Westhoff Carolyn L, Reinecke Isabel, Bangerter Keith, Merz Martin
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA.
Bayer Pharma AG, Berlin, Germany.
Contraception. 2014 Sep;90(3):272-9. doi: 10.1016/j.contraception.2014.04.018. Epub 2014 May 20.
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.
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.
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.
The EE/GSD patch provided effective ovulation inhibition, even in women with higher BMI.
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.
体重指数（BMI）可能会影响经皮激素给药导致的排卵抑制。鉴于美国肥胖症的高患病率，对这种影响进行研究很重要。
这项开放标签、非对照的2b期试验根据三个BMI组对173名年龄在18至35岁的女性进行了分层（第1组，n = 56，BMI≤30kg/m²；第2组，n = 55，30kg/m²＜BMI≤35kg/m²；第3组，n = 47，BMI＞35kg/m²）。女性使用含有0.55mg炔雌醇（EE）和2.1mg孕二烯酮（GSD）的避孕贴片。EE/GSD贴片每周使用一次，共三个28天周期（连续三周每周使用一片，随后为7天的无贴片间隔期），并通过Hoogland评分评估其对排卵的影响，Hoogland评分是一个综合评分，包括在第2和第3周期每3天进行的经阴道超声检查以及雌二醇（E₂）和孕酮水平。药代动力学参数评估是该研究的次要目的，在预处理周期、第2周期和第3周期采集血样用于分析测定EE、GSD和性激素结合球蛋白。使用日记信息和血清药物水平评估依从性。
在符合方案集中，研究期间仅发生了6次排卵，且没有参与者在两个研究周期中均排卵。第1组发生1次排卵，第2组发生3次，第3组发生2次。排卵抑制不受BMI影响；在所有组中，大多数参与者的Hoogland评分为1或2（即卵泡样结构＜13mm：第1组，BMI≤30kg/m²，第2周期为80.0%，第3周期为85.
