Impact of Endogenous Estrogen on Somatostatin Inhibition and Growth Hormone Rebound in Older Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- The summed mass of GH over 10 hours.
研究概览
简要总结
Endogenous estrogens maintain growth hormone (GH) secretion in postmenopausal women by potentiating endogenous GH-releasing hormone (GHRH) drive and restraining somatostatin inhibition of GH release.
详细描述
Systemic concentrations of testosterone (Te), estradiol (E2), GH, IGF-I and IGFBP-3 decline in healthy aging individuals (1-3). Sex-steroid deprivation accentuates GH and IGF-I depletion, since Te and E2 stimulate GH and IGF-I production in older adults, hypogonadal patients of all ages, and patients undergoing gender reassignment (1,2,4). Tamoxifen blocks the effect of Te, suggesting involvement of E2 in GH's stimulation in men (5). E2 also stimulates GH secretion in women, putatively via the nuclear estrogen receptor (ER-alpha) (1,2,6,7). Because Te, E2 and GH fall with menopause, and Te is converted to E2 by aromatization in the body (8-10), we postulate that diminished Te concentrations, Te→E2 concentrations and low E2 mediate low GH output in older women. What remains unknown is whether the low E2 levels in postmenopausal women retain GH-stimulating effects. To test this notion would require blocking: (i) aromatase-enzyme activity, which mediates E2 synthesis from Te, and/or (ii) estrogen receptor-alpha, which transduces most of E2's stimulation of the GH axis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
IM Placebo/Oral Placebo
IM placebo given once on Day 1; Oral placebo pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Placebo (Drug)
IM Placebo/Oral Placebo
IM placebo given once on Day 1; Oral placebo pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Somatostatin (Drug)
IM Placebo/PO Anastrozole
IM placebo given once on Day 1; Oral Anastrozole 2.0mg pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Anastrozole (Drug)
IM Placebo/PO Anastrozole
IM placebo given once on Day 1; Oral Anastrozole 2.0mg pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Placebo (Drug)
IM Placebo/PO Anastrozole
IM placebo given once on Day 1; Oral Anastrozole 2.0mg pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Somatostatin (Drug)
IM Fulvestrant/PO Placebo
IM Fulvestrant 250mg given once on Day 1; Oral Placebo pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Fulvestrant (Drug)
IM Fulvestrant/PO Placebo
IM Fulvestrant 250mg given once on Day 1; Oral Placebo pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Placebo (Drug)
IM Fulvestrant/PO Placebo
IM Fulvestrant 250mg given once on Day 1; Oral Placebo pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Somatostatin (Drug)
IM Fulvestrant/IM Anastrozole
IM Fulvestrant 250mg given once on Day 1; Oral Anastrozole pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Fulvestrant (Drug)
IM Fulvestrant/IM Anastrozole
IM Fulvestrant 250mg given once on Day 1; Oral Anastrozole pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Anastrozole (Drug)
IM Fulvestrant/IM Anastrozole
IM Fulvestrant 250mg given once on Day 1; Oral Anastrozole pills daily x14-18 days. Somatostatin 1mcg/kg/hr will be administered for 2 hours from 8-10AM on the overnight visit.
干预措施: Somatostatin (Drug)
结局指标
主要结局
The summed mass of GH over 10 hours.
时间窗: 14-18 days: From date of randomization to overnight visit
Subjects will be given placebo/fulvestrant and placebo/anastrozole on Day 1 to take for 14-18 days. For one night between Days 14-18, from date of randomization, subjects will undergo a 15-h overnight (2200-1300h) fasting, 10-min blood sampling. The primary analytical outcome is the summed mass of GH secreted in pulses over the first 10h of overnight blood samples. Pulsatile GH is relevant, since sex-steroid hormones and regulatory peptides uniquely control GH secretory-burst mass.
次要结局
- The summed mass of GH over a 2h Somatostatin infusion and 3h rebound window(14-18 days: From date of randomization to overnight visit)