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

NCT00104572 | Completed Phase 2 Results

• 3 other identifiers: 999904338NCT0010457204-AG-N338
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypogonadism; Diabetes; Sarcopenia; Osteoporosis; Depression

Keywords

Estrogen; Glucose Tolerance; Bone Density; Quality-of-Life; Sarcopenia

Outcome Measures

Primary Outcomes (1)

• Effect of Testosterone Gel vs. Anastrozole on Bone Mineral Density

  bone mineral density lumbar spine for all arms testosterone gel, anastrozole and placebo

  1 year

Secondary Outcomes (3)

• Effect of Testosterone Gel vs. Anastrozole on Pulsatile Growth Hormone Release

  1 year

• Effect of Testosterone Gel vs. Anastrozole on Glucose Tolerance/Lipid Metabolism

  1 year

• Effect of Testosterone Gel vs. Anastrozole on Prostate Volume/Prostate Specific Antigen Levels/Urinary Function

  1 year

Study Arms (3)

(Androgel) testosterone gel

EXPERIMENTAL

17 participants will receive testosterone gel (5 gm) plus placebo tablet daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'

Drug: Androgel (Testosterone Gel); Drug: Placebo tablet; Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU

anastrozole (Aromatase inhibitor)

EXPERIMENTAL

14 participants will receive anastrozole 1 mg tablet plus placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'

Drug: Anastrozole (Aromatase Inhibitor); Drug: Placebo gel; Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU

placebo

PLACEBO COMPARATOR

13 participants will receive a placebo tablet and placebo gel daily for 12 months and 'Calcium Cardone 500mg with vitamin D 400 IU'

Drug: Placebo tablet; Drug: Placebo gel; Dietary Supplement: Calcium Cardone 500mg with vitamin D 400 IU

Interventions

Androgel (Testosterone Gel) DRUG

1 mg tablet for 12 months

(Androgel) testosterone gel

Anastrozole (Aromatase Inhibitor) DRUG

anastrozole (Aromatase inhibitor)

Placebo tablet DRUG

Daily for 12 months

(Androgel) testosterone gel; placebo

Placebo gel DRUG

Daily for 12 months

anastrozole (Aromatase inhibitor); placebo

Calcium Cardone 500mg with vitamin D 400 IU DIETARY_SUPPLEMENT

1 tablet three times a day

(Androgel) testosterone gel; anastrozole (Aromatase inhibitor); placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• History of Stroke
• History of Dementia
• History of Diabetes
• Blood pressure at rest of \> 155/90 mmHg. Elevated systolic or diastolic reading renders subject ineligible
• Chronic medical condition, i.e. congestive heart failure
• Arthritis, severe enough to prevent completion of the strength testing, history of joint replacement of knees or hip.
• Inability to walk 50 meters
• Known disease of the bone and/or taking medications to treat osteoporosis, i.e.
• Fosamax, Evista, Miacalcin
• History of Gastric surgery
• History of prostate cancer or any other cancers, including blood dyscrasias
• History of severe benign prostatic hyperplasia (causing urinary problems)
• History of heart attack or open-heart surgery within the past 6 months
• Use of steroids within the past 3 months, including prednisone and/or cortisone injections, and inhaled steroids. Topical steroid cream is acceptable.
• If you do not agree to refrain from taking the drugs Viagra, Cialis or Levitra for the duration of the study

Sponsors & Collaborators

• National Institute on Aging (NIA): lead

Study Sites (1)

National Institute of Aging, Clinical Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (4)

• Jeffcoate SL, Brooks RV, Lim NY, London DR, Prunty FT, Spathis GS. Androgen production in hypogonadal men. J Endocrinol. 1967 Apr;37(4):401-11. doi: 10.1677/joe.0.0370401. No abstract available.

  PMID: 4290227 BACKGROUND

• Wheeler MJ. The determination of bio-available testosterone. Ann Clin Biochem. 1995 Jul;32 ( Pt 4):345-57. doi: 10.1177/000456329503200401. No abstract available.

  PMID: 7486793 BACKGROUND

• Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991 Nov;73(5):1016-25. doi: 10.1210/jcem-73-5-1016.

  PMID: 1719016 BACKGROUND

• Dias JP, Melvin D, Shardell M, Ferrucci L, Chia CW, Gharib M, Egan JM, Basaria S. Effects of Transdermal Testosterone Gel or an Aromatase Inhibitor on Prostate Volume in Older Men. J Clin Endocrinol Metab. 2016 Apr;101(4):1865-71. doi: 10.1210/jc.2016-1111. Epub 2016 Mar 7.

  PMID: 26950683 DERIVED

MeSH Terms

Conditions

Hypogonadism; Diabetes Mellitus; Sarcopenia; Osteoporosis; Depression

Interventions

Testosterone; Anastrozole; Aromatase Inhibitors; Vitamin D

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Physiological Effects of Drugs; Secosteroids

Results Point of Contact

• Title: Josephine M. Egan,MD, clinical director NIA
• Organization: NIA

eganj@grc.nia.nih.gov

410-558-8414

Study Officials

• Josephine M Egan, M.D.

  National Institute on Aging (NIA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2005
• First Posted: March 2, 2005
• Study Start: March 1, 2004
• Primary Completion: December 1, 2013
• Study Completion: January 1, 2015
• Last Updated: November 6, 2018
• Results First Posted: March 9, 2016

Record last verified: 2016-03

Locations

US (1)