Dose-Response of Gonadal Steroids and Bone Turnover in Older Men
Dose-Response of Gonadal Steroids and Bone Turnover in Older Men
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.
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
Inclusion Criteria:

 -  Healthy men age 60 to 75

 Exclusion Criteria:

 -  History of significant cardiac, renal, pulmonary, hepatic, benign prostatic
 hyperplasia, or malignant disease, current alcohol or illicit drug abuse, or major
 psychiatric disorders.

 -  Current diagnoses of disorders known to affect bone metabolism including
 hyperthyroidism, hyperparathyroidism, osteomalacia, or Paget's disease.

 -  Current use of medications known to affect bone metabolism including estrogens,
 androgens, anti-estrogens, bisphosphonates, calcitonin, fluoride, oral or inhaled
 glucocorticoids, suppressive doses of thyroxine, lithium, pharmacological doses of
 vitamin D (greater than 2000 IU/day), or anti-convulsants.

 -  Cognitive or intellectual impairment that precludes complete understanding of the
 study protocol.

 -  History of deep vein thrombosis, pulmonary embolism, or clotting disorders.

 -  Serum 25-hydroxyvitamin D < 15 ng/mL

 -  Serum parathyroid hormone (PTH) < 10 or > 65 pg/mL

 -  Serum thyroid stimulating hormone (TSH) < 0.5 or > 5.0 U/L

 -  Serum calcium > 10.6 mg/dL

 -  Serum creatinine > 2 mg/dL

 -  Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2x the
 upper limit of normal

 -  Serum bilirubin > 2 mg/dL

 -  Serum alkaline phosphatase > 150 U/L

 -  Plasma hemoglobin < 11 gm/dL

 -  Hematocrit > 50

 -  Fracture within the last 6 months.

 -  Serum testosterone level < 270 or > 1070 ng/dL

 -  Serum prostate specific antigen (PSA) level > 4 ug/L.

 -  International Prostate Symptom Score (IPSS) > 19

 -  Systolic blood pressure > 160 or diastolic blood pressure > 95

 -  Framingham risk score greater than or equal to 20

 -  Difficulty walking 2 blocks