Estradiol-Receptor Blockade in Older Men and Women
- Conditions
- Normal Healthy Volunteers
- Interventions
- Registration Number
- NCT02271282
- Lead Sponsor
- Mayo Clinic
- Brief Summary
Repletion of testosterone (Te) in older men drives GH secretion after its aromatization to estradiol (E2), which acts via the estrogen receptor (ER). Conversely, we postulate that estrogen deprivation in postmenopausal women attenuates growth hormone (GH) secretion and insulin-like growth factor-1 (IGF-I) production, thus favoring development of metabolic syndrome in men treated with toremifene, a new estrogen antagonist used adjunctively in prostatic cancer
- Detailed Description
Systemic concentrations of Te, E2, GH, IGF-I and insulin growth factor binding protein 3 (IGFBP-3) decline in healthy aging men and women. 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. The estrogen-receptor antagonist, tamoxifen, blocks this effect of Te, suggesting involvement of E2 in GH's stimulation at least in young men. E2 alone stimulates GH secretion in young and older women. Because Te is converted to E2 by aromatization in the body, we postulate that E2 is the active moiety in both men and women. Moreover, we hypothesize that the decline of E2 in older men and women contributes to the fall in GH output. These basic concepts will be tested here.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Oral Placebo/Oral Toremifene GHRH/Ghrelin combined Injection Oral placebo will be given once on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral toremifene on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. Oral Toremifene/Oral Placebo GHRH/Ghrelin combined Injection Oral toremifene will be given once on Day 1 and continue daily x10 days. A single combined IV injection of growth hormone releasing hormone (GHRH)/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral placebo on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. Oral Placebo/Oral Toremifene Placebo Oral placebo will be given once on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral toremifene on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. Oral Toremifene/Oral Placebo Placebo Oral toremifene will be given once on Day 1 and continue daily x10 days. A single combined IV injection of growth hormone releasing hormone (GHRH)/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral placebo on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. Oral Toremifene/Oral Placebo Toremifene Oral toremifene will be given once on Day 1 and continue daily x10 days. A single combined IV injection of growth hormone releasing hormone (GHRH)/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral placebo on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. Oral Placebo/Oral Toremifene Toremifene Oral placebo will be given once on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit. After at least 3 weeks, subjects will return to receive oral toremifene on Day 1 and continue daily x10 days. A single combined IV injection of GHRH/ghrelin (both doses 0.3mcg/kg) will be given on the overnight visit.
- Primary Outcome Measures
Name Time Method Summed mass of growth hormone over 10 hours Participants will be followed for an average of 2 months with growth hormone measurements occuring 10 days after initiating study medication administration. Subjects will be given toremifene/placebo on Day 1 to take for 10 days. For one night between Days 8-12, from date of randomization, subjects will undergo a 12-h overnight (2200-1000h) fasting, every 10-min blood sampling. The primary analytical outcome is the summed mass of growth hormone (ie. mean/min/max) secreted in pulses over the first 10h of overnight blood samples. Pulsatile growth hormone is relevant, since sex-steroid hormones and regulatory peptides uniquely control growth hormone secretory-burst mass
- Secondary Outcome Measures
Name Time Method Growth hormone responsiveness over last 2h Participants will be followed for an average of 2 months with growth hormone measurements occuring 10 days after initiating study medication administration Subjects will be given toremifene/placebo on Day 1 to take for 10 days. For one night between Days 8-12, from date of randomization, subjects will undergo a 12-h overnight (2200-1000h) fasting, every 10-min blood sampling. The secondary analytical outcome is growth hormone responsiveness over the last 2 hours to bolus GHRH/ghrelin stimulation (ie. mean/min/max).
Trial Locations
- Locations (1)
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States