Impact of Estradiol Addback on Somatostatin Rebound in Older Men
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- BioStatistical Analysis
研究概览
简要总结
Repletion of testosterone (T) in older men drives Growth Hormone secretion after its aromatization to estradiol (E2) by potentiating endogenous GH drive.
详细描述
Systemic concentrations of Te, E2, GH, Insulin-like Growth Factor-I and IGFBP-3 decline in healthy aging men. Relative sex-steroid deprivation accentuates GH and IGF-I depletion, since Te stimulates GH and IGF-I production in older men, hypogonadal males of all ages, and patients undergoing (genotypic female-to-male) gender reassignment. Tamoxifen blocks this effect of Te, suggesting involvement of E2 in GH's stimulation in men. E2 per se stimulates GH secretion in women. Because Te is converted to E2 by aromatization in the body, we postulate that E2 is the active moiety in men also. Moreover, we hypothesize that the decline of E2 in older men contributes to the fall in GH output. This has never been tested. From a clinical vantage, understanding the mechanistic basis of Te's drive of the somatotropic axis is especially relevant in boys with pubertal failure, adults with primary hypogonadism and men with aging-related hypoandrogenemia. In relation to aging in the male, testosterone and E2 bioavailabilities fall by 35-50% in the eighth compared with third decade of life. From a medical perspective, aging is accompanied by progressive osteopenia, sarcopenia and intra-abdominal obesity. These adverse outcomes are remediable by short-term replacement with Te and/or recombinant GH, thus linking GH/Te/E2 availability with key body-compositional features.
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
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 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
Degarelix/Te/placebo/ placebo
Degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
干预措施: Degarelix (Drug)
Degarelix/Te/placebo/ placebo
Degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
干预措施: Testosterone (Drug)
degarelix/Te/anastrozole/ placebo
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
干预措施: Degarelix (Drug)
degarelix/Te/anastrozole/ placebo
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
干预措施: Testosterone (Drug)
degarelix/Te/anastrozole/ placebo
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
干预措施: Anastrozole (Drug)
degarelix/Te/ anastrozole/E2 patch
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
干预措施: Degarelix (Drug)
degarelix/Te/ anastrozole/E2 patch
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
干预措施: Testosterone (Drug)
degarelix/Te/ anastrozole/E2 patch
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
干预措施: Anastrozole (Drug)
degarelix/Te/ anastrozole/E2 patch
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
干预措施: Estrogen patch (Drug)
degarelix/ placebo/placebo/no patch
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; placebo i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
干预措施: Degarelix (Drug)
结局指标
主要结局
BioStatistical Analysis
时间窗: Subjects will undergo 15-h overnight (2200 - 1300 h) fasting, 10-min blood sampling
The primary analytical outcome is the summed mass of GH secreted in pulses over the 15 h of overnight blood sampling. The outcome measure is relevant, since sex-steroid hormones and regulatory peptides uniquely control GH secretory-burst mass.
次要结局
未报告次要终点