Higher Body Weight Effect on Combined Hormonal Contraceptives

Given the growing number of reproductive-aged individuals with a BMI ≥ 30 kg/m2 the impact that weight might have on hormonal contraceptive efficacy is important for public health as well as for personal health. Although it does appear that obesity adversely affects contraceptive steroid hormone pharmacokinetics (e.g., drug levels and how drugs are metabolized), [1,2] the literature has been conflicting regarding the impact on effectiveness. [3] Shaalini Ramanadhan, MD, MCR, and Alison Edelman, MD, MPH, explored the issue and found that there are few appropriately designed studies for any contraceptive method that explore the relationship between contraceptive efficacy and obesity. [4] The majority of studies are not large enough to investigate the main outcome of interest: pregnancy.

COCs

A study of 10,000 participants with obesity demonstrated that there may be a slight increased risk of pregnancy[5]  as did a meta-analysis performed by the FDA of individual study participant data. [6] Likely, obesity plays a small role in decreasing effectiveness, but the small impact is masked by the overwhelming issues of adherence. Both extended-cycle use of a 20-mcg EE COC and 21/7 use of a 35-mcg EE COC have been to found to provide better suppression of ovarian activity than 21/7 use of a 20-mcg EE COC in people with obesity. [7] or healthy individuals with obesity, COCs are identified as category 2 by the CDC Medical Eligibility Criteria (MEC), [8] and thus safe to use. For patients of any weight or BMI, COCs are still considered second-tier in terms of effectiveness, so if a highly effective method is desired, then an intrauterine device (IUD) or implant or a permanent method should be offered, advise Ramanadhan and Edelman.

Surgical interventions for obesity are an important consideration for prescribers of COCs. After bariatric surgery, fecundity and ovulation rates increase, and the CDC advises against pregnancy in the first 2 years post-surgery as pregnancy outcomes are worse. [9] No clinical trials have assessed the effectiveness of COCs used after bariatric surgery. A case series noted two COC failures in patients after sur-gery for malabsorptive procedures (biliopancreatic diversion, Roux-en-Y bypass). Nutritional deficiencies have been noted in patients after these surgeries, suggesting that COC efficacy may be adversely impacted by decreased gastrointestinal absorption. These patients can use COCs with caution (Category 3) if no other method is available or acceptable to the patient. Patients choosing to use COCs should be advised and encouraged to use a second (back-up) method. Concerns about COC effectiveness after bariatric surgery do not apply to other combined hormonal methods such as the transdermal patch and the vaginal ring. Decreased effectiveness of COCs is also not a concern for patients who have had restrictive procedures (banding, gastrectomy), for whom COCs are Category 1.

Contraceptive Patches

Body weight is associated with lower serum levels of EE and norelgestromin in contraceptive patch users. [10] Furthermore, limited evidence suggests that persons weighing more than 90 kg (198 lbs) may be at higher risk of pregnancy when using the contraceptive patch, but evidence is inconsistent. In a pooled analysis of the three pivotal trials for the Ortho Evra patch, 5 of the 15 pregnancies that occurred in patch users were in people weighing more than 90 kg, though such individuals comprised only 3% of the study population. [10] In contrast, another recent observational study found no increased risk of contraceptive failure among those contraceptive patch users with an overweight, or Category 1, 2, or 3 obese BMI, though data were combined with pill and ring user data. [11] The newly approved EE/ LNG patch (Twirla) has also been found to have decreased efficacy for higher-BMI patients. For individuals with BMI between 25 and 30, the PI was found to be 5.7 (95% CI 3.0–8.4), and for ≥ 30 the PI was 8.6 (95% CI 5.8–11.5), compared to 3.5 (95% CI 1.8–5.2) for those with BMI < 25. [12]

Vaginal Rings

There are no trials that compare efficacy of the ring between contraceptive users with and without obesity. [13,14] Two studies found similar etonogestrel levels and similar suppression of ovarian follicular development between those with and those without obesity using the ring. These therapeutic levels of hormones and the suppression of follicular development persisted for up to 6 weeks of continuous use. [14,15] 

References

1. Edelman AB, Carlson NE, Cherala G, et al. Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity. Contraception. 2009;80:119-27.
2. Westhoff CL, Torgal AH, Mayeda ER, Pike MC, Stanczyk FZ. Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception. 2010;81:474-80.
3. Lopez LM, Bernholc A, Chen M, et al. Hormonal contraceptives for contraception in overweight or obese women. Cochrane Database Syst Rev. 2016 Aug; 2016(8):CD008452. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063995/.
4. Ramanadhan S, Edelman A. Combined hormonal contraceptives (CHS). In: Cason P, Cwiak C, Edelman A, et al. Contraceptive Technology. 22nd edition. Burlington MA: Jones-Bartlett Learning, 2023.
5. Dinger JC, Cronin M, Mohner S, Schellschmidt I, Minh TD, Westhoff C. Oral contraceptive effectiveness according to body mass index, weight, age, and other factors. Am J Obstet­ Gynecol. 2009;201:263.e1-9.
6. Yamazaki M, Dwyer K, Sobhan M, et al. Effect of obesity on the effectiveness of hormonal contraceptives: an individual participant data meta-analysis. Contraception. 2015;92:445-52.
7. Edelman A, Micks E, Gallo MF, Jensen JT, Grimes DA. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev. 2014 Jul 29;2014(7):CD004695. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837850/.
8. Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR Recomm Rep. 2016;65.
9. American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 105: bariatric surgery and pregnancy. Obstet Gynecol. 2009;113:1405-13.
10. Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra™/Evra™ transdermal system: the analysis of pooled data. Fertil Steril. 2002;77:13-8.
11. McNicholas C, Zhao Q, Secura G, Allsworth JE, Madden T, Peipert JF. Contraceptive failures in overweight and obese combined hormonal contraceptive users. Obstet Gynecol. 2013;121:585.
12. Nelson AL, Kaunitz AM, Kroll R, et al. Efficacy, safety, and tolerability of a levonorgestrel/ethinyl estradiol transdermal delivery system: Phase 3 clinical trial results. Contraception. 2021;103:137-43.
13. Dragoman M, Petrie K, Torgal A, Thomas T, Cremers S, Westhoff CL. Contraceptive vaginal ring effectiveness is maintained during 6 weeks of use: a prospective study of normal BMI and obese women. Contraception. 2013;87:432-6.
14. Dragoman MV, Simmons KB, Paulen ME, Curtis KM. Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review. Contraception. 2017;95:117-29.
15. Westhoff CL, Torgal AH, Mayeda ER, et al. Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women. Am J Obstet Gynecol. 2012;207:39.e1-6.