Reproductive Hormonal Alterations in Obesity, AIMS #1 & #2
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)
研究概览
简要总结
The purpose of this study is to determine why obese women have lower hormone levels and less fertility than women of normal body weight. The proposal will examine the reproductive system at the level of the brain and the ovary to define the changes that happen leading to lowered hormone production. Women will be studied throughout a menstrual cycle and given medications that will test how well their pituitary gland can make hormones that stimulate the ovary (luteinizing hormone (LH) and follicle stimulating hormone (FSH)). They will also be given a medication to abolish estrogen production in the body and their response to this medication will be assessed. Finally, the ovary's ability to produce progesterone after ovulation will be examined.
--Hypotheses:
- Obese women have reduced pituitary sensitivity to exogenous gonadotropin-releasing hormone (GnRH), but normal clearance of exogenous LH. (comparative study of obese compared to normal weight women)
- Obese women have abnormally increased sensitivity to estradiol negative feedback which will be reversed by an aromatase inhibitor. (comparative study of obese compared to normal weight women)
详细描述
AIM 1: test the hypothesis that reduced pituitary sensitivity to GnRH-induced LH and FSH secretion causes the relative hypogonadotropic hypogonadism of obesity AIM 2: test the hypothesis that the hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Aged 18-40 at study entry
- •BMI either 18-25 kg/m2 or ≥30 kg/m2
- •prolactin (PRL) and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
- •Baseline hemoglobin >11 gm/dl
- •History of regular menstrual cycles every 25-35 days if BMI 18-25 kg/m2
- •History of regular menstrual cycles every 25-40 days if BMI ≥30 kg/m2
排除标准
- •History of chronic disease affecting hormone production, metabolism or clearance
- •Use of medications that are known to alter or interact with reproductive hormones (e.g., thiazolidinediones, metformin)
- •Use of hormones within three months of enrollment
- •Excessive exercise (>4 hours per week)
- •Pregnancy, breast-feeding or current active attempts to conceive
研究组 & 干预措施
BMI ≥30 kg/m2
Group 2:
- BMI ≥30 kg/m2
- History of regular menstrual cycles every 25-40 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Cetrorelix (Drug)
BMI ≥30 kg/m2
Group 2:
- BMI ≥30 kg/m2
- History of regular menstrual cycles every 25-40 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Gonadorelin-GnRH (Drug)
BMI ≥30 kg/m2
Group 2:
- BMI ≥30 kg/m2
- History of regular menstrual cycles every 25-40 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Recombinant LH (Drug)
BMI ≥30 kg/m2
Group 2:
- BMI ≥30 kg/m2
- History of regular menstrual cycles every 25-40 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Letrozole (Drug)
BMI 18-25 kg/m2
- BMI 18-25 kg/m2
- History of regular menstrual cycles every 25-35 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Cetrorelix (Drug)
BMI 18-25 kg/m2
- BMI 18-25 kg/m2
- History of regular menstrual cycles every 25-35 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Gonadorelin-GnRH (Drug)
BMI 18-25 kg/m2
- BMI 18-25 kg/m2
- History of regular menstrual cycles every 25-35 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Recombinant LH (Drug)
BMI 18-25 kg/m2
- BMI 18-25 kg/m2
- History of regular menstrual cycles every 25-35 days
Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
干预措施: Letrozole (Drug)
结局指标
主要结局
Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)
时间窗: Measured hourly and averaged over the 12 hour study visit
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 2)
时间窗: Measured hourly and averaged over the 12 hour study visit
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Changes in Pregnanediol Glucuronide (PdG) (Aim 2)
时间窗: Averaged over the length of menstrual cycle
Pregnanediol glucuronide (PdG) was collected daily over the course of one menstrual cycle and averaged.
次要结局
- Changes in Follicle Stimulating Hormone (FSH) (Aim 1)(Measured hourly and averaged over the 12 hour study visit)
- Changes in Follicle Stimulating Hormone (FSH) (Aim 2)(Measured hourly and averaged over the 12 hour study visit)