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Exogenous Testosterone or Testosterone with Finasteride Increases Bone Mineral Density in Older Men with Low Serum Testosterone

Departments of Medicine (J.L.T.) and Biostatistics (K.A.E.), Emory University School of Medicine, Rollins School of Public Health, Atlanta, Georgia 30329; Department of Medicine (N.B.W.), University of Cincinnati College of Medicine, Cincinnati, Ohio 45267; and Department of Medicine (J.K.A., P.R.S., B.D.A., A.M.M., W.J.B.), Veterans Affairs-Puget Sound Health Care System (B.D.A. and A.M.M.), and Geriatric Research, Education and Clinical Center (A.M.M.), University of Washington School of Medicine, Seattle, Washington 98195

Address all correspondence and requests for reprints to: Dr. J. Lisa Tenover, Wesley Woods Health Center, 1841 Clifton Road Northeast, Atlanta, Georgia 30329-5102.

Older men, particularly those with low serum testosterone (T) levels, might benefit from T therapy to improve bone mineral density (BMD) and reduce fracture risk. Concerns exist, however, about the impact of T therapy on the prostate in older men. We hypothesized that the combination of T and finasteride (F), a 5-reductase inhibitor, might increase BMD in older men without adverse effects on the prostate. Seventy men aged 65 yr or older, with a serum T less than 12.1 nmol/liter on two occasions, were randomly assigned to receive one of three regimens for 36 months: T enanthate, 200 mg im every 2 wk with placebo pills daily (T-only); T enanthate, 200 mg every 2 wk with 5 mg F daily (T+F); or placebo injections and pills (placebo). Low BMD was not an inclusion criterion. We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry. Prostate-specific antigen (PSA) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate. Fifty men completed the 36-month protocol. By an intent-to-treat analysis including all men for as long as they contributed data, T therapy for 36 months increased BMD in these men at the lumbar spine [10.2 ± 1.4% (mean percentage increase from baseline ± SEM; T-only) and 9.3 ± 1.4% (T+F) vs. 1.3 ± 1.4% for placebo (P < 0.001)] and in the hip [2.7 ± 0.7% (T-only) and 2.2 ± 0.7% (T+F) vs. -0.2 ± 0.7% for placebo, (P 0.02)]. Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip. After 6 months of therapy, urinary deoxypyridinoline (a bone-resorption marker) decreased significantly compared with baseline in both the T-only and T+F groups (P < 0.001) but was not significantly reduced compared with the placebo group. Over 36 months, PSA increased significantly from baseline in the T-only group (P < 0.001). Prostate volume increased in all groups during the 36-month treatment period, but this increase was significantly less in the T+F group compared with both the T-only and placebo groups (P = 0.02). These results demonstrate that T therapy in older men with low serum T increases vertebral and hip BMD over 36 months, both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men. In addition, the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy. These findings have important implications for the prevention and treatment of osteoporosis in older men with low T levels.

This work was supported by National Institutes of Health Grant AG10975.

Abbreviations: BMD, Bone mineral density; BPH, benign prostatic hypertrophy; CV, coefficient of variation; DHT, dihydrotestosterone; E2, estradiol; F, finasteride; po, per os; PSA, prostate-specific antigen; T, testosterone; TE, T enanthate.

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