Impact of body mass index on suppression of follicular development and ovulation using a transdermal patch containing 0.55-mg ethinyl estradiol/2.1-mg gestodene: a multicenter, open-label, uncontrolled study over three treatment cycles.

BACKGROUND: Body mass index (BMI) may influence ovulation inhibition resulting from transdermal hormone delivery. Investigation of this effect is important given the high prevalence of obesity in the US. STUDY DESIGN: This open-label, uncontrolled, Phase 2b trial stratified 173 women (18-35 years) according to three BMI groups (Group 1, n = 56, ≤ 30 kg/m²; Group 2, n = 55, > 30 kg/m² and ≤ 35 kg/m²; and Group 3, n = 47, > 35 kg/m²). Women used a contraceptive patch containing 0.55-mg ethinyl estradiol (EE) and 2.1-mg gestodene (GSD). The EE/GSD patch was used weekly for three 28-day cycles (one patch per week for 3 consecutive weeks followed by a 7-day, patch-free interval), and its effect on ovulation was assessed by the Hoogland score, a composite score that comprises transvaginal ultrasound and estradiol (E2) and progesterone levels every 3 days in Cycles 2 and 3. Evaluation of pharmacokinetic parameters was a secondary aim of the study, and blood samples for analytic determination of EE, GSD and sex hormone-binding globulin were taken during the pretreatment cycle, Cycle 2 and Cycle 3. Compliance was assessed using diary information and serum drug levels. RESULTS: In the per-protocol set, there were only six ovulations during the study, and no participant ovulated in both study cycles. One ovulation occurred in Group 1, three in Group 2 and two in Group 3. Ovulation inhibition was unaffected by BMI; in all groups, most participants had Hoogland scores of 1 or 2 (i.e., follicle-like structures < 13 mm: Group 1, ≤ 30 kg/m², 80.0% in Cycle 2, 85.7% in Cycle 3; Group 2, > 30 kg/m² and ≤ 35 kg/m², 61.4% in Cycle 2, 75.0% in Cycle 3; Group 3, > 35 kg/m², 78.0% in Cycle 2, 72.5% in Cycle 3). Serum levels of follicle-stimulating hormone, luteinizing hormone, E2 and progesterone were similar between groups. Body weight had a limited effect on EE clearance that was unlikely to be clinically relevant. CONCLUSION: The EE/GSD patch provided effective ovulation inhibition, even in women with higher BMI. IMPLICATIONS: This is the largest-to-date study of physiologic endpoints and found no clinically important differences in ovarian suppression among obese and normal-weight users of the EE/GSD contraceptive patch, thus providing reassurance that obese women can achieve the same high level of contraceptive protection as normal-weight users.