Do We Have a Problem? Obesity and Contraception
By Alison Edelman MD, MPH, Associate Professor, Assistant Director, Family Planning Fellowship, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, is Associate Editor for OB/GYN Clinical Alert.
Dr. Edelman reports that she is a subdermal implant trainer for Merck.
As U.S. waistlines continue to grow, so does the concern regarding obesity's effects on health and health care.1-2 Our country is also battling epidemic levels of unplanned pregnancies — approximately 50% of all pregnancies.3 If an interaction exists between the two, this could constitute a significant public health issue. Obesity is known to increase the morbidity and mortality of pregnancy outcomes and maternal health,4,5 but maternal obesity also has a long-term negative impact on the future health of any offspring — with higher rates of obesity, hypertension, and diabetes.6-8 The ability to avoid, plan, or space pregnancies through the use of contraception is an important tool for women with chronic medical problems like obesity. However, what do we know about the effectiveness or safety of contraceptives in obese women?
Is Contraception Less Effective in Obese Women?
In 2001, a retrospective cohort study sounded the alarm that obesity might adversely affect contraceptive effectiveness, with obese users being at increased risk for failure.9 A follow-up prospective cohort study from the same authors confirmed these findings.10 However, cohort studies do not prove causality or mechanism of action. Is it plausible that contraception might not work as well in obese women? For a contraceptive method to be less effective, one or more components of the following equation needs to be impaired:
Although much speculation has been made regarding the possible socio-behavioral differences between women of obese and normal BMI,11 to date no differences in drug compliance or continuation and/or coital frequency have been found. Granted all of these indices can be difficult to study and to track and may vary for different populations or age groups (i.e., teens).12,13 Recently, a study suggested that obese women might be less compliant with birth control pills based on testing drug trough levels.14 Obesity was strongly associated with a lower socioeconomic status, making it unclear which characteristic actually might impact compliance. Drug levels are known to be lower in obese women; perhaps the trough levels were too low to accurately detect.15,16 The final piece of the equation before we move on to inherent drug efficacy is fecundity. Fecundity can be affected by extremes of weight but the majority of women, whether of obese or normal BMI, are able to get pregnant.17
The mechanism of action for contraceptive methods like sterilization, intrauterine devices (IUDs), and barrier methods is mostly mechanical or local in nature and thus should be unaffected by body weight.18 The one caveat is that procedure-based contraceptive methods like sterilization and IUDs may be more difficult for the operator to complete or place.18 As these two methods are highly effective, failure to complete a sterilization procedure or place an IUD would relegate a woman to a contraceptive method with known lower efficacy.
Hormonal contraceptive methods, on the other hand, all rely on the achievement of a certain threshold effect on the hypothalamic-pituitary-ovarian axis, endometrium, and cervix to provide contraception. Currently all of our hormonally based contraceptive agents are "one-size-fits-all."17 The amount and level of suppression is based largely on the progestin component and is dose dependent. For example, lower dosed agents like the progestin-only pill cause endometrial thinning and thickening of the cervical mucus but not inhibition of ovulation, whereas a higher dose agent like the medroxyprogesterone acetate injection does all three. Can we expect the same for our obese patients? Unfortunately, hormonal contraception was never studied in women above 130% of ideal body weight,18 which unfortunately is now 30-60% of our population, and the incidence of BMIs > 35 kg/m2 appears to be growing.1,2
To determine if the efficacy of hormonal contraceptive methods are impaired in obese women, pregnancy would be the best outcome to examine. Although pregnancy is a discrete outcome on which to focus, it is hard to study because large numbers of women are needed. There are no published studies with significant numbers of obese women for hormonal contraceptive methods like pills/patch/ring, the medroxyprogesterone acetate injection, or the etonorgestrel subdermal implant.19-28 The only FDA packaging that lists weight (90 kg or higher) as a potential factor for decreased efficacy is the contraceptive patch; however, the patch studies actually showed increasing pregnancies in women who weighed ≥ 74 kg.20 These studies were not powered (i.e., sample size too small) to determine if the increased failure rate was true or just a random occurrence.
Secondary measures, such as drug levels or pharmacokinetics, do appear to be different in obese women as compared to women of normal BMI, but it is unknown if this correlates with increased contraceptive failure rates. The most concerning finding is that with a new start or following a traditional 7-day placebo week, it takes twice as long to reach a drug's steady state level in an obese woman (10 days) compared to a woman with a normal BMI (5 days).15 A drug's steady state level typically is higher than the threshold level to obtain contraceptive effect, but that does not change the fact that it would take twice as long to get there. Even for normal BMI women, prolonging the placebo week appears to be the worst time to miss pills, placing a woman at greatest risk for contraceptive failure. A recent large postmarketing study based in Europe and the United States also demonstrates lower failure rates in pills with a shorter placebo week (3 days) vs the traditional 7 days.29 One could easily make the leap that for any woman whether of obese or normal BMI that a shorter or no placebo week decreases contraceptive failures.
So where does this leave us? We may not have the exact answer to the question "does obesity influence contraceptive effectiveness," but I argue that we can still counsel women no matter what their weight in the same way:
- Offer the most effective options first — long-acting reversible methods or permanent contraception for those finished with childbearing.
- Consider shortening the placebo week for the pill/patch/ring or even eliminating the placebo week in the pill/ring (most experts agree that they would not recommend eliminating the placebo week for the patch).
- The use of contraception prevents more pregnancies than the use of no contraception.
Is Contraception Safe in Obese Women?
Perspective is always important when discussing risks. For contraceptive use, the "perspective" is pregnancy. The risks of pregnancy and the postpartum almost always trump the risk of contraceptive use in a woman with almost any chronic medical problem including obesity. This does not mean that contraceptive use is without risk, but the risk of contraceptive use is significantly lower compared to pregnancy and especially the postpartum state. Yet many clinicians have difficulty with this comparison since we play an active role when prescribing a contraceptive method, which places some of the "burden of risk" upon us (i.e., liability concerns); whereas pregnancy is a "natural" process where the "burden of risk" falls completely on the patient. This may be short-sighted, as a high-risk pregnancy places an even greater magnitude of risk upon us, the patient, her family, and the system.
Luckily, we now have evidence-based guidelines through the Centers for Disease Control (CDC). These guidelines will be regularly updated providing help in risk stratifying our patients with chronic illness like obesity.30 The CDC guidelines categorize risk into four subgroups: category 1 (no restrictions for use), category 2 (advantages of use generally outweigh risk), category 3 (the risks usually outweigh the advantages), category 4 (unacceptable health risk). Since the obese are at increased risk of thromboembolic events at baseline, contraceptive use adds an additional risk that must be considered. For a healthy obese woman with no other cardiovascular risk factors, the CDC medical eligibility criteria for contraceptive use rates all methods of contraception a category 1 except for combined hormonal methods (pills/patch/ring), which get a category 2.30 A large federally sponsored review of female sterilization procedures also found that there were slightly higher complication rates for obese women undergoing sterilization procedures as compared to a normal BMI woman — mostly wound infections.31 This review only addressed sterilization procedures performed via an abdominal approach. It is unknown if complications are higher with transcervical sterilizations in an obese patient.32
And just to come full circle and get back to perspective, studies show that the risk of venous thromboembolism (VTE) in an obese woman on combined oral contraceptives appears similar to the risk of VTE in a pregnant woman of normal BMI.18 Although your counseling of risk might change slightly with an obese vs a normal BMI patient who is otherwise healthy, your options of what to offer her for contraception should not.
- World Health Report 2002. Overweight, Obesity, and High Body Mass. Page 60. Available at: http://www.who.int/whr/2002/en/whr02_en.pdf. Accessed Jan. 27, 2009.
- Hedley AA, et al. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004;291:2847-2850.
- Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health 2006;38:90-96.
- Rode L, et al. Obesity-related complications in Danish single cephalic term pregnancies. Obstet Gynecol 2005;105: 537-542.
- Nohr E, et al. Prepregnancy obesity and fetal death: A study within the Danish national birth cohort. Obstet Gynecol 2005;106:250-259.
- Catalano PM, Ehrenberg HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG 2006;113:1126-1133.
- Boney CM, et al. Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005;115:e290-6.
- Whitaker RC. Predicting preschooler obesity at birth: The role of maternal obesity in early pregnancy. Pediatrics 2004;114:e29-36.
- Holt V, et al. Body weight and risk of oral contraceptive failure. Obstet Gynecol 2002;99:820-827.
- Holt V, et al. Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol 2005;105:46-52.
- Kaneshiro B, et al. Body mass index and sexual behavior. Obstet Gynecol 2008;112:586-592.
- Halpern CT, et al. Effects of body fat on weight concerns, dating, sexual activity: A longitudinal analysis of black and white adolescent girls. Dev Psychol1999;35:721-736.
- Wingood GM, et al. Body image and African American females' sexual health. J Womens Health Gend Base Med 2002;11:433-439.
- Westhoff C, et al. Predictors of noncompliance in an oral contraceptive clinical trial. Contraception 2011;84:329.
- Edelman AB, et al. Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity. Contraception 2009;80:119-127.
- Westhoff C, et al. Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception 2010;81:474-480.
- Speroff L, et al. Clinical Gynecologic Endocrinology and Infertility. 6th edition. Lippincott Williams & Wilkins. Baltimore, MD; 1999.
- Edelman A. Society of Family Planning Clinical Guidelines: Contraceptive Considerations in Obese Women. Contraception 2009;80:7.
- Audet MC, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: A randomized controlled trial. JAMA2001;285:2347-2354.
- Zieman M, et al. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: The analysis of pooled data. Fertil Steril 2002;77: S13-18.
- Dieben T, et al. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol 2002;100:585-593.
- Westhoff C. Higher body weight does not affect Nuvaring's efficacy. Obstet Gynecol 2005;105;56S.
- Roumen FJ, et al. Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol. Hum Reprod 2001;16:469-475.
- Croxatto H, Mäkäräinen L. The pharmacodynamics and efficacy of Implanon: An overview of the data. Contraception 1998;58(6 Suppl):91S-97S.
- Huber J. Pharmacokinetics of Implanon: An integrated analysis. Contraception 1998;58(6 Suppl):85S-90S.
- Jain J, et al. Contraceptive efficacy and safety of DMPA-SC. Contraception 2004;70:269-275.
- Personal communication with Schering-Plough, Kenilworth, NJ. March 25, 2009.
- Graesslin O, Korver T. The contraceptive efficacy of Implanon: A review of clinical trials and marketing experience. Euro J Contra Reprod Health Care 2008;13(Suppl 1):4-12.
- Dinger J, et al. Effectiveness of oral contraceptive pills in a large U.S. cohort comparing progestogen and regimen. Obstet Gynecol 2011;117:33-40.
- Centers for Disease Control. U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. MMWR 2010. Available at: http://www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf. Accessed Nov. 1, 2011.
- Jamieson DJ, et al. Complications of interval laparoscopic tubal sterilization: Findings from the United States Collaborative Review of Sterilization. Obstet Gynecol 2000;96:997-1002.