Testosterone Use in Men and Its Effects on Bone Health. A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

CONTEXT: Androgen-deficient men are at increased risk of osteoporosis. The extent to which testosterone can prevent and treat osteoporosis in men remains unclear. OBJECTIVE AND DESIGN: We performed a systematic review and meta-analysis of randomized placebo-controlled trials in men to estimate the effect of testosterone use on bone health outcomes. DATA SOURCES: The review encompassed librarian-designed search strategies using MEDLINE (1966 to March 2005), EMBASE (1988 to March 2005), and Cochrane CENTRAL (inception to March 2005); a review of reference lists from included studies; and content expert files. DATA COLLECTION: Independently and in duplicate, we assessed the methodological quality of the eligible trials and collected data on bone mineral density and bone fractures at the longest point of complete follow-up. DATA SYNTHESIS: We included eight trials enrolling 365 patients. Two trials followed patients for more than 1 yr. Meta-analysis of these trials showed that, compared with placebo, im testosterone was associated with an 8% (95% confidence interval, 4%, 13%) gain in lumbar bone mineral density and transdermal testosterone had no significant impact. Testosterone use was associated with a nonsignificant 4% (95% confidence interval, -2%, 9%) gain in femoral neck bone mineral density with unexplained differences in results across trials (26% of these differences were not explained by chance alone). No trials measured or reported the effect of testosterone on fractures. CONCLUSIONS: Intramuscular testosterone moderately increased lumbar bone density in men; the results on femoral neck bone density are inconclusive. Without bone fracture data, the available trials offer weak and indirect inferences about the clinical efficacy of testosterone on osteoporosis prevention and treatment in men.