Elsevier

Contraception

Volume 93, Issue 1, January 2016, Pages 52-57
Contraception

Original research article
Body mass index does not affect the efficacy or bleeding profile during use of an ultra-low-dose combined oral contraceptive,☆☆

https://doi.org/10.1016/j.contraception.2015.09.013Get rights and content

Abstract

Objectives

Safe and effective contraceptive options for obese women are becoming more important due to the obesity epidemic within the United States. This study evaluated the impact of body mass index (BMI) on efficacy, safety and bleeding patterns during use of an ultra-low-dose combined oral contraceptive (COC).

Study Design

Data are from a Phase 3 clinical efficacy and safety study of an ultra-low-dose COC containing 1.0-mg norethindrone acetate and 10-mcg ethinyl estradiol. Pearl Indices, adverse events and bleeding profile were calculated for BMI ranges of < 25, 25–30 and > 30 kg/m2.

Results

Of the 1581 participants included in the analysis, 28.3% were overweight, and 18.0% were obese. For women aged 18–45 years, the Pearl Indices were 2.49, 2.32 and 1.89 for women with a BMI < 25, 25–30 and > 30 kg/m2, respectively. The ultra-low dose of ethinyl estradiol did not impact scheduled bleeding or intensity of bleeding, but we observed a slight decline in amenorrhea and slight increase in unscheduled bleeding in obese women compared with other BMI categories.

Conclusions

Our analysis of an ultra-low-dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI.

Implications

Our analysis of an ultra-low ethinyl estradiol dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI. An ultra-low-dose COC provides another safe and effective contraceptive option for obese women.

Introduction

Sixty-six percent of adult women aged 20 years or older in the United States are classified as overweight, with 36.5% classified as obese [1]. Assisting women in making the selection of a safe and effective contraceptive option can be challenging for healthcare providers. As the incidence of obesity increases, understanding the efficacy and potential risks of combined oral contraceptives (COCs) with increasing BMI is extremely important. Obese women are almost twofold likely as normal-weight women to experience a venous thromboembolism, and obese women using COCs are more likely to experience a venous thromboembolism than obese women who are not users [2], [3]. Pregnancy and delivery, however, represent a greater risk of thromboembolism than use of COC [4], [5]. Therefore, preventing unplanned pregnancy in obese females is very important due to the associated pregnancy comorbidities and complications [5], [6], [7].

The estrogen component of COCs is specifically associated with cerebrovascular complications, thromboembolic incidents and myocardial infarction [8]. The risk of thrombotic stroke and myocardial infarction in women increases with age and is important in the consideration of COC [9]. There was a small difference in the risk of stroke and myocardial infarction between COC users of 30–40-mcg and 20-mcg ethinyl estradiol (EE), but BMI was not reported [9]. Estrogen doses have decreased in modern COCs without affecting overall efficacy [10], their efficacy is primarily controlled by the progestin component and the estrogen component primarily controls irregular (unscheduled) endometrial bleeding. Further improvements in efficacy and bleeding control of low-dose estrogen COCs have been demonstrated by decreasing the hormone-free interval [11]. There is one ultra-low-dose COC available that contains 10-mcg EE and has a 24/2/2 dosing regimen with 24 days of active pills, followed by 2 days 10-mcg EE, and another 2 days of inactive (hormone-free) ferrous fumarate tablets (Lo Loestrin® Fe, Actavis Pharma, Inc., Parsippany, NJ, USA).

We conducted a post-hoc analysis of the previously published Phase 3 study of the ultra-low-dose COC [12] to examine efficacy, safety and the bleeding profile by body mass index (BMI) category [normal weight (BMI, ≤ 24.9), overweight (BMI, 25–29.9) and obese (BMI, > 30)]. Previously published analyses evaluating the impact of increasing BMI on COCs have focused on COCs with higher estrogen doses (≥ 20 mcg) and have primarily examined the effects on efficacy.

Section snippets

Materials and methods

A complete description of the Phase 3, open-label, uncontrolled, multicenter study of an ultra-low-dose COC regimen has been previously reported [12]. The study population included heterosexually active women aged 18–45 years with a BMI (calculated as weight (kg)/[height (m)]2) ≤ 35, a negative serum pregnancy test and a willingness to use the study drug as the only method of contraception. Serum and urine pregnancy tests were performed at Visits 1 and 8; urine pregnancy tests were performed at

Results

There were 1581 participants in the modified intent-to-treat population, 18–45 years of age, included in the analysis. Of these, 53.7% were normal-weight, 28.3% overweight and 18.0% obese. Baseline demographics and patient characteristics (Table 1) were similar between groups with respect to age and smoking status. Although the number of obese women enrolled was lower than the number of normal-weight or overweight women, we observed a trend toward more Black women and new COC users in the obese

Discussion

Our post-hoc analysis of an ultra-low-dose COC found no clinically important differences in contraceptive failure rates with increasing BMI in women between 18–35 and 18–45 years of age. Our findings are consistent with outcomes of other low-dose COCs. Westhoff et al. found no effect of weight on contraceptive efficacy with use of 100-mcg levonorgestrel/20-mcg EE for 84 days followed by 10-mcg EE for 7 days for up to 1 year of use [13]. Zhang et al. found that higher body weight and BMI are not

Acknowledgments

This study was sponsored by Actavis, Inc. Statistical analyses were provided by Edenridge Associates, LLC, and supported by Actavis, Inc. Medical editorial assistance was provided by William Sinkins, PhD, of ProEd Communications, Inc., and was supported by Actavis, Inc.

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  • Cited by (0)

    Role of the Funding Source: This study was sponsored by Actavis, Inc. The sponsor was involved in study design, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication.

    ☆☆

    Clinical Trials Registration Number: NCT00391807.

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