimal CCS screening interval to be 3 years, both for cytologic testing in women aged 21-29 or older and for co-testing in women aged 30-65. 

At what age can cervical cancer screening safely be stopped?

According to the ACS/ASCCP/ASCP, CCS can safely be stopped in women older than 65 who have had adequate negative prior screening (three consecutive negative cytology results or two negative co-test results within the previous 10 years, with the most recent test performed within the past 5 years) and no history of CIN2+ within the past 20 years.6 The USPSTF and ACOG are in general agreement with these criteria.17, 18 For women older than 65 with a history of CIN2, CIN3, or ACIS, routine screening should continue for at least 20 years.6, 18 According to the USPSTF, women older than 65 who have never been screened, women who do not meet the criteria for adequate prior screening, or women for whom the adequacy of prior screening cannot be accurately accessed or documented should undergo routine CCS.17 Likewise, routine screening should continue for at least 20 years after spontaneous regression or appropriate management of a highgrade pre-cancerous lesion, even if this extends screening past age 65.

Conclusion

The best approach to prevent cervical cancer entails screening and vaccination. The goals of maximizing benefits and minimizing harms for patients are guiding principles at the forefront of CCS. To this end, using the evidence to date, which includes the 2012 guidelines, the interim guidance published last year, and the updated ACOG practice bulletin, cytology screening every 3 years in women aged 21-29 and co-testing every 3 years in women aged 30-65 are reasonable recommendations to balance patient harms and clinician resistance to 5- year screening intervals.

References

1. National Cancer Institute. A Snapshot of Cervical Cancer: Incidence and Mortality. November 5, 2014.

2. FDA Patient Safety News: Show #16, June 2003.

3. National Cancer Institute. HPV Testing to Screen for Cervical Cancer.

4. Centers for Disease Control and Prevention. CDC Vital Signs. Cervical cancer is preventable. November 2014.

5. Cox JT, Castle PE, Behrens CM, et al; Athena HPV Study Group. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from

the ATHENA HPV study. Am J Obstet Gynecol. 2013;208(3):184.e1-184.e11.

6. Saslow D, Solomon D, Lawson HW, et al; ACS-ASCCP-ASCP Cervical Cancer Guideline Committee. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. J Low Genit Tract Dis. 2012;16(3):175-204.

7. American Society for Colposcopy and Cervical Pathology (ASCCP). Cervical Cancer Screening Recommendations. PowerPoint Presentation. 2012.

8. Kelsey B. The role of HPV testing: co-test or primary screen? Womens Healthcare. 2015;3(2):29-32.

9. Gibb RK, Martens MG. The impact of liquid-based cytology in decreasing the incidence of cervical cancer. Rev Obstet Gynecol. 2011;4(suppl 1):S2-S11.

10. Bosch FX, Lorincz A, Muñoz N, et al. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55(4):244-265.

11. de Sanjose, S, Quint WG, Alemany L, et al; Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048-1056.

12. Khan MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005; 97(14):1072-1079.

13. Abreu ALP, Souza RP, Gimenes F, Consolaro MEL. A review of methods for detect human Papillomavirus. Virol J. 2012;9:262.

14. HC2 High-Risk HPV DNA Test® Package Insert (B). Kaiser Study Data. Test Performance Versus Consensus Histology Results (CIN2-3+) Ages <30.

15. Arbyn M, Roelens J, Cuschieri K, et al. The APTIMA HPV assay versus the Hybrid Capture 2 test in triage of women with ASC-US or LSIL cervical cytology: a meta-analysis of the diagnostic accuracy. Int J Cancer. 2013; 132(1):101-108.

16. Aptima® HPV Assay Package Insert.

17. United States Preventive Services Task Force. Screening for Cervical Cancer. 2012.

18. Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin Number 131: screening for cervical cancer. Obstet Gynecol. 2012;120(5):1222-1238.

19. Bosch FX, Broker TR, Forman D, et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013;31(31 suppl 7):H1-H31.

20. American Congress of Obstetricians and Gynecologists. Practice Bulletin Number 157. Cervical Cancer Screening and Prevention. Obstet Gynecol. 2016;127(1):185-187.

21. Cox JT, Castle P, Behrens C, et al. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol. 2013;208(3): 184.e1-c11.

22. Wright TC, Stoler M, Behrens C, et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015; 136(2):189-197.

23. U.S. Food and Drug Administration. FDA approves first human papillomavirus test for primary cervical cancer screening. FDA News Release April 24, 2014.

24. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol. 2015; 125(2):330-337.

25. Blatt AJ, Kennedy R, Luff RD, et al. Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices. Cancer Cytopathol. 2015;123(5):282-288.

26. de Cremoux P, Coste J, Sastre-Garau X, et al; French Society of Clinical Cytology Study Group. Efficiency of the hybrid capture 2 HPV DNA test in cervical cancer screening. A study by the French Society of Clinical Cytology. Am J Clin Pathol. 2003; 120(4):492-499.

27. Naucler P, Ryd W, Tørnberg S, et al. Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening. J Natl Cancer Inst. 2009;101(2):88-99.

28. Li Z, Austin RM, Guo M, Zhao C. Screening test results associated with cancer diagnoses in 287 women with cervical squamous cell carcinoma. Arch Pathol Lab Med. 2012;136(12): 1533-1540.

29. Zhao C, Li Z, Austin RM. Cervical screening test results associated with 265 histopathologic diagnoses of cervical glandular neoplasia. Am J Clin Pathol. 2013;140(1):47-54.

30. Dillner J, Rebolj M, Birembaut P, et al; Joint European Cohort Study. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ. 2008;337:a1754.

31. Katki HA, Kinney WK, Fetterman B, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncol. 2011;12(7):663-672.

32. Gage JC, Schiffman M, Katki HA, et al. Reassurance against future risk of precancer and cancer conferred by a negative human papillomavirus test. J Natl Cancer Inst. 2014;106(8).

33. Ronco G, Dillner J, Elfström, EM, et al; International HPV screening working group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):524-532.

34. Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond). 2006;110(5):525-541.

35. Lie AK, Kristensen G. Human pap illomavirus E6/E7 mRNA testing as a predictive marker for cervical carcinoma. Expert Rev Mol Diagn. 2008; 8(4):405-415.

36. Sawaya G, Kuppermann M. Identifying a “range of reasonable options” for cervical cancer screening. Obstet Gynecol. 2015;125(2):308-310.

37. Sharp L, Cotton S, Cruickshank M, et al; TOMBOLA Group. The unintended consequences of cervical screening: distress in women undergoing cytologic surveillance. J Low Genit Tract Dis. 2014;18(2):142-150.

38. Sutthichon P, Kietpeerakool C. Perioperative complications of an outpatient loop electrosurgical excision procedure: a review of 857 consecutive cases. Asian Pac J Cancer Prev. 2009;10(3):351-354.

39. Kyrgiou M, Koliopoulos G, Martin- Hirsch P, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and metaanalysis. Lancet. 2006;367(9509): 489-498.

40. Ørtoft G, Henriksen TB, Hansen ES, Petersen LK. Preterm birth and previous conisation of the cervix. Br J Obstet Gynaecol. 2010;117(9):1158-1169.

41. Arbyn M, Kyrgiou M, Simoens C, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ. 2008;337:a1284.

42. Kinney W, Wright TC, Dinkelspiel HE, et al. Increased cervical cancer risk associated with screening at longer intervals. Obstet Gynecol. 2015; 125(2):311-315.

43. Kulasingam SL, Havrilesky LJ, Ghebre R, Myers ER. Screening for cervical cancer: a modeling study for the US Preventive Services Task Force. J Low Genit Tract Dis. 2013; 17(2):193-202.

Overactive bladder: Assessing patient goals and implementing individualized treatment

 

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Overactive bladder (OAB) is a common condition affecting women in every age bracket. OAB symptoms need no longer undermine a woman’s quality of life. After ascertaining a patient’s goals, a healthcare provider can devise an individualized treatment plan that may include simple lifestyle changes, an FDA-approved medication regimen, and nonpharmacologic interventions such as pelvic floor muscle exercises, bladder training, and use of a pessary.

Key words: overactive bladder, OAB, urinary incontinence, nocturia, anticholinergics, beta-3 adrenergic agonist

Anita Padd, age 69, is a retired registered nurse who presents with a list of urinary complaints that she attributes to the fact that, when she was working, she was too busy to take time to go to the bathroom. A week before her appointment, Anita had attended a luncheon sponsored by a nurse practitioner (NP) who recently opened a pelvic health center around the corner. Anita says that she is glad both that she attended the luncheon—“For the first time in years, I realized that I am not alone and that help is available for my bladder problems”—and that she has made an appointment to see this NP.

Why are so many women experiencing bladder problems now?

Anita, born in 1946, was among the first Baby Boomers to turn 65. She, like many of her peers, is healthier than members of previous generations and has lived long enough to develop one or more chronic health conditions such as hypertension, diabetes, and overactive bladder (OAB). According to the U.S. Census Bureau, in 2014 there were 76.4 million Baby Boomers—that is, persons born between 1946 and 1964.1 The number and proportion of elderly persons in the country will keep rising for many years to come.
Anita believes that her bladder problem is a normal consequence of aging. She has been managing the problem by restricting her fluid intake and wearing pads. She tells the NP that she didn’t broach the topic to her primary care provider (PCP) because she was embarrassed and because she feared that surgery was the only treatment available.

Are Anita’s perceptions/concerns about her bladder problem common?

Results of a 2012 nationwide survey of women aged 40-65 years showed that those who had mild to moderate OAB symptoms (n = 652), as compared with those who had no OAB symptoms (n = 1,017), tended to feel much less “in charge” of their lives and their health and were much more fearful of public embarrassment related to not being able to reach a toilet in time to avoid having an accident.2 OAB sufferers were also more likely to think that bladder problems, like wrinkles and gray hair, were a normal part of aging.

Anita’s PCP has never screened her for urinary problems. Like many PCPs, she manages hundreds of patients with multiple conditions and feels that investigating a condition such as OAB would be “opening Pandora’s box.” Like her patient, this PCP is not aware of conservative treatments for bladder problems and is confused by all the medications on the market.

How common is OAB? Should healthcare providers (HCPs) be routinely screening their patients for it?

The prevalence of OAB among women is 15%-17%.3,4 In raw numbers, at least 11-16 million women in the United States have OAB symptoms.4 Most women with OAB symptoms do not talk with their HCPs about their urinary dysfunction, and providers may not routinely inquire about it. As a result, only a small minority of women with OAB receive treatment for it.4
Healthcare providers who see women on a regular basis in their practice can fill the gap by routinely screening for OAB and by gaining the knowledge to treat it appropriately. In an NPWH member survey of 300 NPs that was conducted in 2013, 48.3% of respondents reported being confident in their ability to diagnose OAB and 41.1% felt sure of themselves with regard to treating OAB, but only 28.5% thought that most OAB sufferers in their practice had been identified (H.A.C., unpublished NPWH member survey data, 2013). With proper screening for OAB, most, if not all, of the patients with this condition can be identified and treated.

What exactly is overactive bladder?

Overactive bladder is a symptom complex consisting of urgency, frequency, and nocturia and, in 37% of cases, urge incontinence. Sudden and compelling urinary urgency, the hallmark of OAB, occurs as a result of premature and independent contractions of the bladder that escape inhibition by the central nervous system. Urinary frequency is defined as voiding 8 or more times in a 24-hour period.5 Nocturia entails awakening more than 2 times a night to urinate.5 For OAB sufferers who have urge incontinence, urine loss varies from a few drops to a “gush.”

The three main categories of urinary incontinence are urge incontinence, stress incontinence, and mixed incontinence. Urge incontinence is an involuntary loss of urine immediately preceded by or synchronous with a strong urge to void. Urine loss can be substantial, because bladder contractions may continue until the bladder is empty. Urge incontinence, also described as detrusor instability or detrusor hyperactivity,6 differs from a normal strong urge to void that can be controlled. It is due to spontaneous bladder spasm, which can result from dietary factors (bladder stimulants such as caffeine or alcohol), increased fluid intake, side effects of medication (e.g., diuretics, bethanechol), urinary tract infection/cancer, or nerve dysfunction associated with nerve trauma, diabetes, multiple sclerosis, or spinal cord injury.5,6 Many episodes of urge incontinence have triggers such as unlocking the door to one’s house upon return (key-in-lock syndrome), approaching a toilet, or hearing the sound of running water.7Stress incontinence is marked by an involuntary loss of urine due to increased abdominal pressure on the bladder that exceeds maximal urethral closure pressure.8 An episode of stress incontinence is precipitated by an activity such as coughing, sneezing, laughing, lifting, stepping off a curb, or tripping. Stress incontinence is due to an increase in abdominal forces in the presence of an anatomic weakness of the bladder neck, which typically maintains the seal of urine during activity. It can stem from a variety of situations (e.g., coughing) or conditions such as vaginal delivery, aging, estrogen deficiency associated with meno­pause, or obesity.6 Stress incontinence differs from urge incontinence in that it (1) is rarely associated with nocturia or an urge to urinate; (2) is precipitated by an activity such as coughing; and (3) often occurs at unexpected or inappropriate times.

Mixed incontinence is a combination of stress incontinence and urge incontinence. It is described as stress dominant or urge dominant. Its occurrence increases with aging.

Anita sits on the examination table at the NP’s office. Her complaints include (1) severe urgency to urinate when she arrives at home; (2) urinary frequency in the late morning; (3) nocturia: she needs to urinate 3-4 times a night, although she is thankful that she can usually go back to sleep; (4) urine leaking with position change when her bladder is full; and (5) feeling exhausted all the time. Anita indicates that she took hormone therapy years ago, but not recently. She reports vaginal dryness and long-standing constipation. She also reports that she takes cranberry pills because they are “good for the bladder.”

What does the workup for a patient with suspected OAB entail?

In its most recent guideline. the American Urological Association (AUA) lists these clinical diagnostic principles:

  • Minimum requirements are a careful history, physical examination, and urinalysis.
  • If deemed necessary, a urine culture and/or post-void residual assessment may be performed and information from bladder diaries and/or symptom questionnaires may be obtained.
  • Urodynamics, cystoscopy, and diagnostic renal and bladder ultrasound are not needed in the initial workup of a patient with an uncomplicated pre­sentation.9

History

The history includes a general health history and a focused history regarding lower urinary tract symptoms, including their onset, nature, duration, severity, and effect on quality of life.5 The HCP inquires about the presence or absence of diabetes, neurologic disorders, recurrent urinary tract infection, hematuria, kidney stones, previous lower abdominal or pelvic surgery, pelvic organ prolapse (POP), and vaginitis.10 In addition, the HCP asks the patient about her use of prescription and over-the-counter medications, particularly with regard to anticholinergics or antimuscarinics, antidepressants, antipsychotics, sedatives or hypnotics, diuretics, caffeine, alcohol, opioids, alpha-adrenergic blockers, alpha-adrenergic agonists, beta-adrenergic agonists, and calcium channel blockers.5 The HCP then poses screening questions specific to OAB:

  • Do you ever leak urine when you have a strong urge on the way to the bathroom? How often?
  • How frequently do you urinate during the day?
  • How many times do you get up to urinate after going to sleep? Is it the urge to urinate that wakes you?
  • How many pads a day do you wear for protection?
  • Does this problem inhibit any activity or prevent you from doing things you like to do?

Physical examination

A comprehensive physical examination for OAB includes a pulmonary and cardiovascular evaluation and neurologic, abdominal, pelvic, and rectal exams.9,10 The pelvic exam can reveal findings such as genitourinary syndrome of menopause (GSM; also known as urogenital atrophy, vulvovaginal atrophy, and atrophic vaginitis) or POP, which can cause or exacerbate urinary symptoms. Assessment of pelvic muscle tone is done by inserting 1 or 2 fingers 2 cm into the patient’s vagina, palpating at 5 and 7 o’clock, asking the patient to tighten her rectal muscles, comparing the contralateral sides, noting her muscle strength and endurance (i.e., her ability to hold for 10 seconds), monitoring for inappropriate use of accessory muscles (e.g., abdominal or gluteal muscles), and encouraging the patient to relax her abdominal muscles.

Bladder diary

If a patient answers affirmatively to any of the screening questions posed during the history, she is asked to complete a bladder diary that will be reviewed during a subsequent visit. This diagnostic tool shows a woman’s day-to-day bladder habits and voiding patterns. She is asked to document the time, type, and amount of fluid intake (the type of fluid can indicate whether she is ingesting bladder irritants), the time of each void, each accidental leaking, and a notation of the volume of urine loss in subjective terms: large (>¼ cup), medium (<¼ cup), or small (dribbles).
Readers can access a daily bladder diary from the National Institute of Diabetes and Digestive and Kidney Diseases.11 A 3-day bladder diary is ideal.5 To evaluate the data in the bladder diary, HCPs need to be familiar with normal voiding values, which are as follows:

  • Mean 24-hour urinary output (both men and women): 1,700 mL
  • Mean number of daily voids:
    6 to 7
  • Mean bladder capacity: 330 mL (individual patients vary considerably; 300-500 mL is considered the normal range).<supP12

Vaginal pH

Without estrogen, the pH of vaginal secretions changes and the normal discharge becomes more alkaline (usually above 4.5), which is due to a decrease in vaginal lactobacilli. These changes cause vaginal tissues to thin, which can have adverse implications for the urogenital tract. Vaginal pH (normal range, 3.5-4.5) can be easily and inexpensively measured in the office by collecting a sample from the upper lateral vaginal wall and using litmus paper for pH testing.

Anita’s bladder diary indicates that, despite her best intentions, she is ingesting a host of bladder irritants, including the aforementioned cranberry pills, orange juice, green tea, and lemon seltzer. She voids 11-12 times a day and 3-4 times a night, and feels the urge to void even after she has just emptied her bladder. The exam shows that Anita has weak pelvic muscle contractions, a grade 2 cystocele, and GSM related to long-term estrogen deficiency. Her urinalysis results are negative or normal and her vaginal pH is in the alkaline range.

How is OAB identified?

The condition is identified by the presence of urinary urgency and frequency, nocturia and, in more than one-third of cases, incontinence.

Based on findings from the workup, Anita’s NP concludes that she has OAB. In addition, Anita meets diagnostic criteria for mixed urinary incontinence, urge dominant; urinary frequency; pelvic floor muscle weakness; urogenital atrophy; and chronic constipation.

What are the goals of OAB treatment?

Treatment goals are individualized and may vary from symptomatic improvement to complete symptomatic relief of urgency, frequen­cy, nocturia, and urge incontinence. Asking patients with bladder control problems about their goals before treatment begins is useful in determining how aggressive the treatment should be.

At her initial appointment, although Anita is experiencing symptoms of both urge incontinence and stress incontinence, she reports that her most bothersome complaint is the nocturia. She states that she is tired all day as a result of awakening 3-4 times per night to urinate. She has even ceased participating in certain social activities because of her fatigue. When asked about her goals for treatment, Anita asserts that she does not want surgery or “anything invasive,” and that she would be delighted if she could get more sleep and was not always rushing to get to the bathroom. She and her HCP agree that the initial phase of treatment will focus on the urge aspect of her mixed incontinence symptoms.

What constitutes first-line treatment for OAB?

Many nonpharmacologic and pharmacologic approaches are available as first-line treatment for OAB.

Lifestyle changes

One of the simplest lifestyle changes is to avoid ingesting bladder irritants, many of which appear on the Carcio “C” List (Figure). Another easy approach is to manage fluid intake. The amount of fluid intake recommended depends on each patient’s body size, temperature, and physical activity level. In general, though, most women should aim to consume 4-8 cups of fluid (water plus all other liquids) a day. They should limit the amount of fluid ingested past 6 PM (or within 5 hours of the time when they plan to go to sleep). If they are excreting pale yellow urine, they are neither under-hydrating nor over-hydrating.

Figure

Pharmacotherapy

Two different classes of drugs, anticholinergics (antimuscarinics) and a beta-3 adrenergic agonist, are approved by the FDA for the treatment of OAB with symptoms of urge incontinence, urgency, and frequency (Table). The Sidebar lists pearls to prescribing these agents.
Anticholinergics work by blocking the effects of acetylcholine at muscarinic receptors in the bladder, thereby inhibiting involuntary detrusor contractions and reducing urgency.10 Side effects such as dry mouth, constipation, and blurred vision may be bothersome enough to prompt treatment discontinuation. Side effects are generally milder with extended-release formulations. Initiating the use of artificial saliva mouthwash and instituting measures to control constipation may enhance compliance with the regimen. All of the anticholinergics have similar efficacy in clinical trials; the key is finding a particular product that an individual patient can tolerate.
The beta-3 adrenergic agonist relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of beta-3 adrenergic receptors, which increases bladder capacity.13 This agent can increase blood pressure.

Table

Other approaches to management

The AUA supports the use of behavioral therapies such as bladder training, bladder control strategies (e.g., urge suppression), pelvic floor muscle training (PFMT; also known as Kegel exercises), and fluid management as first-line therapy for all patients with OAB.9 Studies have suggested that PFMT, alone or combined with biofeedback training or electrical stimulation, may be effective for treating OAB.14-16 Avoidance of constipation, which can further weaken the pelvic floor as a result of chronic straining, is another strategy.17 Increasing the amount of dietary fiber to 30 g/day can help prevent constipation.
A vaginal pessary, a flexible device made of silicone indicated for the treatment of POP or stress urinary incontinence,17,18 can be used to treat symptoms of OAB. A retrospective parallel cohort study was conducted on women whose OAB was treated with a ring pessary or multi-component behavioral therapy (MCBT) over a 42-month period.19 The ring pessary and MCBT had similar cure rates (29 of 150 [19%] vs. 46 of 231 [20%], respectively; P = .889), regardless of whether women were premenopausal (4 of 31 [13%] vs. 14 of 68 [21%], P?=?.358) or postmenopausal (25 of 119 [21%] vs. 32 of 163 [20%]; P?=?.776). Pessaries are usually fitted by an HCP and require a prescription, but a new over-the-counter pessary is also available.
Vaginal estrogen, indicated for treatment of the symptoms of GSM, may help relieve symptoms of OAB. The epithelial linings of the vagina and urethra have the highest concentration of estrogen receptors in the body and are therefore highly sensitive to alterations in estrogen levels.20 The estradiol vaginal ring (Estring®), which works particularly well in older women, is changed every 3 months. It can be used in conjunction with a pessary, which is also changed every 3 months. Vaginal estrogen cream products include estradiol cream (Estrace® Cream) and conjugated equine estrogens cream (Premarin® Vaginal Cream), which are inserted with an applicator. These creams are considered messy by some women, but they do add lubrication. Estradiol vaginal tablets (Vagifem®), less messy than the creams, are a good choice for women with a stenotic introitus because of the smaller applicator.

Anita returns to the NP’s office after 3 weeks. She reports that she has modified her diet to decrease her intake of bladder irritants. She drinks an adequate amount of fluids each day but limits her fluid intake, with sips only, after 6 pm. She takes a daily medication to treat her OAB, and denies any dry mouth, constipation, or drowsiness. She uses a pessary, which she finds comfortable, and inserts an estradiol vaginal ring every 3 months. She takes a stool softener to reduce constipation. She has attended two pelvic floor rehabilitation sessions and does Kegel exercises at least twice daily, and she can now wait up to 2.5 hours in between voids. She needs to urinate only twice during the night and rarely experiences a leak with position changes. Although Anita wears a pad only when she goes out, for “insurance,” she really doesn’t need it any longer. As a result of this multifaceted therapeutic approach, her urinary urgency and frequency, nocturia, leaks, fatigue, and worries have all diminished.

Conclusion

Women’s healthcare providers can routinely screen their patients for symptoms of OAB. In those patients who screen positive and in whom other causes of the symptoms have been excluded, a tool such as a bladder diary can be used to identify OAB. HCPs can then educate patients about avoidance of bladder irritants and about techniques to strengthen their pelvic floor muscles. If these measures are unsuccessful, HCPs can prescribe an FDA-approved medication to further alleviate symptoms. In all cases, a treatment approach based on a woman’s own needs and goals is most likely to be successful.

References
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Articles/2002/JustHowManyBabyBoomersAreThere.aspx

2. Muller N. Anxiety and fears in women with overactive bladder. Ostomy Wound Manag. January 2013. .o-wm.com/files/owm/pdfs/OWM_January2013_Muller.pdf

3. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20(6):327-336.

4. Hartmann KE, McPheeters ML, Biller DH, et al. Treatment of overactive bladder in women. Evidence Report/Technology Assessment No. 187. 2009. ahrq.gov/clinic/tp/bladdertp.htm

5. Ellsworth PI. Overactive bladder. Medscape Drugs and Diseases. Updated April 25, 2014. emedicine.
medscape.com/article/459340-overview#aw2aab6b2b2

6. Brigham and Women’s Hospital website. Types of Incontinence and Risk Factors. Last modified on August 22, 2014. brighamandwomens.org/departments_and_services/obgyn/services/urogynecology/incontoverview.aspx

7. Carcio HA. Calming the overactive bladder: a nurse practitioner perspective. Womens Healthcare. 2014;
2(3):25-26, 49.

8. Tanagho EA, Bella AJ, Lue TF. Urinary incontinence. In: Tanagho EA, McAninch JW, eds. Smith’s General Urology. 17th ed. New York, NY: McGraw-Hill Medical. 2008:473-489.

9. Gormley EA, Lightner DJ, Burgio KL, et al; American Urological Association; Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012;188(6 suppl):2455-2463.

10. Association of Reproductive Health Professionals. Diagnosis and Management of Overactive Bladder. April 2011. arhp.org/Publications-and-Resources/Quick-Reference-Guide-for-Clinicians/OAB/Diagnosis

11. National Institute of Diabetes and Digestive and Kidney Diseases. Your Daily Bladder Diary. niddk.nih.gov/
health-information/health-topics/urologic-disease/daily-bladder-diary/Documents/diary_508.pdf

12. Parsons M, Amundsen CL, Cardozo L, et al. Bladder diary patterns in detrusor overactivity and urodynamic stress incontinence. Neurourol Urodyn. 2007;26(6):800-806.

13. Andersson KE, Martin N, Nitti V. Selective ?3-adrenoceptor agonists for the treatment of overactive bladder. J Urol. 2013;190(4):1173-1180.

14. Burgio KL. Update on behavioral and physical therapies for incontinence and overactive bladder: the role of pelvic floor muscle training. Curr Urol Rep. 2013;14(5):457-464.

15. Shamliyan TA, Kane RL, Wyman J, Wilt TJ. Systematic review: randomized, controlled trials of nonsurgical treatments for urinary incontinence in women. Ann Intern Med. 2008;148(6):459-473.

16. Liaw Y-M, Kuo H-C. Biofeedback pelvic floor muscle training for voiding dysfunction and overactive bladder. Incont Pelvic Floor Dysfunct. 2007;1:13-15.

17. Lukacz ES. Patient information: Urinary incontinence treatments for women (Beyond the Basics). UptoDate. Last updated May 11, 2015. uptodate.com/contents/urinary-incontinence-treatments-for-women-beyond-the-basics

18. Clemons JL. Vaginal pessary treatment of prolapse and incontinence. UptoDate. Last updated March 20, 2014. uptodate.com/contents/vaginal-pessary-treatment-of-prolapse-and-incontinence

19. Sze EH, Hobbs G. A retrospective comparison of ring pessary and multicomponent behavioral therapy in managing overactive bladder. Int Urogynecol J. 2014;25(11):1583-1588.

20. Brincat M, Muscat Baron Y, Galea R, Buhagiar A. Estrogen deficiency and connective tissues. In: Crosignani PG, Paoletti R, Sarrel PM, et al, eds. Women’s Health in Menopause: Behaviour, Cancer, Cardiovascular Disease, Hormone Replacement Therapy. Springer Science+Business Media Dordrecht; 1994.

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CONTINUING EDUCATION: Assessment and management of patients with obesity

PDF 50By Mary Annette Hess, PhD, FNP-BC, CNS and W. Timothy Garvey, MD, FACE

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Obesity is a disease, not a condition resulting from ill-advised behavioral choices.1 After all, obesity meets the essential criteria of a disease: It has characteristic signs or symptoms; it manifests as an impairment in the normal functioning of some aspect of the body; and it results in harm or morbidity. As such, healthcare providers (HCPs) need to identify obesity in their patients, assess each patient’s risk for obesity-related complications, begin the weight-loss discussion in a thoughtful and constructive manner, and institute an individualized management plan.

Key words: obesity, risk assessment, obesity-related complications, dietary changes, weight-loss medications

Definitions and prevalence

Obesity can be defined as a body mass index (BMI) ?30 kg/m2 or it can be suggested by a waist circumference (WC) >35 inches (in women).2 But obesity is more than just a calculation or a measurement; it is a primary disease entity that can lead to cardiometabolic, biomechanical, and other complications (Figure 1).3,4CNER_Figure 1

 

 

 

 

 

 

 

 

 

 

 

 

Here is a number that matters: Almost 80 million U.S. adults—almost 35% of the adult population in this country—meet criteria for obesity,5 with certain geographic areas and certain ethnic groups overrepresented. Prevalence of obesity is higher in southern states and some Midwestern states than in other parts of the country,6 as illustrated by this CDC map. Non-Hispanic blacks have the highest age-adjusted rate of obesity (47.8%), followed by Hispanics (42.5%), non-Hispanic whites (32.6%), and non-Hispanic Asians (10.8%).5 Although overall obesity prevalence is similar in women and men at any given age, women have a higher prevalence of class II obesity (BMI, 35.0-39.9) and class III obesity (BMI ?40).7

Risk assessment

Given the high prevalence of obesity, HCPs will likely encounter many patients in their practices who are candidates for weight management. In each case in which obesity is identified, the first step needed is to assess the patient’s risk for obesity-related complications. This assessment includes calculating BMI, measuring WC, and screening for the presence of cardiovascular disease (CVD) risk factors and co-morbidities.8 Compared with body weight alone, BMI is a better, albeit indirect, measure of adiposity, which is associated with a host of cardiometabolic abnormalities. WC, an indicator of abdominal adiposity, should be measured in patients with a BMI ?35 (the WC cutoff of >35 inches in women adds little predictive value in those with a BMI >35), including those who are overweight (BMI, 25-29.9). Women whose WC exceeds 35 inches are at increased risk for developing hypertension (HTN), type 2 diabetes mellitus (T2DM), and CVD.

Therefore, HCPs need to check patients’ blood pressure (BP) to assess for HTN and order a fasting blood glucose (FBG) test, and even a 2-hour oral glucose tolerance test and HbA1c in high-risk individuals, to assess for T2DM and pre-diabetes.9 The metabolic syndrome, which increases risk for T2DM, CVD, and stroke, is identified in women by the presence of at least three of these five risk factors: WC >35 inches, triglycerides ?150 mg/dL, high-density lipo­protein cholesterol (HDL-C) <50 mg/dL, BP ?130/85 mm Hg, and FBG ?100 mg/dL.10

Some obesity-associated diseases and risk factors place patients in a very-high-risk category for subsequent mortality.8 Patients with obesity and co-morbid coronary heart disease (CHD), other atherosclerotic diseases, T2DM, metabolic syndrome, pre-diabetes, or sleep apnea require aggressive modification of risk factors in addition to clinical management of the co-morbid disease. Furthermore, obesity has an aggravating effect on CVD risk factors such as cigarette smoking, HTN, high concentration of low-density lipoprotein cholesterol, low concentration of HDL-C, impaired FBG, family history of premature CHD, and age ?55 years (in women). HCPs need to identify these risk factors to determine the intensity of the clinical intervention that a patient requires.
Obesity takes a toll not just in terms of its effect on CVD risk, but also on cancer risk. The Cancer Research UK study showed that women with obesity had a 25% risk of developing a weight-related cancer—including cancer
of the bowel, gallbladder, uterus, kidney, pancreas, or esophagus, as well as post-menopausal breast cancer—in their lifetime.11 Cancer risk in these women was 40% higher than that in their slimmer counterparts.

Initiating the conversation

Either a patient or an HCP can initiate the conversation regarding the need to lose weight. The situation is generally easier to handle when a patient expresses a desire to lose weight. She has already acknowledged existence of the disease—that is, the obesity—and is seeking treatment for it on her own. However, in many cases, the HCP must broach the topic, usually after a patient has come in for a routine visit and the findings from her history, physical examination, and laboratory tests indicate that steps must be taken to lower her risk for experiencing obesity-related complications—or to treat the complications that already exist.

To avoid discomfiting a patient in this situation, a panel of nurse practitioners convened by the American Nurse Practitioner Foundation (ANPF) recommends that the HCP show her objective data reflecting her disease and her risk for future complications—with an emphasis that obesity is a health problem—and then assess her motivation and readiness for change.7 In this context, the HCP and the patient need to synchronize their expectations and goals for weight loss therapy. HCPs now have reliable tools to help patients lose 5%-10% of their body weight. This weight loss may not produce the desired cosmetic outcome but will no doubt result in clinical benefits. The emphasis is on improving the health of the patient.

To inspire a patient with obesity to want to lose weight and to commit to follow a weight-loss treatment plan, the HCP can help her identify at least one compelling reason to lose weight.7 Common patient-centered reasons include (1) decreasing the risk of having a complicated pregnancy; (2) being able to play with children or grandchildren; (3) walking without becoming short of breath; (4) preventing other chronic diseases such as T2DM; and (5) improving existing weight-related complications such as sleep apnea or T2DM. Of note, some patients may not be aware of the health risks posed by obesity and will be motivated to lose weight once educated about the risks.

Approach to management

Once a patient with obesity is motivated and ready to lose weight, the HCP needs to work with her to devise a management plan. Both of them should agree on the goals of weight-loss therapy and on the purpose of long-term therapy. A realistic initial goal for many patients is a loss of 5% of body weight in 3 months. Three major management options—lifestyle modification, pharmacotherapy, and bariatric surgery—can bring about weight loss and reduce obesity-related morbidity and mortality.1 This article focuses on the first two options.

Lifestyle modification

A comprehensive weight-loss program starts with lifestyle modification comprised of dietary changes, increased activity, and behavioral control.12

Dietary changes

With regard to energy intake, the ANPF recommends a reduction of 500-1,000 kcal/day, which can be accomplished by limiting portion size, reducing fat and sugar intake, and using commercial weight-loss meal replacements.7 The patient can follow one of many diets shown to be safe and effective; examples are a low-carbohydrate diet,13 a low-fat diet,14 a Mediterranean diet,15 a low-glycemic-load diet,16 and a portion-controlled diet.17

Practical dietary tips include avoiding skipping meals and consuming small meals and between-meal snacks every 3-4 hours. With regard to food intake, moderation is the watchword. With regard to fluid intake, however, drinking eight 8-oz glasses of water a day is crucial unless contraindicated (e.g., in patients with renal failure).

Choice of a particular diet is less important than making a commitment and adhering to the diet,18 although following a regimen tailored for a co-morbidity makes sense. Because compliance is the key to success, the diet plan should accommodate the patient’s personal and cultural preferences. Regardless of the diet chosen, patients should monitor their caloric intake via a food diary and weigh themselves at least once a week.19

Increased activity

Choice of a particular activity (e.g., walking, swimming) depends on a patient’s preference and access to, say, a pool, as well as her current weight and health status. An assessment of mobility, cardiovascular (CV) status, and perhaps pulmonary function is needed before a patient embarks on a new exercise program.20 The goal is to increase energy expenditure.20 Exercising for ?150 minutes/week can lead to modest weight loss and help prevent weight regain; doubling this amount will promote more robust weight loss.21 As with food intake, patients should record their daily physical activity.

Exercise not only facilitates weight loss but also improves CV health by reducing BP, lipid levels, and visceral fat. These reductions are linked to improved glucose tolerance and insulin sensitivity in persons without diabetes and improved glycemic control in patients with T2DM.12 Enhanced physical fitness may even lessen obesity-related mortality. Of note, patients with obesity must modify their diet and increase physical activity in order to lose weight and reduce their risk for obesity-related complications. Another note: In addition to traditional exercise, patients can aim to increase energy expenditure throughout the day by reducing sedentary behaviors. For example, car owners can park twice as far from store entrances as they used to; city dwellers can walk instead of taking a bus, subway, or taxi; and office workers can use a standing desk instead of sitting at their desk.

Behavioral therapy

As applied to weight loss, behavioral therapy entails techniques for helping patients replace habits that contribute to excess weight and poor health with those that promote weight loss and good health.12 Key components of behavioral therapy include frequent encounters with HCPs, education, stimulus control, cognitive restructuring, goal-setting, self-monitoring, and social support.20 Group weight-loss programs in community settings, commercial weight-loss programs, and programs delivered by telephone, the Internet, or text message can all be effective, depending on patient preference.12

Pharmacotherapy

If a patient has not lost about 5% of her body weight after 3 months, or if she has lost weight but regained some, most, or all of it over time, she and her HCP should consider use of weight-loss medication as an adjunct to lifestyle modification. In some patients with severe complications who require clinically meaningful weight loss quickly, lifestyle modification and pharmacotherapy can be initiated concomitantly.

Rationale

In all human beings, calorie restriction triggers various biological adaptations designed to prevent starvation.22 These adaptations may even be potent enough to reverse the initial weight-loss success achieved with lifestyle modification. In persons with obesity, additional biological adaptations function to preserve, or even increase, their highest sustained lifetime body weight. As such, more biologically-based interventions are likely to be needed to counter the compensatory adaptations that maintain a person’s highest lifetime body weight.22 Other reasons for pharmacologic intervention in facilitating weight loss include the following:

  • Appetite-suppressing medication enhances a patient’s ability to adhere to a reduced-calorie diet.
  • Addition of a weight-loss medication consistently achieves greater weight loss, and for a longer duration of time, than that achieved by the lifestyle intervention alone.
  • Medication can help achieve the degree of weight loss needed to treat obesity-related complications.
  • The American Association of Clinical Endocrinologists (AACE), the American Society of Bariatric Physicians (ASBP), the American Heart Association (AHA), the American College of Cardiology (ACC), and The Obesity Society (TOS) all recommend use of medication for patients with obesity and sufficient health risk.20,23,24

Principles for use

The FDA indication for use of weight-loss medications is a BMI ?30 or a BMI of 27-29.9 with at least one obesity-related complication. The medication should be stopped if weight loss is <5% after 12 weeks on a maximal dosage. If one agent is ineffective or poorly tolerated, a different one can be tried. All of these agents are contraindicated for use during pregnancy. Pharmacotherapy is individually tailored to each patient’s needs. More data are needed regarding the safety of combination therapy and the use of medications beyond 2 years.

Options

Table 1 lists FDA-approved options for treating obesity.25-31Table 2. Weight-loss medications: Clinical trial information, accessible through this link, shows the results of clinical trials demonstrating the efficacy of these agents.32-39Figure 2 illustrates the comparative efficacy of these weight-loss medications.32-36,38-45
CNe_Table 1

 

CNE Figure 2

Guidelines for practice

The spectrum of obesity treatment guidelines ranges from those that are BMI-centric, wherein treatment indication is based on BMI and the treatment goal is to lose a given amount of weight (e.g., 5%-10%), to those that are complications-centric, wherein treatment indication is based on risk for, presence of, and severity of obesity-related complications and the treatment goal is to treat or prevent the complications.46Obesity treatment guide­lines from the National Heart, Lung, and Blood Institute (NHLBI), at one end of the spectrum, are based primarily on BMI and WC, although risk factors and co-morbidities are taken into account.8 The AACE, at the other end of the spectrum, recommends (1) evaluating patients with obesity for cardiometabolic and biomechanical complications; (2) selecting (a) therapeutic targets for improvements in complications, (b) treatment modality, and (c) treatment intensity; and (3) intensifying lifestyle and/or pharmacologic and/or surgical treatment modalities for greater weight loss if therapeutic targets for improvements in complications are not met.23Table 3 lists percentages of weight loss needed to achieve therapeutic benefits with regard to various obesity-related complications.4CNE_Table3

 

The AHA/ACC/TOS obesity guideline, which is closer to that of the NHLBI, recommends (1) identifying patients who need to lose weight, based on BMI and WC; (2) informing patients with CVD risk factors that lifestyle changes that produce even modest sustained weight loss of 3%-5% can result in clinically meaningful health benefits, and that greater weight loss produces greater benefits; (3) devising dietary strategies for weight loss; (4) devising a comprehensive lifestyle program that helps patients adhere to a lower-calorie diet and increase physical activity through use of behavioral strategies; and (5) selecting patients for whom bariatric surgery is advised—that is, those with a BMI ?40 or a BMI ?35 with obesity-related conditions.24 The approach of the ASBP to obesity management, which is closer to that of the AACE, focuses on treating diseases related to increased body fat and its adverse metabolic and biomechanical consequences, which may improve patient health, quality of life, body weight, and body composition.20

Conclusion

Obesity is a disease that requires permanent lifestyle changes. Lifestyle modification, enabled by dietary changes, increased physical activity, and behavioral therapy, is implemented first. If a patient does not reach her goals in terms of reducing her weight and her risk for obesity-related complications, medication is added. Most medications suppress appetite, enhance a patient’s ability to follow a reduced-calorie diet, and enable significantly greater weight loss than that achieved by lifestyle changes alone. In addition, medication use can help sustain weight loss and prevent weight regain over time.

For patients with obesity and obesity-related co-morbidities, weight loss is used therapeutically to treat the obesity-related complications. The role of the HCP is to diagnose the disease of obesity, assess the patient’s risk for obesity-related complications, discuss weight-loss strategies and goals with the patient, support the patient in implementing these strategies and reaching these goals, and provide regular follow-up and encouragement over the ensuing months, years, and decades.

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References

  1. Mechanick JI, Garber AJ, Handelsman Y, Garvey WT. American Association of Clinical Endocrinologists’ position statement on obesity and obesity medicine. Endocr Pract. 2012;18(5):642-648.
  2. World Health Organization. Obesity and overweight. Fact sheet No. 311. Updated January 2015. http://www.who.int/mediacentre/factsheets/fs311/en/
  3. Centers for Disease Control and Prevention. Overweight and Obesity. Adult Obesity Facts. Last updated September 2014. http://www.cdc.gov/obesity/data/adult.html
  4. Daniel S, Soleymani T, Garvey WT. A complications-based clinical staging of obesity to guide treatment modality and intensity. Curr Opin Endocrinol Diabetes Obes. 2013;20(5):377-388.
  5. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311(8):806-814.
  6. Centers for Disease Control and Prevention. Overweight and Obesity. Obesity Prevalence Maps. Last updated September 2014. http://www.cdc.gov/obesity/data/prevalence-maps.html
  7. American Nurse Practitioner Foundation. Nurse Practitioners and the Prevention and Treatment of Adult Obesity. 2013. http://anp-foundation.org/wp-content/uploads/2013/07/ObesityWhitePaperv11.pdf
  8. NHLBI Obesity Education Initiative. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000. www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf
  9. American Diabetes Association. Standards of Medical Care in Diabetes—2012. Diabetes Care. 2012;35:S11-S63.
  10. Grundy SM, Brewer HB Jr, Cleeman JI, et al. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109(3):433-438.
  11. MedlinePlus. Obesity Raises Women’s Cancer Risk by 40 Percent, Study Finds. March 17, 2015. http://www.nlm.nih.gov/medlineplus/news/fullstory_151517.html
  12. Wadden TA, Webb VL, Moran CH, Bailer BA. Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation. 2012;125(9):1157-1170.
  13. Atkins RC. Dr. Atkins’ New Diet Revolution. New York, NY: Avon; 2002.
  14. Krauss RM, Eckel RH, Howard B, et al. AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000;102(18):2284-2299.
  15. Shai I, Schwarzfuchs D, Henkin Y, et al; Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359(3):229-241.
  16. Makris AP, Foster GD. Dietary approaches to the treatment of obesity. Psychiatr Clin North Am. 2005;28(1):117-139, viii-ix.
  17. Tsai AG, Wadden TA. The evolution of very-low-calorie diets: an update and meta-analysis. Obesity (Silver Spring). 2006;14(8):1283-1293.
  18. Dansinger ML, Gleason JA, Griffith JL, et al. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005;293(1):43-53.
  19. The National Weight Control Registry. http://www.nwcr.ws/
  20. Seger JC, Horn DB, Westman EC, et al. American Society of Bariatric Physicians. Obesity Algorithm: Adult Adiposity Evaluation and Treatment. 2013. www.obesityalgorithm.org
  21. Strasser B. Physical activity in obesity and metabolic syndrome. Ann N Y Acad Sci. 2013;1281:141-159.
  22. Ochner CN, Tsai AG, Kushner RF, Wadden TA. Treating obesity seriously: when recommendations for lifestyle change confront biological adaptations. Lancet Diabetes Endocrinol. 2015;3(4):232-234.
  23. Garber AJ, Abrahamson MJ, Barzilay JI, et al; American Association of Clinical Endocrinologists. AACE comprehensive diabetes management algorithm 2013. Endocr Pract. 2013;19(2):327-336.
  24. Jensen MD, Ryan DH, Apovian CM, et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 pt B):2985-3023.
  25. U.S. Food and Drug Administration. Drugs @FDA. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/
  26. Phentermine prescribing information. Drugs.com. http://www.drugs.com/pro/phentermine.html
  27. Xenical prescribing information. Genentech USA, Inc. 2013. http://www.gene.com/download/pdf/xenical_prescribing.pdf
  28. Qsymia prescribing information. Vivus, Inc. 2012-2014. https://qsymia.com/hcp/include/media/pdf/prescribing-information.pdf
  29. Belviq prescribing information. Arena Pharmaceuticals. August 2012. https://www.belviqhcp.com/media/1001/belviq_prescribing_information.pdf
  30. Contrave prescribing information. Takeda Pharmaceuticals America, Inc. 2014. http://general.takedapharm.com/content/file.aspx?filetypecode=CONTRAVEPI&CountryCode=US&LanguageCode=EN&cacheRandomizer=ef10a935-77f9-4f19-8bfd-5eefd179c8d1
  31. Saxenda prescribing information. Novo Nordisk. December 2014. http://www.novo-pi.com/saxenda.pdf
  32. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. Xenical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-161.
  33. Smith SR, Weissman NJ, Anderson CM, et al; Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245-256.
  34. O’Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring). 2012;20(7):1426-1436.
  35. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341-1352.
  36. Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297-308.
  37. Garvey WT, Ryan DH, Henry R, et al. Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. Diabetes Care. 2014;37(4):912-921.
  38. Greenway FL, Fujioka K, Plodkowski RA, et al; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376(9741):595-605.
  39. Wadden TA, Hollander P, Klein S, et al; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013;37(11):1443-1451.
  40. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). See comment in PubMed Commons below2012;20(2):330-342.
  41. Astrup A, Carraro R, Finer N, et al; NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012;36(6):843-854.
  42. Apovian CM, Aronne L, Rubino D, et al; COR-II Study Group. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21(5):935-943.
  43. Fidler MC, Sanchez M, Raether B, et al; BLOSSOM Clinical Trial Group. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96(10):3067-3077.
  44. Munro JF, MacCuish AC, Wilson EM, Duncan LJ. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J. 1968;1(5588):352-354.
  45. Ryan DH, Peterson C, Troupin B, et al. Weight loss at 6 months with V1-0521 (PEN/TPM combination) treatment. Presented at: 69th Annual Scientific Sessions of the American Diabetes Association; June 5, 2009.
  46. Garvey WT. New tools for weight-loss therapy enable a more robust medical model for obesity treatment: rationale for a complications-centric approach. Endocrine Pract. 2013;19(5):864-874.

 

Managing nausea and vomiting of pregnancy

PDF 50

By Stefanie Tyler, MSN, WHNP-BC and Jamille Nagtalon-Ramos, MSN, WHNP-BC, IBCLC

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Despite its pervasive nature and potential severity, nausea and vomiting of pregnancy (NVP) is frequently regarded as something a woman must endure—even though effective management of the condition can greatly improve quality of life, reduce risks for maternal and fetal complications, and cut healthcare and societal costs. To help healthcare providers and their pregnant patients reach these goals, this article details the scope, etiology, impact, assessment, and management of NVP.

Key words: nausea and vomiting of pregnancy, NVP, quality of life, pyridoxine, doxylamine

Scope of the problem

The traditional classification of nausea and vomiting of pregnancy (NVP)—that is, the continuum ranging from mild to moderate to severe—is inadequate to characterize this condition’s full effect.1-3 According to a recent meta-analysis, about 70% of pregnant women experience NVP, and about 1.2% suffer from hyperemesis gravidarum (HG), the most severe form of NVP.4Symptoms, including nausea, gagging, retching, dry heaving, and vomiting, may persist ‘round the clock—despite the common term morning sickness.3,5 In a recent literature review, mean onset of NVP was day 39 from the last menstrual period (LMP)6; 13% of women began to experience NVP before day 28 and 90% before day 56 (i.e., the end of week 8 after their LMP). Peak incidence of NVP occurred dur­ing weeks 7-9. By week 16, NVP ceased in 91% of women. Recent reports indicate that NVP persists beyond week 20 in 2.5%-10% of women.7,8

Etiology

To address the unpleasant symptoms of NVP and the adverse impact of the condition on quality of life (QOL), it would be useful to know the etiology. Unfortunately, although several theories have been proposed, the etiology of NVP has not yet been clearly defined.9 NVP is most likely due to a complex interplay of hormonal, metabolic, physiologic, and psychosocial factors.5 Because of the close temporal association between peak human chorionic gonadotropin (hCG) concentrations and peak NVP symptoms, one of the most likely candidates for the emetogenic stimulus arising from the placenta is the rising level of hCG or one of its isoforms.10 Other authors theorize that NVP may serve as the body’s natural mechanism for avoiding ingestion of teratogenic substances during embryogenesis.11,12

Impact

Although the etiology of NVP has not been precisely determined, its effect on pregnant women is clear. Studies utilizing a wide range of measurement tools have identified detrimental and far-reaching consequences of NVP on maternal QOL.7 In particular, women report adverse effects of NVP on physical functioning, energy, social functioning, work, performance of household duties, and parenting.13,14 A prospective study of 367 pregnant women who completed a QOL questionnaire showed that those with moderate to severe NVP had scores similar to those of women with breast cancer or myocardial infarction, and those with severe NVP had QOL likened to postnatal depression.15

In fact, studies suggest that NVP of any magnitude can jeopardize women’s mental health.15 An interesting aspect of the burden that NVP places on a woman and her psyche is that this condition is considered a normal part of pregnancy; frequent nausea and vomiting (N/V) in any other setting would be considered pathologic and worthy of evaluation, diagnosis, management, and emotional support. As a result, NVP might not be taken as seriously because it is so common and because it is temporary, leading some sufferers to feel frustrated and guilty that they are even complaining about their symptoms.16

Nausea and vomiting of pregnancy can take a physical and psychological toll on a pregnant woman, and may have an adverse effect on her partner, family members, and even co-workers. However, mild to moderate NVP has not been shown to harm the fetus and may, in fact, be associated with favorable pregnancy outcomes, particularly in terms of rates of miscarriage, congenital malformations, and preterm births.17 Of note, though, infants of HG sufferers may be born prematurely, be small for gestational age, have significantly lower birth weights, or have 5-minute Apgar scores<7.18

Assessment

The first step in assessment of a pregnant patient who reports experiencing distressful N/V is to rule out other possible causes of the N/V besides pregnancy itself. Healthcare providers (HCPs) should ask about the onset, timing, and severity of the N/V; aggravating and alleviating factors; and appearance of the vomitus.3,8 A clinical picture of a positive pregnancy test result coupled with N/V that (1) began 30-60 days after a patient’s LMP, (2) occurs nearly every day between 9 AM and noon, and (3) is relieved to some degree by eating dry foods or carbohydrates is likely to represent NVP.

Differential diagnosis

Although NVP is the most obvious diagnosis when a pregnant wom­an presents with N/V, it is not the only possibility. An important distinguishing feature of NVP is that it begins prior to 10 weeks’ gestation; N/V onset after 10 weeks usually has an alternate cause. A history and physical examination should rule out these conditions19,20:

  • Gastrointestinal disorders such as gastroenteritis, cholecystitis, hepatitis, peptic ulcer disease, pancreatitis, appendicitis, and Helicobacter pylori infection;
  • Genitourinary tract disorders such as pyelonephritis or uremia;
  • Metabolic disorders such as diabetic ketoacidosis, porphyria, Addison’s disease, and hyper/hypothyroidism;
  • Neurologic disorders such as vestibular lesions, migraines, and central nervous systemtumors; and
  • Infections and drug toxicity/intolerance.

NVP is a diagnosis of exclusion.3

Physical findings

Certain physical findings may suggest conditions other than pregnancy that are causing the N/V. These findings include abdominal pain/tenderness that precedes N/V or that is out of proportion to the N/V (although some epigastric pain secondary to prolonged retching may occur with NVP); fever, which is not present in NVP; and concurrent neurologic findings such as headache, neck stiffness, and/or changes in vision.20

Testing

When a cause of N/V other than pregnancy is suspected, HCPs should order laboratory tests for urinary ketones, blood urea nitrogen, creatinine, liver enzymes, electrolytes, amylase, and thyroid-stimulating hormone.8 Ultrasonography is recommended to check for multiple gestation or molar gestation. If other causes of N/V have been ruled out, and if a woman’s symptoms are severe and persistent, HCPs should investigate possible complications such as dehydration and thiamine deficiency.

Providers may base their initial approach to NVP management on a woman’s subjective description of her symptoms. To obtain a more complete picture, they can add objective measures that not only help define the magnitude of the problem but also help them monitor treatment response. Several objective measures are available, including the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scale,21 the Nausea and Vomiting of Pregnancy Instrument,22 the modified PUQE scale,23 the Health-Related Quality of Life for Nausea and Vomiting during Pregnancy (NVPQOL) questionnaire,24,25 and the 24-hour PUQE (PUQE-24) scale.26

Management

Clinical evidence suggests that use of antiemetics earlier in pregnancy may improve maternal QOL, prevent severe NVP—along with associated maternal and fetal complications—and reduce hospital-related costs.17,27 Because the etiology of NVP has not been determined, management is directed at symptoms. A reasonable approach, which is individually tailored, depends on symptom severity and the potential impact of treatment on the patient and the fetus. For mild to moderate NVP, dietary and lifestyle alterations may be sufficient. Some patients may prefer to try OTC (over-the-counter) or CAM (complementary and alternative medicine) therapies before progressing to pharmacologic interventions. However, pharmacologic treatment may be necessary and beneficial for some patients if symptoms persist. Patients with severe NVP may require hospitalization and extensive medical management.

Avoidance of triggers

Many women with NVP report that certain odors stimulate or exacerbate N/V. Avoiding stimuli such as pungent odors from food and perfumes or visual stimuli may alleviate their symptoms.28 A suggested strategy is to maintain a food diary, which may help determine tastes, textures, and odors that trigger N/V.

Dietary alterations

The most common dietary recommendations are to eat frequent small meals/snacks composed of high-carbohydrate, low-fat foods, with protein added to every snack and meal; and to avoid an empty stomach.19,29-31 For many women, eating dry food or carbohydrates before getting out of bed in the morning is helpful. Drinking liquids in between meals, instead of with meals, helps avoid gastric distention. Patients should be reassured that their diet during pregnancy, even if not “ideal,” will not harm the fetus.

These dietary recommendations apply to women with HG. However, in women with HG who have sustained significant weight loss, nutritional deficiencies may result in a compromised fetus or, at the least, cause some harm to the mother.31 In these cases, more aggressive interventions are needed.

OTC and CAM therapies

Systematic reviews of random­-
iz­ed and/or controlled trials have shown that pyridoxine (vitamin B6) improves mild to moderate nausea but does not significantly reduce vomiting27,32 or it has limited evidence of efficacy.5 When used as monotherapy, the initial dosage of pyridoxine is 25 mg orally every 6-8 hours; the maximum dosage suggested for pregnant women is 200 mg/day.33 A 2014 systematic review and meta-analysis of randomized trials showed that ginger, relative to placebo, improved nausea but not vomiting.34 A common dosage is powdered ginger 500-1,000 mg/day.8

Acupressure using a wristband or manual pressure at the P6 (Nei-Guan) point, located 4.5 cm above the wrist on the palmar side of the forearm, is a common treatment for NVP.35 One such wristband, PrimaBella®, has been approved by the FDA for this indication.36 However, a 2014 systematic review of randomized trials did not find P6 acupressure wristbands to be significantly more effective than placebo.5

Clinical evidence to support the efficacy of hypnosis or psycho­therapy as a primary treatment for NVP is insufficient. Supportive therapy, counseling, or a review of psychological factors in cases with persistent NVP symptoms, is recommended.

Pharmacotherapy

Dietary changes and OTC/CAM therapy, if tried, may not be sufficient in easing NVP symptoms. If so, patients may benefit from pharmacotherapy.

Doxylamine/pyridoxine

The American Congress of Obstetricians and Gynecologists has stated that pyridoxine, alone or in combination with doxylamine, an H1-receptor antagonist usually used as an antihistamine or hypnotic, is safe and effective for NVP and should be considered first-line pharmacotherapy.37 If OTC pyridoxine 25 mg TID alone is inadequate in easing symptoms, patients can add OTC doxylamine 12.5 mg (one-half tablet of Unisom SleepTabs) TID. However, this OTC regimen has its drawbacks: (1) several Unisom products are available; only one of them contains doxylamine; (2) patients must split the small 25-mg tablet in half to get the correct dose; (3) patients must take two separate pills 3-4 times a day; and (4) these immediate-release OTC formulations may not “cover” patients 24/7.3

In April 2013, the FDA approved Diclegis,® a combination of delayed-release doxylamine 10 mg and pyridoxine 10 mg, for the treatment of NVP.38 This product is the only FDA Pregnancy Category A-approved therapy specifically indicated for NVP.3,39 Diclegis is initially given as two delayed-release pills at bedtime; if symptoms are not adequately controlled, the dose can be increased to a maximum of four tablets daily (one in the morning, one mid-afternoon, and two at bedtime).3,40

A doxylamine-pyridoxine combination pill, previously called Bendectin, was removed from the U.S. market in 1983 following unfounded allegations that it caused birth defects. Since that time, numerous meta-analyses and studies have supported the safety of this product—in fact, no other agents given in pregnancy have more conclusive safety data with regard to teratogenicity.39,41 In addition, a major trial, which was requested by the FDA before it would grant approval for Diclegis, showed evidence of efficacy.42 In this double-blind study, 161 women with NVP were randomized to receive extended-release doxylamine-pyridoxine (n = 131) or placebo (n = 125) for 14 days; active treatment, as compared with placebo, resulted in a significantly larger improvement in NVP symptoms based on both PUQE score (–4.8 ± 2.7 vs. –3.9 ± 2.6; P = .006) and QOL. If delayed-release doxylamine-pyridoxine alone does not relieve patients’ symptoms to a sufficient extent, then alternate or additional interventions can be explored.

H1-receptor antagonists

Other H1-receptor antagonists besides doxylamine can be tried, including diphenhydramine (e.g., Benadryl®), dimenhydrinate (e.g., Dramamine®), meclizine (e.g., Antivert®), cyclizine (Marezine®), and hydroxyzine (e.g., Vistaril®). If any of these agents is added to dox­yl­amine or Diclegis, low doses are used to avoid compounding antihistamine side effects such as excess drowsiness. Pooled data from seven controlled trials indicated that antihistamines are effective in reducing vomiting in pregnant women and appear to have a protective effect in terms of the risk for fetal malformations.24 A pre­vious meta-analysis of 24 controlled studies enrolling a total of more than 200,000 women using antihistamines during pregnancy had shown no link of the drugs to birth defects or serious adverse maternal or fetal outcomes.43 Because no specific H1-receptor blocker dosing guidelines concerning pregnant women are available, standard adult dosages are recommended—for example, diphenhydramine 25-50 mg orally (PO) every 4-6 hours or 10-50 mg intravenously (IV) or intramuscularly (IM) every 4-6 hours as needed; meclizine 25 mg PO every 4-6 hours as needed; and dimenhydrinate 50-100 mg PO or rectally (PR) every 4-6 hours as needed.44

Dopamine antagonists

For women who do not respond to doxylamine and/or pyridoxine, another option is to substitute or add a drug from an different category such as a dopamine antagonist. Within this category are pheno­thia­zine antiemetics (e.g., prochlorperazine [Compazine®], promethazine [Phenergan®]) and meto­clopramide (Reglan®), which has antiemetic and prokinetic effects.3

A major downside of the phenothiazines is that, although effective as antiemetics, these agents can cause sedation, hypotension, dry mouth, and extrapyramidal symptoms. Although the FDA has placed phenothiazines in Pregnancy Category C, multiple observational studies of patients exposed to various these agents have failed to demonstrate an increased risk for major malformations.45

No specific dosing guidelines for the phenothiazines exist for pregnant women. Possible regimens are those established for adults and include promethazine 12.5-25 mg PO or PR every 4-6 hours as needed (promethazine has a black-box warning for severe tissue injuries with IV or subcutaneous administration) and prochlorperazine 5-10 mg PO or 10-25 mg PR every 6 hours as needed.44

In terms of metoclopramide, a Pregnancy Category B agent, the largest study to date, published in 2013, showed no increased risk for major congenital malformations with more than 28,000 first-trimester exposures.46 A randomized controlled trial comparing metoclopramide and prometh­azine for the treatment of HG showed no difference in efficacy, although metoclopramide was less sedating.47 Recommended dosing is metoclopramide 5-10 mg PO or IV every 6 hours as needed.44

5-HT3 antagonists

If NVP symptoms are still inadequately controlled, women can try a serotonin 5-hydroxytryptamine 3-receptor (5-HT3) antagonist
such as ondansetron (Zofran®), granisetron (Kytril®), or dolasetron (Anzemet®). Although these agents are used primarily for chemotherapy-related N/V, they are widely used for NVP—especially because, until early 2013, there were no FDA-approved drugs for NVP.3,48 In fact, the use of ondansetron for NVP has increased from 50,000 monthly prescriptions in 2008 to 110,000 monthly prescriptions in 2013, despite unresolved concerns regarding fetal safety (e.g., risk for cleft palate in the newborn49) and FDA warnings about serious maternal dysrhythmias.3,48

Using a large Danish birth registry, two groups of researchers reached different conclusions regarding the safety of ondansetron: Pasternak et al50 reported that ondansetron was not associated with increased rates of spontaneous abortion, stillbirth, major birth defects, preterm delivery, low birth weight, or small size for gestational age, whereas Andersen et al51 found a 2-fold increased risk for cardiac malformations.

Data from a large Swedish birth registry and a Swedish registry of prescribed drugs were reviewed to investigate the teratogenic effects of ondansetron.52 A total of 1349 infants born of women who had taken ondan­setron in early pregnancy between 1998 and 2012 were identified. Although no significant increase in risk for major malformations was found, the risk of a cardiovascular defect, particularly a cardiac septum defect, was significantly increased in infants whose mothers had taken ondansetron during pregnancy.

Information is limited regarding the effectiveness of ondansetron for treatment of NVP. The results of one study suggest that this agent can decrease vomiting but is only modestly effective in limiting nausea.53

Corticosteroids

Given the risk of maternal side effects, possible fetal risks (oral cleft, hypospadias, and other malformations), and uncertain efficacy, corticosteroids are reserved for treatment of refractory NVP or HG after the first trimester.49,54 If the benefit of treatment is thought to outweigh the risk, the recommended dosage is methylprednisolone 16 mg IV every 8 hours for 48-72 hours. Methylprednisolone can be stopped abruptly if there is no response, and tapered over 2 weeks in women who experience symptom relief.33 After IV therapy, women can follow an oral prednisone taper regimen.

Conclusion

Nausea and vomiting of pregnancy is a prevalent condition with major clinical impact for many women. After ruling out other possible causes of the N/V, HCPs can offer patients multiple therapeutic options such as dietary approaches, OTC/CAM therapies, and pharmacotherapeutic options to improve their QOL and the overall pregnancy experience. A period of time may be needed to fine-tune the therapeutic intervention that works best for each woman.

References

1. American College of Obstetrics and Gynecology. ACOG Practice Bulletin: Nausea and Vomiting of Pregnancy. Obstet Gynecol. 2004;103(4):803-814.

2. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2003;(4):CD000145.

3. Clark SM, Dutta E, Hankins GD. The outpatient management and special considerations of nausea and vomiting in pregnancy. Semin Perinatol. 2014;38(8):496-502.

4. Einarson TR, Piwko C, Koren G. Prevalence of nausea and vomiting of pregnancy in the USA: a meta analysis. J Popul Ther Clin Pharmacol. 2013;20(2):e163-e170.

5. Matthews A, Haas DM, O’Mathúna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2014;3:CD007575.

6. Gadsby R, Barnie-Adshead AM. Literature Review of Nausea and Vomiting of Pregnancy. 2011. https://www.pregnancysickness
support.org.uk/documents/NVP-lit-review.pdf

7. Wood H, McKellar LV, Lightbody M. Nausea and vomiting in pregnancy: blooming or bloomin’ awful? A review of the literature. Women Birth. 2013;26(2):100-104.

8. Niebyl JR, Briggs GG. The pharmacologic management of nausea and vomiting of pregnancy. J Fam Pract. 2014;63(2):S31-S37.

9. Patil CL, Abrams ET, Steinmetz AR, Young SL. Appetite sensations and nausea and vomiting in pregnancy: an overview of the explanations. Ecol Food Nutr. 2012;51(5):394-417.

10. Goodwin TM. What is the fundamental stimulus in NVP? Presented at: Exploring Nausea and Vomiting of Pregnancy (NVP). Sponsored by the NICHD Center for Research for Mothers and Children, Pregnancy and Perinatology Branch, Perinatology Research Branch. Bethesda, MD: September 20-21, 2000.

11. Flaxman SM, Sherman PW. Morning sickness: a mechanism for protecting mother and embryo. Q Rev Biol. 2000;75(2):113-148.

12. Swallow BL, Lindow SW, Masson EA, Hay DM. Women with nausea and vomiting in pregnancy demonstrate worse health and are adversely affected by odours. J Obstet Gynaecol. 2005;25(6):544-549.

13. Smith C, Crowther C, Beilby J, Dandeaux J. The impact of nausea and vomiting on women: a burden of early pregnancy. Aust N Z Obstet Gynecol. 2000;40(4):397-401.

14. Lee NM, Saha S. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am. 2011;40(2):309-334.

15. Lacasse A, Rey E, Ferreira E, et al. Nausea and vomiting of pregnancy: what about quality of life? BJOG. 2008a;115(12):1484-1493.

16. Munch S, Korst LM, Hernandez GD, et al. Health-related quality of life in women with nausea and vomiting of pregnancy: the importance of psychosocial context. J Perinatol. 2011;31(1):10-20.

17. Koren G, Madjunkova S, Maltepe C. The protective effects of nausea and vomiting of pregnancy against adverse fetal outcome—a systematic review. Reprod Toxicol. 2014;47:77-80.

18. Wegrzyniak LJ, Repke JT, Ural SH. Treatment of hyperemesis gravidarum. Rev Obstet Gynecol. 2012;
5(2):78-84.

19. Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. 2010;363(16):1544-1550.

20. Firoz T, Maltepe C, Einarson. A. Nausea and vomiting in pregnancy is not always nausea and vomiting of pregnancy. J Obstet Gynaecol Can. 2010;32(10):970-972.

21. Koren G, Boskovic R, Hard M, et al. Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2002;186(5 suppl understanding):S228–S231.

22. Swallow BL, Lindow SW, Masson EA, Hay DM. Development of an instrument to measure nausea and vomiting in pregnancy. J Obstet Gynaecol. 2002;22(5):481-485.

23. Lacasse A, Rey E, Ferreira E, et al. Validity of a modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scoring index to assess severity of nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2008b;198(1):71.e1-e7.

24. Magee LA, Chandra K, Mazzotta P, et al. Development of a health-related quality of life instrument for nausea and vomiting of pregnancy. Am J Obstet Gynecol. 2002;186(5 suppl understanding):S232-S238.

25. Lacasse A, Bérard A. Validation of the nausea and vomiting of pregnancy specific health related quality of life questionnaire. Health Qual Life Outcomes. 2008;9(6):32.

26. Ebrahimi N, Maltepe C, Bournissen FG, Koren G. Nausea and vomiting of pregnancy: using the 24-hour Pregnancy-Unique Quantification of Emesis (PUQE-24) scale. J Obstet Gynaecol Can. 2009;31(9):803-807.

27. Koren G, Maltepe C. Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum. J Obstet Gynecol. 2004; 24(5):530-533.

28. Gordon A, Platt J. Nausea and vomiting in pregnancy. In: Rakel D, ed. Integrative Medicine. Saunders; 2012:491-497.

29. Ebrahimi N, Maltepe C, Einarson A. Optimal management of nausea and vomiting of pregnancy. Int J Womens Health. 2010;4(2):241-248.

30. Maltepe C, Koren G. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum—a 2013 update. J Popul Ther Clin Pharmacol. 2013;20(2):e184-e192.

31. Einarson A, Maltepe C, Boskovic R, Koren G. Treatment of nausea and vomiting in pregnancy: an updated algorithm. 2007;53(12):2109-2111.

32. Tiran D. Nausea and vomiting in pregnancy: an ‘alternative’ approach to care. Br J Midwifery. 2014;22(8):
544-550.

33. Smith JA, Refuerzo JS, Ramin SM. Treatment and outcome of nausea and vomiting of pregnancy. UpToDate. Last updated October 27, 2014. http://www.uptodate.com/contents/treatment-and-outcome-of-nausea-and-vomiting-of-pregnancy

34. Viljoen E, Visser J, Koen N, Musekiwa A. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J. 2014;13:20.

35. Roscoe JA, Matteson SE. Acupressure and acustimulation bands for control of nausea: a brief review. Am J Obstet Gynecol. 2002;186(5 suppl understanding):S244-S247.

36. PrimaBella website. https://www.reliefband.com/primabella.html

37. American Congress of Obstetricians and Gynecologists. Guideline Summary: Nausea and vomiting of pregnancy. 2009. http://www.guideline.gov/content.aspx?id=10939&search=nausea+AND+pregnancy

38. FDA News Release. FDA approves Diclegis for pregnant women experiencing nausea and vomiting. April 8, 2013. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm347087.htm

39. Nuangchamnong N, Niebyl J. Doxylamine succinate-pyridoxine hydrochloride (Diclegis) for the management of nausea and vomiting in pregnancy: an overview. Int J Womens Health. 2014;12(6):401-409.

40. Diclegis Highlights of Prescribing Information. Duchesnay Inc. 2013. https://www.diclegis.com/pdf/Diclegis
_Full_Prescribing_Information.pdf

41. Madjunkova S, Maltepe C, Koren G. The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin®) for the treatment of nausea and vomiting of pregnancy. Paediatr Drugs. 2014a;16(3):199-211.

42. Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010;203(6):571.e1-e7.

43. Seto A, Einarson T, Koren G. Pregnancy outcome following first trimester exposure to antihistamines: meta-analysis. Am J Perinatol. 1997; 14(3):119-124.

44. Klasco RK, ed. DrugdexAE system. Greenwood Village, CO: Thomson Micromedex. Expired June 2006.

45. Mazzotta P, Magee LA. A risk-benefit assessment of pharmacological and nonpharmacological treatments for nausea and vomiting of pregnancy. Drugs. 2000;59(4):781-800.

46. Pasternak B, Svanström H, Mølgaard-Nielsen D, et al. Metoclopramide in pregnancy and risk of major congenital malformations and fetal death. JAMA. 2013;310(15):1601-1611.

47. Tan PC, Khine PP, Vallikkannu N, Omar SZ. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2010;115(5):975-981.

48. Koren G. Treating morning sickness in the United States—changes in prescribing are needed. Am J Obstet Gynecol. 2014;211(6):602-606.

49. Anderka M, Mitchell AA, Louik C, et al; National Birth Defects Prevention Study. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012;94(1):22-30.

50. Pasternak B, Svanström H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med. 2013b;368(9):814-823.

51. Andersen JT, Jimmenez-Solem E, Andersen NL. Ondansetron use in early pregnancy and the risk of congenital malformations. Int Soc Pharmacoepidemiol. 2013. Abstract 25, Pregnancy session 1. http://www.motherisk.org/videos/index.jsp

52. Danielsson B, Wikner BN, Källén B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol. 2014; 50:134-137.

53. Madjunkova S, Maltepe C, Farine D, Koren G. Patterns of antiemetic use among american women with nausea and vomiting of pregnancy. Obstet Gynecol. 2014b;123(suppl 1):155S.

54. Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62(6):385-392.

For readers of the online issue who wish to participate in this CE program, click here.

Practical strategies for the diagnosis and management of binge eating disorder

PDF 50
By Amy McKeever, PhD, CRNP, WHNP-BC and Laura J. Clauss, APRN, NP-C, CEDS, F-IADEP

Faculty

Amy McKeever, PhD, CRNP, WHNP-BC
Assistant Professor, College of Nursing, Villanova University, Villanova, Pennsylvania
Laura J. Clauss, APRN, NP-C, CEDS, F-IAEDP
President, CEO, and Medical Director, The Center for Eating Disorders Management, Inc., Bedford, New Hampshire

Intended audience
Nurse practitioners (NPs) and other advanced practice healthcare providers (HCPs) who care for women.

Continuing education (CE) approval period
Now through February 29, 2016

Estimated time to complete this activity
1 hour

Program description/identification of need
Gap 1: In 2013, binge eating disorder (BED) was designated as a formal diagnosis in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. BED is underdiagnosed and undertreated. NPs in women’s health are the primary HCP and contact for many women, and are positioned to identify patients with BED and provide treatment and/or referral.
Gap 2: Many HCPs, including NPs, who care for women are insufficiently educated about the etiology of BED and its association with genetic and environmental factors, as well as its prevalence in women with obesity.
Gap 3: Various pharmacologic agents have been studied with regard to their efficacy in patients with BED, many of whom have co-morbidities. HCPs need information about the usefulness of currently available and investigational agents to treat both BED and common co-morbidities.

Gaps in practice
Gap 1: NPs in women’s health, as well as other HCPs who specialize in the care of women, are well positioned to screen for and diagnose BED. This activity will better enable them to do so.
Gap 2: A multifaceted approach to treatment for BED is required. HCPs need information about appropriate treatment options, and need to know which members of the health-management team are best positioned to offer these options.
Gap 3: Many patients with BED have co-morbidities associated with obesity. Identification of pharmacologic agents that will improve symptoms of both BED and co-morbid conditions can help optimize patient outcomes.

Educational objectives
At the conclusion of this activity, participants should be better able to:
• Discuss current diagnostic criteria for BED.
• Apply effective patient–HCP communication strategies regarding BED and its effects, including those related to fertility and future pregnancy.
• Evaluate nonpharmacologic and pharmacologic approaches to BED treatment.
• Monitor patient progress, adjust treatment plans, and make referrals as appropriate.

Credit designation statement
This Activity (No. J-15-02) has been evaluated and approved by the Continuing Education Approval Program of the National Association of Nurse Practitioners in Women’s Health (NPWH) for 1.0 contact hour of CE credit, including 0.5 contact hours of pharmacology content. Each participant should claim only those contact hours that he/she actually spent in the educational activity.

Accreditor disclosure of conflicts of interest policy
NPWH policy requires all faculty to disclose any affiliation or relationship with a commercial interest that may cause a potential, real, or apparent conflict of interest with the content of a CE program. NPWH does not imply that the affiliation or relationship will affect the content of the CE program. Disclosure provides participants with information that may be important to their evaluation of an activity. Conflicts of interest were resolved according to NPWH policy prior to development of content. The faculty report that they have nothing to disclose.

Disclosure of unlabeled use
NPWH policy requires authors to disclose to participants when presenting information about unlabeled use of a commercial product or device or an investigational use of a drug or device not yet approved for any use. This monograph contains a discussion of unapproved uses for these drugs: topiramate, zonisamide, naltrexone, methylphenidate, and lisdexamfetamine dimesylate.

Disclaimer
Participating faculty members determine the editorial content of CE activities; this content does not necessarily represent the views of NPWH or Shire. This content has undergone a blinded peer review process for validation of clinical content. Although every effort has been made to ensure that the information is accurate, clinicians are responsible for evaluating this information in relation to generally accepted standards in their own communities and integrating the information in this activity with that of established recommendations of other authorities, national guidelines, FDA-approved package inserts, and individual patient characteristics.

Successful completion of this activity
Successful completion of this activity, J-15-02, requires participants to 1. Go to https://healthmonix.com/npwh/; click on “Sign In” in the right hand corner of the page. Sign in if you have an NPWH account, or create an account; 2. Go to the “NPWH E-Learning Portal” ; 3. Click on the title of this journal article; 4. Complete the posttest and evaluation; 5. Earn a score of 70% or better on the posttest to receive CE credit; 6. Print out the CE certificate if successfully completed.

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The authors discuss the etiology of binge eating disorder (BED), as well as techniques for screening and diagnosis and recommended treatments. They also describe common mental and physical co-morbidities in patients with BED and the disorder’s potential effects on reproductive health and pregnancy. Three relevant case studies—of a teenage girl, a woman in the middle of her reproductive years, and a woman nearing menopause—illustrate how healthcare providers can evaluate and manage patients with BED.

Key words: binge eating disorder, disordered eating, co-morbidities, cognitive behavioral therapy, pharmacotherapy

Binge eating disorder (BED), now included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),1 is defined as follows:

  • Recurrent and persistent episodes of binge eating
  • Binge eating episodes that are associated with three (or more) of the following:
    • Eating much more rapidly than normal
    • Eating until feeling uncomfortably full
    • Eating large amounts of food when not feeling physically hungry
    • Eating alone because of being embarrassed by how much one is eating
    • Feeling disgusted with oneself, depressed, or very guilty after overeating
  • Marked distress regarding binge eating
  • Absence of regular compensatory behaviors (such as purging)

Particularly common among females (See Cases 1, 2, and 3) and associated with obesity, BED poses physical, psychological, and social challenges that decrease health-
related quality of life (HRQOL) and increase disease burden.

Etiology

The etiology of BED is multifactorial and complex. Although associated with hedonic hunger, BED is linked less to pleasure and more to an attempt to suppress negative feelings through bingeing without purging.2 Motivation to binge likely also arises from homeostatic hunger.

Risk factors

Risk factors for BED include genetics, female gender, Caucasian ethnicity, weight concern, negative body image, childhood problems, low self-esteem and self-efficacy, low family cohesion, psychiatric morbidity, and stressful events.3,4 In addition, a community-based case–control study demonstrated that patients with BED, versus controls, were significantly more likely to report sexual abuse and repeated severe physical abuse. The typical overweight person with BED is overly concerned with body shape and weight. BED is most likely to occur in young women of high socioeconomic status in industrialized countries, but it is not limited to this population (See Cases 1, 2, and 3).

Binge-eating disorder in children and adolescents

In children and adolescents, early identification and treatment of BED is vital (See Case 1). Loss of control over eating is associated with modifiable lifestyle factors. Often considered temporary, BED is actually a long-term chronic condition often associated with co-morbid obesity. Childhood factors that increase risk for BED include obesity, self-criticism, poor self-esteem, body dissatisfaction, and emotional abuse.5 In female adolescents and young adult women, BED is associated with pre-existing depressive symptoms and an increased risk for developing mood disorders.6

Specific goals of treatment for children and adolescents include treatment of underlying depression or anxiety, improvement of self-esteem, normalization of eating patterns, promotion of physical activity, and implementation of family therapy to address family dysfunction and engage family members in supporting the patient’s recovery. BED treatment outcomes can be optimized through early detection and referral to eating disorder specialists; incorporating a multidisciplinary treatment team to address the physical, psychological, nutritional, and spiritual aspects of BED; and combining cognitive behavioral therapy (CBT), a self-help program, and, when appropriate, pharmacotherapy.

Co-morbid psychiatric disorders

Co-morbid anxiety, mood, and disruptive behavior disorders are common in patients with BED, as are obsessive-compulsive disorder, post-traumatic stress disorder, and substance abuse. Co-morbid obesity increases psychopathology, emotional eating, concerns about weight and body shape,7 and perhaps a desire for bari­atric surgery.8 Obesity and BED are common in patients with bipolar disorder. In patients with personality disorders, alexithy­mia (a personality construct characterized by the subclinical inability to identify and describe emotions in the self) correlates more highly with BED than with other eating disorders.9

A case–control study showed that patients with BED, compared with controls, reported a significantly greater number of adverse life events during the year prior to symptom onset, suggesting that the accumulation of stressful events can trigger the disorder.10 Even after weight loss and CBT, patients with BED experienced higher morning basal cortisol levels than did a control group without BED.

Effects of disordered eating patterns on reproductive health

Disordered adolescent eating patterns affect one’s development, with implications for reproductive function. Behaviors associated with risk-taking and self-harm frequently co-exist with eating disorders and increase risks for unplanned pregnancy and sexually transmitted infections. Obesity is strongly associated with conditions that adversely affect reproductive function.

In anovulatory overweight or obese women, sustained gradual weight loss will regulate menstrual cycles and increase the chance of spontaneous ovulation and conception.11Lifestyle modification has been shown to improve reproductive function.

Effects of binge eating disorder on pregnancy

Pre-pregnancy and pregnancy dietary patterns of women with BED may influence pregnancy outcomes. Many obstetricians do not query patients about weight control or disordered eating during pregnancy, and many patients do not seek treatment. Studies evaluating maternal and fetal outcomes in women with eating disorders are limited.

Women with BED during pregnancy are considered high risk. BED treatment during pregnancy is important for long-term management and reduction of harmful behaviors such as smoking; in fact, treatment during pregnancy is particularly likely to produce long-lasting results.

Pregnant patients with BED need frequent prenatal visits to discuss problems related to both nutrition and BED. Healthcare providers (HCPs) should do the following:

• Empower women to discuss weight and body-image concerns during pregnancy;
• Educate patients that uneven weight gain patterns may occur in pregnancy;
• Inform patients that controlling BED during pregnancy reduces the risk for a large-for-gestational-age newborn;
• Provide or refer for dietary support and meal planning;
• Assess and/or refer for management of psychiatric co-morbidities;
• Provide a routine postpartum visit at 1-2 weeks to monitor for relapse or exacerbation of BED; and
• Provide nutritional and dietary counseling for breastfeeding mothers and for the first 6-12 months postpartum.12

Co-morbid physical disorders

Binge eating disorder is associated with multiple physical co-morbidities, with decreased HRQOL and physical and psychosocial functioning.13 A large majority of individuals with BED receive medical treatment for co-morbidities, particularly obesity-related conditions such as type 2 diabetes mellitus (DM). Weight loss in patients with type 2 DM and BED who control their eating habits is similar to that in persons who have never experienced BED. BED may precede bariatric surgery and/or re-emerge post-surgery.

Screening and diagnosis

Assessment for eating disorders, including BED, should be part of a routine health evaluation. HCPs can use an assessment tool or pose a simple screening question in a matter-of-fact, nonjudgmental, empathetic manner to facilitate open conversation: Do you have thoughts, feelings, or behaviors regarding eating, weight, or body image that occupy most of your time or that make you feel out of control? (See Cases 1, 2, and 3.) The SCOFF Questionnaire can be useful. Practical strategies for screening and diagnosis implemented by the authors include the following:
• Use an eating disorder screening question at routine visits as patients age from childhood through the older adult years;
• Engage patients in a conversation about possible BED;
• Maintain accurate chronological weight records;
• Be familiar with DSM-5 diagnostic criteria;
• Obtain a 24-hour written food intake and feelings journal for
7 consecutive days (including weekends) and review the journals with patients;
• Assess for underlying depression or anxiety; initiate medication if indicated;
• Use physical, nutritional, and psychological findings to incentivize patients to engage in treatment;
• Avoid references to calories, weight, and dieting that may exacerbate feelings of shame or excessive focus on food;
• Advocate an approach for treatment of BED and obesity that does not center on the need for dieting but, instead, emphasizes the importance of specialized psychological, medical, and nutritional care;
• Be familiar with eating disorder specialists in your geographic area and be able to implement the referral process; and
• Confirm that patients follow through with BED treatment.

Binge-eating disorder subtypes may manifest in difficult-to-treat food addictions, which are common in patients with co-existing histories of addictive personality or substance abuse disorder. A marker of substance dependence includes consumption of high-fat/high-sugar foods.14 A food addiction symptom count (using criteria similar to those for substance abuse disorder in the DSM-5) should be obtained for these patients.15 Emotions associated with binge eating may be experienced differently by individuals from specific ethnic, racial, and cultural groups.

Treatment

The American Psychiatric Association has established levels of care guidelines for patients with eating disorders, who can be difficult to treat. Many patients with BED experience shame, embarrassment, self-disgust, depression, and guilt as a result of their eating disorder. They tend to eat secretly or alone and may hide binge foods. Patients may deny that they have an eating disorder and may be reluctant to discuss BED with their HCP. Many patients who use binge eating to deal with difficult life situations are reluctant to eliminate this behavior and do not fully commit to a treatment program. Others welcome interventions that may improve HRQOL.

Nonpharmacologic approaches
Cognitive behavioral therapy, considered a first-line therapy for BED, and interpersonal psychotherapy are effective in patients with BED (See Cases 1, 2, and 3). Other nondrug approaches usually entail a combination of a lifetime nutritional plan, assertiveness training, improved stress management, and moderate exercise to increase lean muscle mass.

Pharmacotherapy
No agent is FDA-approved for the treatment of BED. An application for an indication for lisdexamfetamine dimesylate as a treatment for BED likely will be filed soon with the FDA. Multiple pharmacologic agents have demonstrated benefits at varying dosages in trials conducted between 2005 and 2010.

Antidepressants
Antidepressants address common mood-related co-morbidities. Of note, many patients with BED consume tryptophan-containing carbohydrates that synthesize serotonin. When these patients’ serotonin levels are low, cravings commence. Antidepressants that inhibit reuptake of serotonin can help decrease compulsive/binge eating. In many patients with co-morbid depression (or if CBT is unavailable), selective serotonin reuptake inhibitors (SSRIs) can decrease bingeing (and purging) by 50%, although some patients may not respond to treatment or may relapse with SSRI dis­continua­tion.16 Bupropion has beneficial effects on weight and does not have SSRI side effects. Bupropion dosages of 300-450 mg/day have been shown to be effective.17Psychostimulants
Agents used to treat attention defi­cit hyper­activity disorder (ADHD) affect dopamine/norepinephrine systems associated with both the etiology of BED and eating behavior/reward behavior. An epide­miologic relationship between BED and ADHD has been noted in adolescents18 and adults.19 An association has also been reported between bulimia nervosa (BN) and ADHD; a small study of patients with co-morbid BN and ADHD showed the efficacy of psycho­stim­­ulant medication. An ongoing study is comparing methyl­phen­i­date with CBT in the treat­ment of BED.20Pharmacotherapy during pregnancy
Few studies have evaluated the use of psychotropic agents during pregnancy other than a large cohort evaluation of SSRIs. Additional data may guide decision making regarding the use of agents such as bupropion, methylphenidate, memantine, naltrexone, sodium oxybate, topiramate, and zonisamide in pregnant women.

Conclusion

Binge-eating disorder is a complex, multifactorial condition that requires a comprehensive and integrated course of treatment. Nurse practitioners and other advanced practice HCPs caring for women are positioned to play important roles in patient assessment and management.

References
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