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 women. We therefore hypothesized that older men would show increased bone resorption 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 of anastrozole, an aromatase inhibitor. After 9 weeks of treatment, there were significant decreases in estradiol, estrone, and sex hormone-binding globulin levels by 29%, 73%, and 16%, respectively, and total testosterone increased significantly by 56%. Despite the limited decrease of estrogen and the increase in testosterone, C-telopeptide of type 1 collagen showed a progressive significant increase of 11%, 24%, and 33% (P for trend = 0.033) above baseline at 3, 6, and 9 weeks, respectively. N-telopeptide of type 1 collagen values were highly correlated with C-telopeptide of type 1 collagen, but the change in N-telopeptide of type 1 collagen was not statistically significant. Bone-specific alkaline phosphatase and N-terminal type I procollagen peptides showed significant decreases of 8% and 11% of baseline at 9 weeks. Osteocalcin decreased significantly by 30% at 18 weeks. We conclude that aromatase inhibition can reduce estrogen levels in older men, but this effect is limited, perhaps because of feedback stimulation of testosterone production, and that endogenous estrogen derived from aromatization of testosterone plays a role in bone metabolism of older men by limiting the rate of bone resorption.
Taxel
P
P
Division of Endocrinology and Metabolism, Center on Aging, University of Connecticut Health Center, Farmington, Connecticut 06030-1317, USA. taxel@nso.uchc.edu
Kennedy
D G
DG
Fall
P M
PM
Willard
A K
AK
Clive
J M
JM
Raisz
L G
LG
D000368:Aged; D000077384:Anastrozole; D047072:Aromatase Inhibitors; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D016723:Bone Remodeling / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D015415:Biomarkers; D004791:Enzyme Inhibitors; D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D008055:Lipids; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole