The effect of aromatase inhibition on sex steroids gonadotropins, and markers of bone turnover in older men

There is evidence that estrogen decreases bone turnover in men as well as w omen. We therefore hypothesized that older men would show increased bone re sorption in response to inhibition of the aromatase enzyme, which converts androgens to estrogen. Fifteen eugonadal men over 65 yr were treated for 9 weeks with 2.0 mg/day o f anastrozole, an aromatase inhibitor. After 9 weeks of treatment, there we re significant decreases in estradiol, estrone, and sex hormone-binding glo bulin levels by 29%, 73%, and 16%, respectively, and total testosterone inc reased significantly by 56%. Despite the limited decrease of estrogen and t he increase in testosterone, C-telopeptide of type 1 collagen showed a prog ressive significant increase of 11%, 24%, and 33% (P for trend = 0.033) abo ve baseline at 3, 6, and 9 weeks, respectively. N-telopeptide of type 1 col lagen values were highly correlated with C-telopeptide of type 1 collagen, but the change in N-telopeptide of type 1 collagen was not statistically si gnificant. Bone-specific alkaline phosphatase and N-terminal type I procoll agen peptides showed significant decreases of 8% and 11% of baseline at 9 w eeks. Osteocalcin decreased significantly by 30% at 18 weeks. We conclude that aromatase inhibition can reduce estrogen levels in older m en, but this effect is limited, perhaps because of feedback stimulation of testosterone production, and that endogenous estrogen derived from aromatiz ation of testosterone plays a role in bone metabolism of older men by limit ing the rate of bone resorption.