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％的美国健康支出针对与肥胖有关的医疗费用。最近，我们报道了在842名43-55岁的女性中，与体重指数小于25 kg/m2的女性相比，在绝经期早期阶段，排卵性超重和肥胖女性的生殖激素模式差异很大。这些变化包括更长，更不规则的周期，以及在整个月经周期的过程中尿液中尿液中尿液中的LH，FSH，雌二醇和黄体代谢物排泄。月经周期激素中的这些改变可能代表慢性，体重相关的变化，并可能在肥胖的发病率中发挥作用，我们建议检验以下假设：肥胖女性的体重减轻将导致生殖激素的归一化，并确定这种有力效应的潜在机制。我们建议在30名病态肥胖的35-50岁的肥胖女性中确定大量减轻体重的急性和慢性影响，这些肥胖女性计划在每日生殖激素模式，卵泡性激素发生，卵泡发生，中心神经GNRH和脂肪因子上进行胃旁路手术。我们将检查整个循环生殖激素模式；早期卵泡相脉动LH分泌模式；连续阴道超声检查一个周期或最多25天；和瘦素，脂联素和TNFα血清水平之前，在两个时间点之后，胃旁路。表明月经周期性中肥胖相关变化的可逆性将为进行随机，临床试验的进行提供支持，并且可以使用拟议的详细监测来为肥胖对女性繁殖的急性和慢性逆转的机制提供重要的线索。因此，如果积极的话，这种初始探索将为PI对生殖与代谢之间的相互作用的新研究提供基础。