Untangling the literature on obesity and contraception

 

Given the growing number of reproductive-age women who are obese, the impact that weight might have on contraceptive efficacy is important for reproductive providers caring for patients, and for public health as well as for personal health in general. Generally, there are few appropriately designed studies for any contraceptive method that explore the relationship between contraceptive efficacy and obesity. 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 In this monthly update, we peek between the covers of Contraceptive Technology⁴ to learn the latest perspective on obesity’s impact on hormonal contraceptive effectiveness.

Combined oral contraceptive pills (COCs)⁵

The majority of women using contraception choose to use combined oral contraceptive pills (COCs). Therefore, the biggest public health question may be regarding the risk for decreased efficacy among obese women using the pill. The majority of studies are not large enough to investigate the main outcome of interest: pregnancy. However, a study of 10,000 women demonstrated that there may be a slight increased risk of pregnancy⁶ as did a meta-analysis performed by the U.S. FDA of individual study participant data.⁷ 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 provided better suppression of ovarian activity than 21/7 use of a 20 mcg EE COC.⁸ For healthy obese individuals, COCs are a CDC Medical Eligibility Criteria (MEC) category 2, and thus safe to use, but as most providers would likely prefer to use a lower-dose formulation to minimize VTE, an extended cycle with a 20 mcg EE COC may be more acceptable. For patients of any weight or BMI, COCs are still considered second-tier in terms of effectiveness, so if a highly effective or first-tier method is desired, then a long-acting reversible or permanent method should be recommended.

Bariatric Surgery and the impact on COC effectiveness. After bariatric surgery, effective contraceptive use is very important initially because fertility 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 2 COC failures in patients after surgery for malabsorption syndromes (biliopancreatic diversion, Roux-en-Y bypass). Nutritional deficiencies have been noted in patients after these surgeries, suggesting that COCs may also have contributed to their decreased gastrointestinal absorption. These patients can use COCs with caution if no other method is available or acceptable (category 3), and then use of a back-up method of contraception is also recommended. These patients can still use other hormonal methods including the transdermal patch or the transvaginal ring. Patients who have restrictive procedures (banding, gastrectomy) may use COCs (category 1).

Venous thromboembolism (VTE). A risk factor for VTE is obesity: obese COC users have as much as a 3-fold increased risk of VTE when compared with COC users of normal weight.¹⁰ The American College of Obstetricians and Gynecologists (ACOG) recommends caution in prescribing estrogen-containing contraception to patients over age 35 with a BMI >30,¹¹ although the U.S. MEC rates obesity as a category 2 condition.

Contraceptive implant¹²

In U.S. clinical trials for contraceptive implants, only subjects whose weights were less than 30% above their ideal body weights were enrolled. As a result, product labeling states that it is not known if those with higher BMI’s would have higher failure rates. Since those original clinical trials, many studies have investigated the pharmacokinetics and efficacy of the implant in users with BMI ≥30 kg/m²; the conclusion from each of those studies has been that the implant may be offered as a first-line contraceptive method to candidates of all BMIs. Current evidence on this issue is summarized in the following paragraphs.^13,14

The CHOICE study has provided robust data about the efficacy, safety and continuation rates of users of all ages and of all body mass indices. In that study, there was no significant difference in failure rates in users with different BMI categories. Normal and overweight users had failure rates of 0.000/100 user-years compared with a rate of 0.231/100 user-years in those who were obese.¹² However, that marginally higher Pearl Index in obese women occurred because there was 1 pregnancy in a study participant with a BMI ≥30 kg/m² who was transitioning from COC use to implant. The investigators commented that they could not be certain that the participant had taken the prior oral contraceptives correctly and concluded that a luteal phase pregnancy was the most logical explanation for the 1 observed pregnancy in the study.

Early work showed that ENG levels at 6 months were lower in those with BMI >30 kg/m², but at 1 year the levels were comparable within a wide range of BMIs.^15,16 At the end of 3 years of use, subjects with BMI ≥30 kg/m² had median etonogestrel levels of 188.2 pg/mL (range 75.9, 520.9). These levels were not any different from median level of those with normal weights, which was 193.7 pg/mL (range 118.3, 802.3). However, a few subjects with BMI ≥30 kg/m2 fell below the target 90 pg/mL level for guaranteed ovulation suppression.¹⁷ A second study confirmed that ENG levels are independent of BMI through 3 years of use.¹⁵ A review also concluded that the failure rates in users with BMIs greater than 30 kg/m² were as low as in those with normal BMIs.¹⁸

Cumulatively, evidence supports the conclusion that once the implant is in place, it provides convenient, “forgettable,” ongoing pregnancy protection that is not affected by BMI.^14,17

Injectable contraceptives¹⁹

The high progestin dose in injectable contraceptives allows use in overweight and obese patients without concern for decreased efficacy, though it often results in local and systemic side effects. Efficacy is not compromised by greater body weight. Effective contraception, even for obese (BMI >30) users. DMPA provides 3 months of highly effective contraception per injection. There is no decrease in the efficacy of DMPA among overweight or obese patients.^20,21

Continuing weight gain. Patients who gain more than 5% of their baseline body weight with early DMPA use may be at risk of continued weight gain.²² Baseline obesity appears to be a second, less powerful predictor of weight gain among adolescent DMPA users. One observational study found that at 18 months mean weight gain for obese adolescent DMPA users was 9.5kg as compared to 4kg for nonobese adolescents. This study, however did not account for early weight gain in its analyses.²³ Use of DMPA by obese adolescents is rated category 2 by the U.S. CDC Medical Eligibility Criteria for Contraceptive Use (MEC), while use by obese adult patients is considered category 1.

Contraceptive patch and vaginal ring²⁴

Contraceptive patch. Body weight is associated with lower serum levels of EE and norelgestromin in contraceptive patch users.⁵ 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, 5 of the 15 pregnancies that occurred in patch users were in women weighing more than 90 kg, though such women comprised only 3% of the study population.²⁵ In contrast, another recent observational study found no increased risk of contraceptive failure among overweight, obese, and morbidly obese contraceptive patch users, though data were combined with pill and ring user data.²⁶

Vaginal ring. No published trials compare efficacy of the ring between non-obese and obese contraceptive users.²⁷ One study found similar etonogestrel levels and similar suppression of ovarian follicular development between obese and non-obese women using the ring. Effects persisted for up to 6 weeks of continuous use.

 

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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 4] overweight or obese women. Cochrane Database Syst Rev 2016:Cd008452.
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