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Effects of Transdermal Testosterone on Bone and Muscle in Older Men With Low Bioavailable Testosterone Levels

^a Center on Aging, University of Connecticut Health Center, Farmington
^b Lowell P. Weicker General Clinical Research Center, University of Connecticut Health Center, Farmington
^c Braceland Center for Mental Health and Aging, Institute of Living/Hartford Hospital, Hartford, Connecticut

Anne M. Kenny, Center on Aging, MC-5215 University of Connecticut Health Center, Farmington, CT 06030-5215 E-mail: kenny{at}nso1.uchc.edu.

Decision Editor: John E. Morley, MB, BCh

Background. A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men. The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation.

Methods. Sixty-seven men (mean age 76 ± 4 years, range 65–87) with bioavailable testosterone levels below 4.44 nmol/l (lower limit for adult normal range) were randomized to receive transdermal testosterone (two 2.5-mg patches per day) or placebo patches for 1 year. All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex-hormone binding globulin [SHBG], estradiol, and estrone), bone mineral density (BMD; femoral neck, Ward's triangle, trochanter, lumbar spine, and total body), bone turnover markers, lower extremity muscle strength, percent body fat, lean body mass, hemoglobin, hematocrit, prostate symptoms, and prostate specific antigen (PSA) levels.

Results. Twenty-three men (34%) withdrew from the study; 44 men completed the trial. In these men, bioavailable testosterone levels increased from 3.2 ± 1.2 nmol/l (SD) to 5.6 ± 3.5 nmol/l (p < .002) at 12 months in the testosterone group, whereas no change occurred in the control group. Although there was no change in estradiol levels in either group, estrone levels increased in the testosterone group (103 ± 26 pmol/l to 117 ± 33 pmol/l; p < .017). The testosterone group had a 0.3% gain in femoral neck BMD, whereas the control group lost 1.6% over 12 months (p = .015). No significant changes were seen in markers of bone turnover in either group. Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores. Strength increased 38% (p = .017) in the testosterone group and 27% in the control group (p = .06), with no statistical difference between the groups. In the testosterone group, body fat decreased from 26.3 ± 5.8% to 24.6 ± 6.5% (p = .001), and lean body mass increased from 56.2 ± 5.3 kg to 57.2 ± 5.1 kg (p = .001), whereas body mass did not change. Men receiving testosterone had an increase in PSA from 2.0 ± 1.4 µg/l to 2.6 ± 1.8 µg/l (p = .04), whereas men receiving placebo had an increase in PSA from 1.9 ± 1.0 µg/l to 2.2 ± 1.5 µg/l (p = .09). No significant differences between groups were seen in hemoglobin, hematocrit, symptoms or signs of benign prostate hyperplasia, or PSA levels.

Conclusions. Transdermal testosterone (5 mg/d) prevented bone loss at the femoral neck, decreased body fat, and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels. In addition, both testosterone and placebo groups demonstrated gains in lower extremity muscle strength, possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but resulted in no change in signs or symptoms of prostate hyperplasia.

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