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

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

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.

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Drug: Placebo; Drug: Testosterone; Drug: Anastrazole; Drug: Dutasteride

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Double Placebo; (i.m. vehicle 0.5 mL weekly x three injections and oral placebo once daily x 21 days)	Drug: Placebo; im and orally
OTHER: Testosterone IM and oral placebo; IM injections weekly x three injections and oral placebo once daily x 21 days	Drug: Testosterone; injections
OTHER: Testosterone and Oral Anastrozole; IM injections weekly x 3 injections and oral daily x 21 days	Drug: Testosterone; injections; Drug: Anastrazole; orally x 21 days
OTHER: Testosterone and Dutasteride; IM injections weekly x 3 injections and oral once daily x 21 days	Drug: Testosterone; injections; Drug: Dutasteride; orally x 21 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ACTUAL): August 1, 2008

Study Registration Dates

• First Submitted: March 31, 2006
• First Submitted That Met QC Criteria: March 31, 2006
• First Posted (ESTIMATE): April 3, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): July 31, 2012
• Last Update Submitted That Met QC Criteria: July 27, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Androgens; 5-alpha Reductase Inhibitors; Testosterone; Anastrozole; Dutasteride
• Other Study ID Numbers: 319-03