Dose-Response of Gonadal Steroids and Bone Turnover in Men

Conditions:Healthy Studies
Therapuetic Areas:Other
Age Range:60 - 75
Start Date:September 2004
End Date:November 1, 2017

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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. This information may help determine when to intervene with hormone replacement therapy
in aging men.

There are 3 arms to this protocol, each with 5 or 6 groups.

In Arm 1, 240 men age 20-50 will receive goserelin acetate (Zoladex) plus Androgel (or

In Arm 2, 200 men age 20-50 will receive goserelin acetate (Zoladex) plus Androgel (or
placebo) plus anastrazole (Arimidex). NOTE: ARM 2 IS CLOSED TO RECRUITMENT..

In Arm 3, 240 men age 60 to 75 will receive goserelin acetate (Zoladex) plus Androgel (or

Subjects will be screened on the MGH General Clinical Research Center (GCRC). After obtaining
informed consent for the screening procedures, subjects will undergo a complete history and
physical examination. If no exclusionary findings are noted during the history and physical
examination, blood will be drawn to measure hemoglobin, routine chemistries (including serum
calcium, liver function tests, and creatinine), and serum levels of PTH, 25-OH vitamin D,
TSH, T, and PSA.

For Arm 3, subjects who are successfully screened will be randomly assigned by a computer to
one of 6 groups. All subjects will receive a GnRH agonist goserelin acetate (Zoladex;
AstraZeneca, Wilmington, DE) 3.6 mg sc every 4 weeks for 16 weeks. Subjects in Group 1 will
receive goserelin acetate and placebo for Androgel. Subjects in Groups 2-5 will receive
varying doses of Androgel. Subjects in Group 6 will receive double placebo (e.g. placebo
Zoladex and placebo Androgel). 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 GCRC 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. DXA, CT 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 PSA (for safety assessment)

- Bone turnover using blood and urine tests

- Hormones

- Lipids

- Body composition

- Strength

- Symptoms of hypogonadism

- Bone mineral density and bone microarchitecture

Inclusion Criteria:

- Healthy men age 20 to 50 years or 60 to 75. NOTE: RECRUITMENT OF MEN AGE 20-50 IS

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-OH vitamin D < 15 ng/mL

- Serum PTH < 10 or > 65 pg/mL

- Serum TSH < 0.5 or > 5.0 U/L

- Serum calcium > 10.6 mg/dL

- Serum creatinine > 2 mg/dL

- Serum AST or ALT > 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 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
We found this trial at
185 Cambridge Street
Boston, Massachusetts 02114
Principal Investigator: JOEL S. FINKELSTEIN, MD
Phone: 617-726-6723
Boston, MA
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