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.