Improving Contraceptive Effectiveness in Obese Women

提高肥胖女性的避孕效果

• 批准号: 7696945
• 负责人: ALISON B EDELMAN
• 金额: $ 63.91万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7696945
• 关键词: Age; Animals; Area Under Curve; Binding; Biological Markers; Body mass index; CYP2C9 gene; Cervix Mucus; Cervix Uteri; Characteristics; Contraceptive Agents; Contraceptive Usage; Data; Development; Dose; Drug Kinetics; Enzymes; Epidemic; Epidemiologic Studies; Estradiol; Ethinyl Estradiol; Failure; Fatty acid glycerol esters; Goals; Gonadotropins; Grant; Half-Life; Hepatic; Hormonal; Hormones; Intervention; Life; Measures; Metabolism; Monitor; Obesity; Oral Contraceptives; Organ; Ovarian; Ovarian Ablation; Ovarian hormone; Ovary; Ovulation; Pharmaceutical Preparations; Phenotype; Pituitary Gland; Placebos; Population; Pregnancy; Progesterone; Public Health; Randomized; Safety; Sampling; Secondary to; Serum; Sex Hormone-Binding Globulin; Steroids; Testing; Therapeutic; Thrombosis; Time; Treatment Protocols; Ultrasonography; United States; Unplanned pregnancy; Upper arm; Woman; base; cohort; contraceptive effectiveness; contraceptive efficacy; drug clearance; enzyme activity; experience; health economics; hypothalamic pituitary ovarian axis; improved; pill; prevent; reproductive; response; steroid hormone; steroid hormone metabolism; unintended pregnancy

Contraceptive failure is the primary cause of unintended pregnancy in the United States. With obesity rates at epidemic proportions, any association between obesity and strategies that prevent undesired pregnancies constitutes a significant public health and economic concern. Evidence from recent epidemiological studies and our preliminary data (sub-therapeutic levels of steroid hormones due to drug clearance and half-life) suggest that obesity reduces oral contraceptive efficacy. Further studies are necessary to investigate whether these obesity related changes can be resolved. Such an understanding is critical to finding a contraceptive strategy with better efficacy for these women. The overall goal of this grant is to test several intervention strategies in order to reverse obesity-related pharmacokinetic differences in an effort to improve contraceptive efficacy for these women. The main hypothesis for this proposal is that increased Body Mass Index (BMI) alters oral contraceptive metabolism in a manner which results in inadequate hypothalamic-pituitary-ovarian axis suppression during oral contraceptive use in obese women. Reproductive-aged, ovulatory women of obese (BMI >30 kg/m2), will be placed on oral contraceptives for 2 months, then randomized into two intervention arms for an additional 2 months. At several key time points, synthetic steroid pharmacokinetics, gonadotropins (LH, FSH) and ovarian hormone levels (estradiol, progesterone), ovarian follicular activity by ultrasound monitoring, and cervical mucus testing will be monitored.

避孕失败是美国意外怀孕的主要原因。其肥胖率 在流行病的比例，肥胖和预防意外怀孕的策略之间的任何联系， 构成了重大的公共卫生和经济问题。最近流行病学研究的证据 以及我们的初步数据（由于药物清除率和半衰期导致的类固醇激素亚治疗水平） 表明肥胖会降低口服避孕药的效果。需要进一步研究 这些与肥胖相关的变化是否可以解决。这样的理解对于找到一个 为这些妇女提供更有效的避孕策略。 这项拨款的总体目标是测试几种干预策略，以扭转肥胖相关的 药代动力学差异，以提高这些妇女的避孕效果。主要 这一建议的假设是，身体质量指数（BMI）的增加改变了口服避孕药的代谢， 口服避孕药期间导致下丘脑-垂体-卵巢轴抑制不足的方式 用于肥胖妇女。 生育年龄、排卵期肥胖女性（BMI >30 kg/m2），将接受口服避孕药2 个月，然后随机分为两个干预组，再持续2个月。在几个关键时间点， 合成类固醇药代动力学、促性腺激素（LH，FSH）和卵巢激素水平（雌二醇， 孕激素）、通过超声监测的卵巢卵泡活性和宫颈粘液检测将被监测。