Effects of Aromatase Inhibition on Bone Mineral Density and Bone Turnover in Older Men with Low Testosterone Levels

Context: Aging is associated with declining gonadal steroid production, low bone mineral density (BMD), and fragility fractures. The efficacy and safety of testosterone replacement in older men remains uncertain. Objective: The objective of the study was to assess the effects of aromatase inhibition on BMD in older men with low testosterone levels. Design and Setting: This was a 1-yr, double-blind, randomized, placebo-controlled trial that was conducted at a tertiary care academic center in Boston, MA. Participants: Participants included 69 men aged 60+ yr with borderline or low testosterone levels and hypogonadal symptoms. Intervention: Intervention included 1 mg anastrozole daily or placebo. Main Outcome Measures: Changes in gonadal steroid hormone levels, BMD, and bone turnover markers were measured. Results: Mean serum testosterone increased from 319 +/- 93 ng/dl at baseline to 524 +/- 139 ng/dl at month 3 (P < 0.0001) and declined slightly to 474 +/- 145 ng/dl by 1 yr. Estradiol levels decreased from 15 +/- 4 pg/ml at baseline to 12 +/- 4 pg/ml at month 3 and then remained stable (P < 0.0001). Posterior-anterior (PA) spine BMD decreased in the anastrozole group as compared with placebo (P = 0.0014). In the anastrozole group, PA spine BMD decreased from 1.121 +/- 0.141 g/cm(2) to 1.102 +/- 0.138 g/cm(2), whereas in the placebo group, PA spine BMD increased from 1.180 +/- 0.145 g/cm(2) to 1.189 +/- 0.146 g/cm(2). Qualitatively similar, but not statistically significant, changes occurred at the other sites. Bone turnover markers were not affected by anastrozole therapy. Conclusions: In older men, aromatase inhibition increases testosterone levels, decreases estradiol levels, and appears to decrease BMD. Aromatase inhibition does not improve skeletal health in aging men with low or low normal testosterone levels. (J Clin Endocrinol Metab 94: 4785-4792, 2009)