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The Effects of Aromatase Inhibition and Testosterone Replacement on Sex Steroids, Pituitary Hormones, Markers of Bone Turnover, Muscle Strength, and Cognition in Older Men

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Aging (NIA) )
ClinicalTrials.gov Identifier:
NCT00104572
First received: March 1, 2005
Last updated: May 2, 2013
Last verified: February 2013
History of Changes
  Purpose

Background:

- Men older than 65 years of age 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.

Condition Intervention Phase
Hypogonadism
Diabetes
Sarcopenia
Osteoporosis
Cognition
 Drug: Androgel (Testosterone Gel)
Drug: Anastrozole (Aromatase Inhibitor)
Drug: Placebo tablet
Drug: Placebo gel
Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Effects of Aromatase Inhibition and Testosterone Replacement in Sex Steroids, Pituitary Hormones, Markers of Bone Turnover, Muscle Strength, and Cognition in Older Men

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Improvements in bone quality, muscle strength, cardiac function, cognition, sexual and overall well-being [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Urinary symptoms [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Glucose tolerance [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Blood lab values [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effect of testosterone gel vs. anastrozole on sexual function, plasma viscosity, carotid intima & exercise tolerance
  • Effect of testosterone gel vs. anastrozole on effect on pulsatile GH release, cognition. muscle mass. strength and quality of life

Estimated Enrollment: 75
Study Start Date: March 2004
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
25 participants will receive testosterone gel (5 gm) plus placebo tablet daily for 12 months
 Drug: Androgel (Testosterone Gel)
1 mg tablet for 12 months
Drug: Placebo tablet
Daily for 12 months
Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU
1 tablet three times a day
Experimental: 2
25 participants will receive anastrozole 1 mg tablet plus placebo gel daily for 12 months
 Drug: Anastrozole (Aromatase Inhibitor)
N/A
Drug: Placebo gel
Daily for 12 months
Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU
1 tablet three times a day
Placebo Comparator: 3
25 participants will receive a placebo tablet and placebo gel daily for 12 months
 Drug: Placebo tablet
Daily for 12 months
Drug: Placebo gel
Daily for 12 months
Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU
1 tablet three times a day

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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

  • INCLUSION CRITERIA:

    1. Men age 65 years or older
    2. Serum testosterone level less than or equal to 350 ng/dl
    3. Subject is able to complete an informed consent

EXCLUSION CRITERIA:

  1. History of Stroke
  2. History of Dementia
  3. History of Diabetes
  4. Blood pressure at rest of > 155/90 mmHg. Elevated systolic or diastolic reading renders subject ineligible
  5. Chronic medical condition, i.e. congestive heart failure
  6. Arthritis, severe enough to prevent completion of the strength testing, history of joint replacement of knees or hip.
  7. Inability to walk 50 meters

  8. Known disease of the bone and/or taking medications to treat osteoporosis, i.e.

    Fosamax, Evista, Miacalcin

  9. History of Gastric surgery
  10. History of prostate cancer or any other cancers, including blood dyscrasias
  11. History of severe BPH (causing urinary problems)
  12. History of heart attack or open-heart surgery within the past 6 months
  13. Use of steroids within the past 3 months, including prednisone and/or cortisone injections, and inhaled steroids. Topical steroid cream is acceptable.
  14. If you do not agree to refrain from taking the drugs Viagra, Cialis or Levitra for the duration of the study
  15. Use of anabolic steroids, i.e. testosterone, (or any analog of testosterone) DHEA, DHEAS or any growth promoters i.e. growth hormone itself or analogs of growth hormone
  16. Use of anti-androgen medications, i.e. Aldactone, Tagamet, Proscar, estrogens
  17. Use of Dilantin or Phenobarbital
  18. Alcohol intake > 30 grams (drink more than 2 beers per day OR more than 1 glass of wine or cocktail daily)
  19. Currently smokes any tobacco product
  20. Having started a new medication during the past three months which may interfere with the outcome measures of the study
  21. Polycythemia
  22. PSA > 4.0 ng/dl
  23. Hematocrit < 36
  24. Liver function tests greater than 2 times upper normal limits or abnormal electrolytes, calcium or PTH, at the discretion of the investigator
  25. Mini Mental Status Exam score less than or equal to 24
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00104572

Locations
United States, Maryland
National Institute of Aging, Clinical Research Unit
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
National Institute on Aging (NIA)
Investigators
Principal Investigator: Josephine M Egan, M.D. National Institute on Aging (NIA)
  More Information

Publications:

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute on Aging (NIA) )
ClinicalTrials.gov Identifier: NCT00104572     History of Changes
Other Study ID Numbers: 999904338, 04-AG-N338
Study First Received: March 1, 2005
Last Updated: May 2, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Estrogen
Glucose Tolerance
Bone Density
Quality-of-Life
Sarcopenia

Additional relevant MeSH terms:
Hypogonadism
Osteoporosis
Sarcopenia
Gonadal Disorders
Endocrine System Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Signs and Symptoms
 Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Anastrozole
Vitamin D
Vitamins
Aromatase Inhibitors
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on May 16, 2013