Evidence for the role of
estrogen in male bone metabolism has been confirmed by studies on a man with a genetic defect in the
estrogen receptor as well as men with
aromatase defects. All exhibited tall stature, delayed epiphysial closure, decreased bone density and increased bone turnover.
Estrogen is likely to affect bone turnover in men throughout life; therefore, we hypothesized that older men would show decreased
bone resorption in response to
estrogen therapy. To test our hypothesis, fourteen community-dwelling men with
osteopenia of the femoral neck were treated for 9 weeks with micronized
estradiol, 1 mg/d, a dose which is effective in postmenopausal women. Each subject served as his own control. Markers of
bone resorption, N-terminal
collagen crosslinks (NTX) and C-terminal
collagen crosslinks (CTX) and markers of bone formation,
osteocalcin (OC) and bone specific
alkaline phosphatase (BSAP) were measured every 3 weeks during a 9-week treatment period and 9 weeks post-treatment.
Sex hormones, gonadotrophins and calciotropic
hormones were measured at baseline, 9 weeks on treatment and 9 weeks post- treatment. After 9 weeks of treatment,
estradiol and
estrone levels increased significantly by greater than 6-fold and 15-fold, respectively. SHBG levels increased significantly by 17%.
Testosterone and free
testosterone levels decreased significantly by 27% and 34%, respectively. Markers of
bone resorption showed wide variation at baseline and while on treatment. There was no correlation between changes in bone markers and changes in
estrogen levels. During treatment, 11 patients showed a decrease of NTX or CTX, but three showed an increase. These three and one other subject had high initial levels of FSH and LH, suggesting some degree of primary gonadal failure, which decreased during
estrogen therapy. Thus, the change in NTX (and CTX) after 9 weeks of E2 treatment was correlated with initial FSH (r= -.66, p= .01) and LH (r= -.73, p= .003) values. In addition, the largest decrease in free
testosterone at 9 weeks was correlated with the higher values for NTX, CTX and BAP (r=-0.66, -0.68, -0.70 respectively; p< or =.01 for each of the markers). Treatment was generally well tolerated. Side effects of treatment were minimal, and included breast tenderness and decreased libido which reversed
after treatment. We conclude that it is feasible to give low dose
estrogen to healthy older men, but that the effects on bone turnover are not consistent. Changes in central feedback and in endogenous
sex hormone production may alter the response of bone turnover to exogenous
estrogen in this population.