Testosterone and Growth Hormone for Bone Loss in Men

Study Overview
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Brief Summary
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Deficiency of testosterone, growth hormone, or both hormones can result in osteoporosis. If either hormone is replaced, the condition of the bones improves. The purpose of this study is to determine if dual hormone treatment for men deficient in testosterone and growth hormone improves bone structure more than testosterone treatment alone.

Detailed Description
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Replacement of testosterone or growth hormone in patients who are deficient improves osteoporosis associated with these deficiencies. In some tissues, such as muscle, the effects of testosterone and growth hormone are additive, but it is not known if the effects are additive in bone as well. This study will compare the effects of testosterone alone with testosterone plus growth hormone in improving bone structure in men with total pituitary hormone deficiency. Participants in this study will be men who have pituitary or hypothalamic disease and have deficiencies of all pituitary hormones, but who have not been treated with either testosterone or growth hormone. The men will be randomly assigned to receive either testosterone alone or testosterone plus growth hormone for two years. Testosterone in a gel form will be applied daily to the skin. Growth hormone will be self-administered by daily subcutaneous injection. Blood concentrations of both hormones will be monitored with blood tests every 3 months during the 2-year study. Doses of the hormones will be adjusted to keep blood concentrations of the hormones within the normal range. Changes in bone structure will be assessed noninvasively before treatment and after one year and two years of treatment by magnetic resonance microimaging (µMRI) and dual energy X-ray absorptiometry (DEXA).

Official Title
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Will Testosterone and Growth Hormone Improve Bone Structure?

Conditions
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Hypopituitarism, Hypogonadism, Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Testosterone plus somatropin
* Drug: testosterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented hypothalamic or pituitary hormone deficiency Testosterone deficiency, defined as total serum testosterone less than 250 ng/dL at two 8 AM readings Growth hormone deficiency, defined by either of the following: For subjects who have thyroxine and cortisol deficiencies, either a subnormal age-specific IGF-1 or a peak GH response to arginine-GHRH of less than 4.1 ng/mL For subjects who do not have thyroxine and cortisol deficiencies, either a subnormal age-specific IGF-1 or a peak GH response to arginine-GHRH of less than 4.1 ng/mL Duration of testosterone and growth hormone deficiencies of two years or more Replacement of cortisol and/or thyroxine deficiencies Able to give informed consent Exclusion Criteria: Current testosterone treatment or treatment during the two years prior to study entry Current growth hormone treatment or treatment during the three years prior to study entry Use of other prescription or over-the-counter androgens (androstenedione, DHEA), estrogens, or antiandrogens (spironolactone, ketoconazole) Diseases that could influence bone, such as hyperparathyroidism Medications that could influence bone, such as anticonvulsants or glucocorticoids (prednisone greater than 20 mg/day for longer than 2 weeks/year). Calcium and over-the-counter vitamin D supplements are allowed. Cancer that could limit life expectancy to fewer than 5 years Neuromuscular disease or history of stroke with residual neurological defect Severe or uncontrolled psychiatric illness or dementia Noncancerous enlargement of the prostate gland (American Urological Association symptom score greater than 21) Prostate cancer by history, prostate nodule on digital rectal exam (DRE), or prostate specific antigen (PSA) greater than 4 Current alcohol or drug dependence Heart failure (New York class III or IV) Unstable angina Myocardial infarction within 3 months of study entry Liver disease (ALT greater than 3 x normal) Renal disease (serum creatinine greater than 2.5 mg/dl) Diabetes mellitus (glycosolated hemoglobin greater than 8.0%) Hypertension (systolic BP greater than 160 or diastolic BP greater than 100 mm Hg) Hematocrit greater than 48% Weight greater than 300 pounds Poor quality scan at baseline even when repeated Untreated, severe, obstructive sleep apnea (Epworth sleepiness score greater than 10) Unable to undergo an MRI because of a cardiac pacemaker or ferrometallic objects in the body

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Testosterone transdermally 5 g a day and somatropin subcutaneously 2 µg/kg body weight a day | Drug: Testosterone plus somatropin<br>* AndoGel 5 grams transdermally a day for two years Somatropin 2 µg/kg body weight/day for two years<br>|
| Active Comparator: 2<br>AndroGel transdermally 5 g a day for two years | Drug: testosterone<br>* AndroGel transdermally 5 g a day for two years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | Increased bone volume fraction (the fraction of bone that is bone, as opposed to the fraction that is marrow), as determined by magnetic resonance of the distal tibia | baseline, one year, two years |