Dose-Response of Gonadal Steroids and Bone Turnover in Older Men
Condition: Healthy Volunteers
Study type: Interventional

Summary: 
      The purpose of this study is to determine the levels of testosterone and/or estradiol at
      which changes in bone turnover, body composition, strength, sexual function etc. begin to
      occur in older men. This information may help determine when to intervene with hormone
      replacement therapy in aging men.
    

Detailed description: 
      In this protocol, men age 60-75 will be randomized to one of 6 groups. Groups 1-5 will
      receive goserelin acetate (Zoladex) plus 0 (placebo gel), 1.25, 2.5, 5, or 10* g/day of
      testosterone gel (Androgel). Group 6 will receive placebos for both goserelin acetate and
      testosterone gel. (*Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the
      trial due to reports of possible increased risk of cardiovascular events with testosterone
      administration).

      Subjects will be blinded with respect to group assignment. Dietary calcium intake will be
      assessed by a research dietitian and adjustments made through diet or supplements so that
      calcium intake is between 1000 and 1200 mg/day.

      Subjects will be seen on the Clinical Research Center at 4 week intervals for 16 weeks (0, 4,
      8, 12, and 16 weeks). At each visit, compliance with Androgel will be assessed by reviewing a
      medication diary. A standardized series of questions will be posed to each subject to assess
      potential side effects of the study drugs. Subjects receiving Androgel' will be given a new 4
      week supply of medication (except at week 16). A fasting blood and second voided urine sample
      will be collected. After the blood and urine samples have been obtained, subjects will be
      given their goserelin injection. The blood and urine tests listed below as well as
      anthropometric measures, and questionnaires will be performed at each visit. Dual-energy
      x-ray absorptiometry (DXA), quantitate computed tomography (QCT) scans, and strength
      assessments will be performed at 0 and 16 weeks only. Subjects who discontinue participation
      at or after week 8 will be asked if they are willing to have an early discontinuation visit
      in which all procedures normally done at week 16 will be performed.

      The following measures will be assessed:

        -  Routine chemistries and prostate specific antigen, PSA (for safety assessment)

        -  Bone turnover using blood and urine tests

        -  Hormones

        -  Lipids

        -  Body composition

        -  Strength

        -  Sexual desire and erectile function

        -  Bone mineral density and bone microarchitecture
    

Intervention name(s): Testosterone; Goserelin acetate
Intervention type(s): Drug; Drug
Intervention description(s): Androgel placebo or 1.25, 2.5, 5. or 10* gms topically each day; 3.6 gms sc every 4 weeks
Other intervention name(s): Androgel; Zoladex
Intervention MeSH terms: Goserelin; Testosterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic
Keywords: Testosterone; Bone turnover; Aging; Body composition; Hypogonadism; Sexual function