Clinical review 144: Estrogen and the male skeleton

The Journal of Clinical Endocrinology and Metabolism
Sundeep KhoslaB L Riggs

Abstract

Because estrogen (E) and T are the major sex steroids in women and men, respectively, the traditional view had been that E primarily regulated bone turnover in women and T played the analogous role in men. The description of ER- deficient and aromatase-deficient males, however, initiated a major shift in our thinking on the relative roles of T and E in regulating the male skeleton, because these individuals all had unfused epiphyses, high bone turnover, and osteopenia. Similar, albeit less striking, findings were noted in mouse models with knock-out of either the ER-alpha or the aromatase genes. Although these human experiments of nature and mouse knock-out models clearly demonstrated an important role for E in the growth and maturation of the male skeleton, they did not define the role of E vs. T in regulating the adult male skeleton. The past several years have witnessed an accumulation of evidence from observational as well as direct interventional studies that now clearly indicates that E plays a major, and likely dominant, role in bone metabolism in men. These data also suggest that a threshold level of bioavailable (or non-SHBG bound) E is needed for skeletal E sufficiency in the male, and that with aging, an increasing p...Continue Reading

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