Reproductive Hormonal Effects of Weight Loss in Women

女性减肥对生殖激素的影响

• 批准号: 6847895
• 负责人: Nanette F. Santoro
• 金额: $ 16.7万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6847895
• 关键词: clinical research; estradiol; female; follicle stimulating hormone; gonadotropin releasing factor; hormone regulation /control mechanism; human middle age (35-64); human subject; hypothalamic pituitary adrenal axis; leptin; luteinizing hormone; menopause; menstrual cycle; ovulation; progesterone; reproductive hormone; secretion; stomach /intestine bypass; tumor necrosis factor alpha; ultrasonography; weight loss; women' s health

DESCRIPTION (provided by applicant): More than half of all US adults are overweight or obese, and over 5% of US health expenditures are directed at medical costs associated with obesity. We have recently reported, in a cohort of 842 women aged 43-55, dramatic differences in reproductive hormone patterns in ovulatory overweight and obese women, compared to women with a body mass index less than 25 kg/m2, during the early stages of the menopausal transition. These changes include longer and more irregular cycles, and decreased LH, FSH, estradiol and luteal progesterone metabolite excretion in urine over the course of an entire menstrual cycle. These alterations in menstrual cycle hormones may represent chronic, weight related changes, and may play a role in the morbidity of obesity, We propose to test the hypothesis that weight loss in obese women will result in normalization of reproductive hormones and to determine potential mechanisms for this salutary effect. We propose to determine the acute and chronic effects of a large weight reduction (at least 25% reductions from mean starting weight) in 30 morbidly obese women aged 35-50 who are scheduled to undergo gastric bypass surgery on daily reproductive hormone patterns, folliculogenesis, central neural GnRH drive and adipokines. We will examine whole cycle reproductive hormone patterns; early follicular phase pulsatile LH secretory patterns; serial transvaginal ultrasounds for one cycle or up to 25 days; and leptin, adiponectin and TNF alpha serum levels before, and at two time points after, gastric bypass. Demonstration of the reversibility of obesity related changes in menstrual cyclicity would provide support for the conduct of a randomized, clinical trial, and the proposed detailed monitoring can be used to provide important clues to the mechanisms by which the acute and chronic reversal of obesity impacts upon female reproduction. Thus, this initial exploration, if positive, would provide the basis for a new line of investigation for the PI into the interactions between reproduction and metabolism.

描述（由申请人提供）：超过一半的美国成年人超重或肥胖，超过 5% 的美国医疗支出用于与肥胖相关的医疗费用。我们最近报道，在 842 名 43-55 岁女性的队列中，排卵超重和肥胖女性的生殖激素模式与体重指数低于 25 kg/m2 的女性相比，在排卵早期阶段存在显着差异。更年期过渡。这些变化包括周期更长、更不规则，以及整个月经周期中 LH、FSH、雌二醇和黄体孕酮代谢物在尿液中的排泄量减少。月经周期激素的这些变化可能代表慢性的、与体重相关的变化，并且可能在肥胖的发病中发挥作用。我们建议检验肥胖女性体重减轻将导致生殖激素正常化的假设，并确定潜在的机制这种有益的效果。我们建议确定 30 名 35-50 岁病态肥胖女性的体重大幅减轻（平均起始体重至少减少 25%）对日常生殖激素模式、卵泡发生、胃绕道手术的急性和慢性影响，这些女性计划接受胃绕道手术。中枢神经 GnRH 驱动和脂肪因子。我们将检查整个周期的生殖激素模式；早期卵泡期脉动性 LH 分泌模式；连续经阴道超声检查一个周期或长达 25 天；以及胃绕道术之前和之后两个时间点的瘦素、脂联素和 TNF α 血清水平。证明肥胖相关的月经周期变化的可逆性将为开展随机临床试验提供支持，并且拟议的详细监测可用于为肥胖的急性和慢性逆转影响的机制提供重要线索。女性生殖。因此，这一初步探索如果是积极的，将为 PI 生殖与代谢之间相互作用的新研究线提供基础。