Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels

Background. A large proportion of men over 65 years of age have bioavailabl e testosterone levels below the reference range of young adult men. The imp act of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigat ion. Methods. Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioava ilable testosterone levels below 4.44 nmol/l (Lower limit for adult normal range) were randomized to receive transdermal testosterone (two 2.5-mg patc hes per day) or placebo patches for 1 year. All men received 500 mg supplem ental calcium and 400 IU vitamin D. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex-hormone binding globulin [SHB G], estradiol, and estrone), bone mineral density (BMD; femoral neck, Ward' s triangle, trochanter, lumbar spine, and total body), bone turnover marker s, lower extremity muscle strength, percent body fat, lean body mass, hemog lobin, hematocrit, prostate symptoms, and prostate specific antigen (PSA) l evels. Results. Twenty-three men (34%) withdrew from the study; 44 men completed t he 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 t estosterone group, whereas no change occurred in the control group. Althoug h there was no change in estradiol levels in either group, estrone levels i ncreased 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, whe reas 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 bas eline scores. Strength increased 38% (p = .017) in the testosterone group a nd 27% in the control group (p = .06), with no statistical difference betwe en 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. M en receiving testosterone had an increase in PSA from 2.0 +/- 1.4 mug/l to 2.6 +/- 1.8 mug/l (p = .04), whereas men receiving placebo had an increase in PSA from 1.9 +/- 1.0 mug/l to 2.2 +/- 1.5 mug/l(p = .09). No significant differences between groups were seen in hemoglobin, hematocrit, symptoms o r signs of benign prostate hyperplasia, or PSA levels. Conclusions. Transdermal testosterone (5 mg/d) prevented bone loss at the f emoral neck, decreased body fat, and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels. In addi tion, both testosterone and placebo groups demonstrated gains in lower extr emity 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.