Effects of Aromatase Inhibition Versus Testosterone in Older Men With Low Testosterone: Randomized-Controlled Trial.

Phase 2

Completed

Conditions: Sarcopenia
Osteoporosis
Hypogonadism
Diabetes
Depression

Interventions: Drug: Androgel (Testosterone Gel)
Drug: Anastrozole (Aromatase Inhibitor)
Drug: Placebo gel
Drug: Placebo tablet
Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU

Registration Number: NCT00104572

Lead Sponsor: National Institute on Aging (NIA)

Brief Summary: Background: Men≥65 years often produce lower levels of testosterone, meaning there is less testosterone circulating to the tissues of the body. This is associated with negative effects on muscle strength, bone density, sexual function, mood, and the ability to think to the best of one's ability. Testosterone replacement therapy often involves injections, patches, or gels that help to raise circulating testosterone levels, but these therapies often have side effects because they lead to imbalance of other hormones. Researchers have been studying the effectiveness of anastrozole, a drug that can lower estrogen levels while simultaneously increasing testosterone levels, as a treatment for the negative effects of decreased circulating testosterone levels that occur naturally with aging. Objectives: To evaluate whether anastrozole is as effective as testosterone gel in improving bone and muscle strength, hormone levels, and brain function in men over 65 years of age. Eligibility: Healthy men at least 65 years of age who have low levels of testosterone. Design: The study involves six study visits over a total of 12 months: screening, baseline, 6 weeks, 3 months, 6 months, and 12 months. All participants will receive calcium and vitamin D supplements to take daily, and will be randomized to one of three groups:Testosterone gel and placebo tablet, Anastrozole tablet and placebo gel, Placebo tablet and gel. Participants will have the following tests at each specified visit:Screening: Blood tests and rectal ultrasound to evaluate the prostate;Baseline: Blood and urine tests; growth hormone levels, muscle strength, bone density, and balance evaluation; imaging studies; cognitive testing; and questionnaires on quality of life, sexual function, depression, and urinary symptoms;Six weeks: Blood tests and dose adjustment of the gel or tablet;Three months: Blood and urine tests; growth hormone, muscle strength, bone density, and balance evaluation; and questionnaires on quality of life, sexual function, depression, and urinary symptoms;Six months: Blood and urine tests; muscle strength, bone density, and balance evaluation; cognitive testing; and questionnaires on quality of life, sexual function, depression, and urinary symptoms;Twelve months: Blood and urine tests; rectal ultrasound; muscle strength, bone density, and balance evaluation; imaging studies; cognitive testing; and questionnaires on quality of life, sexual function, depression, and urinary symptoms.

Detailed Description: Approximately 20% of men over the age of 70 have low testosterone levels. In some studies, testosterone replacement has resulted in improvement in bone mass, muscle strength, quality of life and memory function. In the body, testosterone is converted into estrogen. Hence, it is unclear whether these beneficial effects are due to testosterone or estrogen. Research has shown that inhibition of estrogen production in men results in an increase in testosterone levels.

In this study, patients will be assigned to one of three groups: one group will receive testosterone gel and a placebo tablet, one group will receive a 1mg Anastrozole tablet and a placebo gel, and one group will receive a placebo tablet and placebo gel. Each group will receive a daily dose of calcium with vitamin D. The study requires 6 visits over a 12-month period for testing and evaluation. Two of the 6 visits will require an overnight stay in the hospital so that an intravenous (IV) line can be placed in the arm to allow samples to be drawn throughout the night. Testing will include a cardiac stress test, a glucose tolerance test, bone and muscle tests, evaluation of memory function, etc. For the safety of the prostate, we will perform a prostate ultrasound at the start and end of the study and we will monitor urinary symptoms, prostate specific antigen (PSA) levels and the prostate exam throughout the study.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo gel	13 participants will receive a placebo tablet and placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
(Androgel) testosterone gel	Androgel (Testosterone Gel)	17 participants will receive testosterone gel (5 gm) plus placebo tablet daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
anastrozole (Aromatase inhibitor)	Anastrozole (Aromatase Inhibitor)	14 participants will receive anastrozole 1 mg tablet plus placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
anastrozole (Aromatase inhibitor)	Calcium Cardone 500mg with vitamin D 400 IU	14 participants will receive anastrozole 1 mg tablet plus placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
(Androgel) testosterone gel	Calcium Cardone 500mg with vitamin D 400 IU	17 participants will receive testosterone gel (5 gm) plus placebo tablet daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
placebo	Calcium Cardone 500mg with vitamin D 400 IU	13 participants will receive a placebo tablet and placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
(Androgel) testosterone gel	Placebo tablet	17 participants will receive testosterone gel (5 gm) plus placebo tablet daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
anastrozole (Aromatase inhibitor)	Placebo gel	14 participants will receive anastrozole 1 mg tablet plus placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'
placebo	Placebo tablet	13 participants will receive a placebo tablet and placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'

Primary Outcome Measures

Name	Time	Method
Effect of Testosterone Gel vs. Anastrozole on Bone Mineral Density	1 year	bone mineral density lumbar spine for all arms testosterone gel, anastrozole and placebo

Secondary Outcome Measures

Name	Time	Method
Effect of Testosterone Gel vs. Anastrozole on Prostate Volume/Prostate Specific Antigen Levels/Urinary Function	1 year	rectal ultrasound prostate volume for all groups testosterone gel, anastrozole and placebo. Absolute changes in prostate volume in all treatment arms, calculation time frame 1 year minus baseline point.
Effect of Testosterone Gel vs. Anastrozole on Pulsatile Growth Hormone Release	1 year	Overnight Growth hormone measures (total hormone secretion) for groups testosterone gel, anastrozole and placebo
Effect of Testosterone Gel vs. Anastrozole on Glucose Tolerance/Lipid Metabolism	1 year	Primary outcome HOMA-IR for all groups testosterone gel, anastrozole and placebo Insulin resistance measure by HOMA-IR is a score if a person is insulin resistance the score should be between minimum 0.7- maximum 2 or more. Absolute changes in HOMAIR in all treatment arms, calculation time frame 1 year minus baseline point.