Estrogen Effects on Bone in the Male Skeleton

Abstract

Estrogens in male are important in the control of linear growth, in the pubertal growth spurt, in epiphyseal maturation, and in the achievement of optimal peak bone mass. The failure to achieve peak bone mass may be a risk factor for the development of osteoporosis later in life. One approach to assess the relative roles of estrogen versus testosterone in the male skeleton has been to measure sex steroid levels in adult men, and to relate them in cross-sectional studies to bone mineral density (BMD) at various sites. Using this approach, it was found that in men over the age of 65 years, BMD was significantly positively associated with serum estradiol levels at all skeletal sites. In order to definitively dissect out estrogen versus testosterone effects on the adult male skeleton, Falahati-Nini et al. in 2000 studied 59 elderly men (mean age 68 years), in whom they eliminated endogenous testosterone and estrogen production, using a GnRH agonist (leuprolide acetate) and an aromatase inhibitor (letrozole). Following baseline studies in which markers of bone resorption and formation were measured, the men were randomized into one of four groups. Group A had both patches withdrawn, group B continued the estradiol patch but had the testosterone patch withdrawn, group C continued the testosterone patch but had the estradiol patch withdrawn, and group D continued both patches. After 3 weeks, the baseline studies were repeated. The estrogen had the dominant effect in preventing the increase in both urinary Dpd and NTx excretion that was observed in group A. These studies thus definitively established that estrogen was the major sex steroid regulating bone resorption in normal elderly men, although the data could not completely exclude a small effect of testosterone on bone resorption.