Contraceptive efficacy and body weight: Does obesity affect the risk of failure?

避孕效果和体重：肥胖是否会影响避孕失败的风险？

• 批准号: 7135687
• 负责人: ALISON B EDELMAN
• 金额: $ 6.67万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-12 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7135687
• 关键词: blood chemistry; body composition; clearance rate; clinical research; contraceptives; drug screening /evaluation; estradiol; female; gonadotropins; human subject; hypothalamic pituitary adrenal axis; levonorgestrel; obesity; pharmacokinetics; progesterone; steroid analog; women' s health

DESCRIPTION (provided by applicant): Both obesity and unplanned pregnancies are at epidemic levels in the United States. An association between obesity and unplanned pregnancy would, therefore, constitute a significant public health concern. Recent epidemiological studies suggest that obesity may reduce oral contraceptive (OC) efficacy, and that this may be of particular concern with very low-dose OCs (i.e., ethinyl estradiol [EE] = 20 mcg]). Studies have not established what mechanisms might lead to this reduced efficacy. Our long-term goal is to identify the mechanisms leading to failure of OCs in obese women in order to improve contraceptive efficacy for these women. Our main hypothesis is that increased Body Mass Index (BMI) alters OC availability resulting in inadequate hypothalamic-pituitary-ovarian (HPO) axis suppression during OC use in obese women. In this R03 application, we propose to examine synthetic steroid metabolism and gonadotropin pulsatility in 20 ovulatory reproductive-age women [10 normal and 10 obese BMI] placed on a very low-dose OC [20 mcg EE/100 mcg levonorgestrel (LNG)], to focus on whether trends exist that are consistent with our main hypothesis. Our specific aims are: 1. to determine whether obesity affects the pharmacokinetics of OCs. The goal of this aim will be to measure peak and steady state concentrations of circulating OC dosed in a standard cyclic fashion in obese and normal BMI cohorts; (1a) focusing on the differences in EE and LNG steady state levels after one treatment cycle; (1b) the clearance rates with stopping treatment (at the start of the hormone free interval); and (1c) the time to steady state with restarting treatment (at the end of the hormone free interval); 2. To determine whether obesity impairs HPO axis suppression achieved with OC use. The goal of this aim will be to measure gonadotropin pulsatility (pulse amplitude and frequency) and ovarian response (average serum levels for estradiol [E2] and progesterone [P]) in obese and normal BMI cohorts; and 3. To compare FSH, LH, E2, and P levels obtained by blood spots (self-performed finger sticks) versus venipuncture to determine whether blood spot assays represent a reliable alternative to serum assays in reproductive research, as they would minimize the invasiveness and blood volume required in a larger study.

描述（由申请人提供）：在美国，肥胖症和计划外怀孕均处于流行水平。因此，肥胖与计划外怀孕之间的关联将构成一个重大的公共卫生问题。最近的流行病学研究表明，肥胖症可能会降低口服避孕（OC）功效，并且对于非常低剂量的OC（即乙基雌二醇[EE] = 20 MCG]），这可能特别关注。研究尚未确定哪些机制可能导致这种疗效降低。我们的长期目标是确定导致肥胖女性OC失败的机制，以提高这些妇女的避孕功效。我们的主要假设是，增加的体重指数（BMI）改变了OC的可用性，导致肥胖女性使用OC期间的下丘脑 - 垂体 - 伏安（HPO）轴抑制不足。在此R03应用中，我们建议在20个排卵性生殖年龄女性中检查合成类固醇代谢和促性腺激素的脉动性[10个正常和10个肥胖BMI] [20 MCG EE/100 McG EE/100 McG Levonorgestrel（LNG）]我们的具体目的是：1。确定肥胖是否影响OC的药代动力学。该目标的目的是在肥胖和正常的BMI队列中以标准循环方式测量循环OC的峰值和稳态浓度； （1a）重点介绍一个治疗周期后EE和LNG稳态水平的差异； （1B）停止治疗的间隙率（在无激素间隔开始时）； （1C）重新启动治疗（在无激素间隔结束时）进行稳态的时间； 2。确定肥胖是否会损害通过使用OC实现的HPO轴抑制。该目标的目的是测量肥胖和正常BMI队列中雌二醇[E2]和孕酮[P]的平均血清水平（雌二醇的平均血清水平）的促性腺激素搏动性（脉冲幅度和频率）和卵巢反应； 3。要比较血液点（自我执行的手指棍）获得的FSH，LH，E2和P水平与静脉穿刺，以确定血点测定是否代表了生殖研究中血清分析的可靠替代方法，因为它们可以最大程度地减少一项更大的研究中所需的侵入性和血液体积。