Testosterone-Driven Growth-Hormone (GH) Secretion in Aging Men

Study Overview
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Brief Summary
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This study is being done to understand how testosterone, the major male sex hormone, controls the pituitary gland's secretion of growth hormone (GH). GH is an important metabolic hormone, which controls sugar; fat and protein use in the body and maintains muscle strength and bone calcium content. Both testosterone and GH decline in older men. The age-related fall in these hormones probably contributes to relative frailty, reduced quality of life, bone loss, muscle wasting and impaired sexual function.

Detailed Description
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Repletion of testosterone in older men drives pulsatile GH secretion via conjoint facilitation of feedforward by the primary secretagogues GHRH and GHRP and repression of feedback by the dominant inhibitor, somatostatin; and, in corollary, testosterone acts via aromatization to estradiol and/or reduction to 5 alpha-dihydrotestosterone

Official Title
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Mechanisms of Testosterone-Driven Growth-Hormone (GH) Secretion in Aging Men: Modulation of GHRH, GHRP and Somatostatin Action by Estrogenic Versus Androgenic Steroids

Conditions
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Aging

Intervention / Treatment
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* Drug: Placebo
* Drug: Testosterone
* Drug: Anastrazole
* Drug: Dutasteride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy men between the ages of 50 and 80; normal weight (within 30% of ideal body weight defined by New York Metropolitan Life tables); and normal hematocrit (greater than 38%); community dwelling; and voluntarily consenting Exclusion Criteria: recent use of psychotropic or neuroactive drugs (within five biological half-live); obesity (outside weight range above); anemia (hematocrit < 38%); drug or alcohol abuse, psychosis, depression, mania or severe anxiety; acute or chronic organ-system disease; endocrinopathy, other than primary thyroidal failure receiving replacement; nightshift work or recent transmeridian travel (exceeding 3 time zones within 7 days of admission); acute weight change (loss or gain of > 2 kg in 6 weeks); allergy to administered compounds; and unwillingness to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Double Placebo<br>(i.m. vehicle 0.5 mL weekly x three injections and oral placebo once daily x 21 days) | Drug: Placebo<br>* im and orally<br>|
| Other: Testosterone IM and oral placebo<br>IM injections weekly x three injections and oral placebo once daily x 21 days | Drug: Testosterone<br>* injections<br>|
| Other: Testosterone and Oral Anastrozole<br>IM injections weekly x 3 injections and oral daily x 21 days | Drug: Testosterone<br>* injections<br>Drug: Anastrazole<br>* orally x 21 days<br>|
| Other: Testosterone and Dutasteride<br>IM injections weekly x 3 injections and oral once daily x 21 days | Drug: Testosterone<br>* injections<br>Drug: Dutasteride<br>* orally x 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth Hormone concentration after injections | GH will be measured 4 different times mornings within 16-21 days following the first testosterone injection (day 1). | 24 days |