Obesity, Oral Contraception and Ovarian Suppression

描述（由申请人提供）：80%的美国妇女使用口服避孕药（OC）的平均持续时间为5年。最低预期失效率约为1.5%，而典型使用失效率约为每年7%，两者之间存在很大差距。这一差距可能是由于不正确的使用或人群亚组中OC有效性降低所致。最近的报告表明，较重的妇女，特别是那些使用最低剂量的妇女，口服避孕药的失败率更高。最近，美国人口中肥胖的患病率在20-29岁的女性中增加到约23%，这是OC使用的高峰期。肥胖症在贫穷和少数民族妇女中最为普遍，她们已经经历了较高的避孕失败率。近几十年来，典型的OC剂量减少了约75%。OC的生理学和有效性尚未在肥胖妇女中进行评估。这是一个修订的建议，我们建议进行一项双盲随机临床试验，包括约100名正常体重妇女和100名基线排卵功能正常的肥胖妇女;我们将这些参与者随机分配到广泛使用的双相口服避孕药（30 μ g EE/150 μ g LN或20 μ g EE/100 μ g LN）。参与者将接受评估，以检测OC使用期间的卵泡发育和排卵;我们将使用经阴道超声检查评估卵巢和子宫内膜，并测量循环内源性激素（孕酮）。受试者将使用日记记录出血和不良事件。我们将使用这些数据来评估肥胖妇女是否由于卵巢抑制较少而比正常体重妇女有更高的口服避孕药失败的风险。我们将能够评估体重和剂量的差异，并评估体重-剂量亚组。我们将能够根据排卵前卵泡的发育和排卵来评估怀孕的风险。本研究将有很好的把握度来检测临床重要差异。结果可能会直接和立即影响避孕的做法。

DESCRIPTION (provided by applicant): 80% of U.S. women use oral contraceptives (OC) for an average duration of 5 years. There is a large gap between lowest expected failure rates of about 1.5% and typical use failure rates of about 7% per year. This gap may be due to incorrect use or to decreased OC effectiveness in population subgroups. Recent reports suggest greater oral contraceptive failure among heavier women, particularly those using the lowest doses. The prevalence of obesity in the U.S. population has recently increased to about 23% in women aged 20-29, peak years for OC use. Obesity is most prevalent among poor and minority women who already experience higher rates of contraceptive failure. During recent decades, the typical OC dose has decreased by about 75%. OC physiology and effectiveness have not been evaluated in obese women.This is a revised proposal in which we propose a double blind randomized clinical trial to include about 100 normal weight women and 100 obese women with normal ovulatory function at baseline; we will randomize these participants to widely used monophasic oral contraceptives (30ugEE/150ug LN or 20ugEE/100ug LN). Participants will undergo evaluation to detect ovarian follicle development and ovulation during OC use; we will use transvaginal sonograms to assess ovaries and endometrium and will measure circulating endogenous hormones (progesterone). Participants will record bleeding and adverse events using a diary. We will use this data to assess whether obese women are at higher risk of oral contraceptive failure than normal weight women due to less ovarian suppression. We will be able to assess differences by weight and by dose and evaluate weight-dose subgroups. We will be able to assess risk of pregnancy based on development of pre-ovulatory follicles and ovulation. This study will have very good power to detect clinically important differences. Results could directly and immediately affect contraceptive practice.