Obstetrics & Gynecology:
Contraceptive Failures in Overweight and Obese Combined Hormonal Contraceptive Users
McNicholas, Colleen DO; Zhao, Qiuhong MS; Secura, Gina PhD; Allsworth, Jenifer E. PhD; Madden, Tessa MD; Peipert, Jeffrey F. MD
Division of Clinical Research, Department of Obstetrics and Gynecology, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
Corresponding author: Colleen McNicholas, DO, Washington University in St. Louis , Division of Clinical Research, 4533 Clayton Ave, St. Louis, MO 63110; e-mail: email@example.com.
The Contraceptive CHOICE Project is funded by the Susan Thompson Buffett Foundation. Supported in part by the Washington University Institute of Clinical and Translational Sciences National Center for Research Resources (NCRR) grant UL1 RR024992 from the National Center for Advancing Translational Sciences and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under Award Number T32HD055172.
Financial Disclosure Dr. Madden is a former speaker for Bayer HealthCare Pharmaceuticals. The other authors did not report any potential conflicts of interest.
OBJECTIVE: To estimate weather contraceptive failure rates among combined oral contraceptive pill (OCP), patch, and vaginal ring users was associated with increasing body mass index (BMI).
METHODS: Females enrolled in a large contraceptive study offering the reversible method of their choice at no cost were followed-up for 2–3 years. We compared the failure rates (pregnancy) among users of the OCP, transdermal patch, and contraceptive vaginal ring stratified by BMI.
RESULTS: Among the 7,486 participants available for this analysis, 1,523 chose OCPs, patch, or ring at enrollment. Of the 334 unintended pregnancies, 128 were found to be a result of OCP, patch, or ring failure. Three-year failure rates were not different across BMI categories (BMI less than 25 8.44%, 95% confidence interval [CI] 6.1–11.5; BMI 25–30 11.03%, 95% CI 7.5–16.0; BMI more than 30 8.92%, 95% confidence interval 7.6–11.5). Increasing parity (hazard ratio [HR] 3.06, CI 1.31–7.18) and history of a previous unintended pregnancy (HR 2.82, CI 1.63–4.87), but not BMI, were significant risk factors for unintended pregnancy.
CONCLUSION: Overweight and obese females do not appear to be at increased risk for contraceptive failure when using the OCP, patch, or vaginal ring.
LEVEL OF EVIDENCE: II
The epidemic of obesity worldwide is continuing to grow. Current statistics estimate that 61.3% of adult females in the United States are classified as overweight, with 34.3% classified as obese.1 The remarkable growth can be best-illustrated when we compare these rates with those just 10 years ago, when only 20.8% of the U.S. female population was classified as obese.1 The increase in obesity has led to the development of subclassifications within the larger obese group as follows: class I, body mass index (BMI, calculated as weight (kg)/[height (m)]2) 30–34.9; class II, BMI 35–39.9; and class III, BMI 40 or more.2 In 2007–2008, 10.5% of females of reproductive age (age 20–39 years) were class II obese and 7.5% were class III.1
Equally discouraging is the prevalence of unintended pregnancy, which, despite widespread use of contraception, is still estimated to be 49%.3 Preventing unplanned pregnancy in obese females is especially important given the associated comorbidities and pregnancy complications. Still understudied is the role that obesity plays in contraceptive effectiveness. Most contraceptive research has been limited to females who are within 130% of ideal body weight. To date, there has been conflicting data regarding contraceptive failure rates among overweight and obese females using combined hormonal contraception (oral contraceptive pill [OCP] and the contraceptive patch and ring).4–7 Holt et al8 performed a case-control study evaluating failures of OCPs in users and suggest that being overweight may be associated with an increased risk of pregnancy while using OCPs. The methodology of this study has been challenged, however, citing recall bias as well as flaws in the design and data collection.9 Among the proposed mechanisms for increased failure rates are incomplete ovarian suppression leading to more frequent ovulation and altered bioavailability of the active drugs, perhaps because of variable rates of metabolism and clearance or differences in steroid distribution and absorption.10–12 Thus, accurate contraceptive counseling regarding failure rates in obese females is difficult.
The objective of our study was to estimate whether contraceptive failure rates were associated with increasing BMI. Our null hypothesis was that there would be no difference in failure rates with increasing BMI.
MATERIALS AND METHODS
The methodologic details of the Contraceptive CHOICE Project have been previously published13 and enrolled participants from August 2007 through September 2011. A brief description of the project and this specific analysis are described. The CHOICE protocol was approved by the Institutional Review Board at Washington University in St. Louis.
The CHOICE Project is a prospective cohort study of 9,256 reproductive-age females in the St. Louis area that was designed to promote long-acting reversible contraceptive methods by reducing cost and access barriers and by increasing knowledge. Each potential participant received standardized contraceptive counseling on all available reversible methods. This counseling included information regarding effectiveness, common side effects, and risks and benefits for each method.14 Each participant was then provided with the reversible contraceptive method of her choice at no cost for 3 years (first 5,090 participants) or 2 years (remainder of the cohort). Participants choosing OCPs could choose from various types based on their own preferences or provider recommendations. Ethinyl estradiol dose in the combined hormonal methods ranged from 20 micrograms to 35 micrograms. Participants were allowed to change methods as many times as desired during the follow-up period.
Inclusion criteria for the CHOICE Project included the following: age 14–45 years; not currently using contraception or willing to change reversible contraceptive methods; not desiring pregnancy in the next 12 months; sexually active or intending sexual activity with a male partner in the next 6 months; reside in or seeking health care in the St. Louis area; and able to consent in English or Spanish. Females were excluded if they had a history of a sterilization procedure. This analysis includes the first 7,486 participants enrolled in the CHOICE Project, of which 1,523 chose the OCP, patch, or vaginal ring at enrollment. All participants who used the OCP, patch, or vaginal ring at any point during their study enrollment and had their BMI calculated at the time of enrollment using objectively measured weight and height were included.
Participants were followed-up with telephone interviews at 3 and 6 months, and every 6 months thereafter, and received a $10 gift card for each completed follow-up survey. The possibility of contraceptive failure was assessed at each follow-up survey with questions about missed menses and the perceptions of the participants regarding the possibility of pregnancy. Any participant concerned about pregnancy was offered a clinic appointment for urine testing to determine pregnancy. All pregnancies were documented in a pregnancy log. Each participant with a documented pregnancy was then asked whether the pregnancy was planned and what contraceptive method was being used at the time of conception. A true contraceptive failure was defined as pregnancy that occurred during a period of OCP, patch, or vaginal ring use. Intended or planned pregnancies and pregnancies occurring with other contraceptive method use (or no method) were excluded.
The primary outcome of this analysis was contraceptive failure in females using the OCP, patch, or vaginal ring by BMI class. Participants were classified as being in one of four weight categories according to their BMI, as defined by the World Health Organization.15 Normal-weight woman were defined as those with BMI less than 25, overweight 25.0–29.9, obese 30.0–39.9, and morbidly obese 40 or more.
All statistical analyses were performed using STATA 11. Significance levels were set at .05. Demographic characteristics of all participants identified for this analysis are presented as frequencies, percentages, means, and standard deviations. Baseline characteristics of females in each method group (OCP, patch, and ring) were compared using χ2 and Fisher exact tests for categorical variables and Student t test for normally distributed continuous variables. Normality was evaluated by checking the distribution of the variable via histogram charts. Demographic characteristics of females also were compared across four BMI categories. Contraceptive failures across methods (OCPs, ring, and patch) were combined for the remainder of analyses. Kaplan-Meier failure curves were used to estimate the contraceptive failure rates by BMI group. The log-rank test was performed to test the equivalence of contraceptive failure rates among BMI groups. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for unintended pregnancy between different BMI categories. Because we measured distinct segments of contraceptive method use by each participant, there are correlations among different periods of contraceptive use from the same participant. To account for this correlation effect, we used robust variance--covariance estimation methods.16 Univariable analyses were conducted to evaluate crude associations between each baseline covariate and unintended pregnancy. Confounding was defined as more than 10% relative change in the association between unintended pregnancy and BMI category with or without the covariate of interest in the model. Confounders were included in the final multivariable model.
To confirm we had an adequate sample size to detect a twofold difference in failure rates across BMI groups, a post hoc sample size using nQuery software was calculated. Using the observed failure rate at 3 years of 8% in the normal-weight group as the reference, we determined that 274 distinct periods of OCP, patch, or ring use per BMI group would be required to achieve 80% power with an α error of 0.05. We combined our obese and morbidly obese groups to maintain 80% power for our analyses.
From August 2007 through May 2011, we identified 334 unintended pregnancies, of which 128 were attributed to OCP, patch, or vaginal ring failure. Table 1 describes the demographic characteristics of females choosing the OCP, patch, or vaginal ring at enrollment by method type. The demographic characteristics of OCP and ring users were similar. The OCP and ring users were more likely to be white, educated, nulliparous, and to have private insurance than were patch users. Patch users were more likely to be black, to have less education, no insurance, higher parity, and a history of unintended pregnancy and abortion, and to report low socioeconomic status. Despite demographic differences, 1-year contraceptive failure rates among the three methods were similar (OCP 5.6%, patch 4.6%, vaginal ring 3.4%; P=.22). In addition, no statistically significant interactions were found between contraceptive method and BMI; thus, the three methods were combined for analysis across BMI categories.
Table 2 describes demographic and reproductive characteristics of participants by BMI category. Normal-weight females (n=1,476) contributed 1,473 woman-years of OCP, patch, or vaginal ring use. Overweight females, BMI 25–30 (n=817), contributed 694 women-years of OCP, patch, or vaginal ring use. Obese females, BMI 30–40 (n=702), contributed 572 women-years of OCP, patch, or vaginal ring use. And, finally, morbidly obese females, BMI 40 or more (n=171), contributed 124 women-years of OCP, patch, or vaginal ring use. As BMI category increased, so did the mean age. Overweight, obese, and morbidly obese females were more likely to be black, have less education, lower socioeconomic status, higher parity, and a history of unintended pregnancy and abortion.
The total number of failures and cumulative failure rates per year for 3 years by BMI class are presented in Table 3. As expected, the cumulative failure rates increase with each year but do not appear to differ across BMI categories (3-year contraceptive failure range: 8.4–11.0%, 95% confidence interval [CI] 6.1–16.0%). The probability of contraceptive failure using log-rank testing was not different (P=.34) when BMI classes are compared (Fig. 1).
Table 4 shows the crude and adjusted risks of contraceptive failure associated with BMI and participant characteristics. For the final model, obese and morbidly obese classes were combined. We found no difference in the risk of unintended pregnancy by BMI class. Whereas older age was negatively associated with unintended pregnancy (HR 0.9, CI 0.85–0.95), increasing parity (HR 3.06, CI 1.31–7.18), and history of unintended pregnancy (HR 2.82, CI 1.63–4.87) remained significant risk factors for contraceptive failure.
We found no difference in contraceptive failure rates among females using the OCP, patch, or vaginal ring across BMI categories. Contraceptive failure is influenced by many factors, including compliance, frequency of intercourse, ovulatory function, and the inherent efficacy of the contraceptive method. The potential risk of combined hormonal contraceptive failure with increasing BMI is not well-understood, but it is extremely important as the epidemic of obesity continues to grow, and pregnancy in this population is associated with significant maternal and neonatal morbidity.17–22 Although there may be sound biologic plausibility for theories of increased failure rates among obese females,10,23 we did not find clinically important differences in contraceptive failure rates with increasing BMI.
Our findings support previous studies that have been limited by self-reported BMI and contraceptive use as well as small numbers of obese participants.24–26 One possible explanation for the similar effectiveness of combined hormonal contraceptives is that fertility is reduced with increasing BMI.22,27–29 Efficacy of the OCP, patch, or vaginal ring in overweight and obese females, even if reduced compared with normal-weight females, results in similar levels of pregnancy protection compared with those of normal-weight women with intact fertility. Although understanding the mechanism by which reversible contraceptives work in obese females may be important, it is more critical to be able to assure females that their risk of pregnancy when using these methods is not increased because of their BMI.
Strengths of our study include the large sample size of overweight and obese females, prospective design, objective assessment of weight and BMI, and prospective assessment of contraceptive failures. There are few reports assessing clinical outcomes in females who are more than 130% of ideal body weight, and this study begins to fill that knowledge gap. The prospective design of the Contraceptive CHOICE Project incorporates assessment of contraceptive use through different sources (frequent subjective follow-up surveys and objective pharmacy data). Coupling this with low rates of loss to follow-up (18% at 3 years) allowed for accurate classification of typical (real-world) method failure resulting in pregnancies.
Our study is not without limitations. As an observational study, the possibility of residual confounding still exists. The number of patch users in our cohort is limited, and these females have different demographic characteristics than OCP or vaginal ring users. In addition, the demographic characteristics of CHOICE participants may differ from other populations, therefore limiting the generalizability of our findings. However, our adjusted analysis demonstrated no effect of BMI on contraceptive effectiveness even after controlling for baseline differences. The sample size of our BMI groups exceeded the calculated sample size required to detect a clinically significant twofold difference, with the exception of the morbidly obese group (BMI 40 or more). This group contributed 124 female-years of OCP, patch, or ring use, translating into a power of 68% to detect a twofold difference in contraceptive failures in this group. It is important to note that there were only four contraceptive failures in the morbidly obese group using combined hormonal contraception over the 3 years. As is true with many contraceptive studies, we have relied on self-reported correct use of the method. Females experiencing pregnancy in the CHOICE Project were asked whether the pregnancy was planned and, if unplanned, what method of contraception they were using at the time. Those reporting no method use were excluded from the analysis. Additionally, we do not have information of specific OCP dosing. It is reasonable to think that OCPs with lower ethinyl estradiol could be less effective in females as BMI increases. Finally, pregnancy risk is affected by many things, including frequency of sexual activity. We did not present data on the frequency of intercourse among all females in the CHOICE Project by BMI; however, previous research has shown no differences in sexual behaviors between BMI categories.30
In conclusion, our findings are encouraging in that we found there is no difference in failure rates among overweight, obese, and morbidly obese OCP, patch, or vaginal ring users. Based on these data, there is no evidence to support a change in contraceptive counseling for females based on BMI alone. However, we previously have shown that failure rates for these methods are far greater than those for long-acting reversible contraceptive methods such as the implant and intrauterine device;31 thus, long-acting reversible contraceptive methods should be first-line contraceptive options for all females. The OCP, patch, and ring remain excellent second-tier methods. Overweight and obese females do not appear to be at increased risk for contraceptive failure when using combined OCPs, patch, or vaginal ring.
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