Estrogens and bone health in men

It has generally been held that estrogen and testosterone are the major sex steroids regulating bone metabolism in women and men, respectively. Howeve r, the description of several "experiments of nature" led to a reconsiderat ion of this notion. Thus, a male carrying homozygous mutations in the ER-a gene and two males with homozygous mutations in the aromatase gene had oste openia, unfused epiphyses, and elevated indices of bone turnover. Though th ese findings indicated that estrogen plays a role in regulating the male sk eleton, they left unresolved the issue of whether estrogen acted on the mal e skeleton mainly to enhance bone mass acquisition during growth and matura tion, or whether it also acted to retard bone loss in aging individuals. To address this issue, several cross-sectional observational studies have rel ated bone mineral density (BMD) to sex steroids in elderly men, and found t hat estrogen correlated better than testosterone with BMD. In addition, rec ent longitudinal studies from our group indicate that bioavailable estrogen correlated better than testosterone both with the gain in BMD in young men and with loss of BMD in elderly men. These observational studies do not, h owever, prove causality, which requires direct interventional studies. Thus , we eliminated endogenous testosterone and estrogen production in 59 elder ly men (mean age 68 years), studied them first under conditions of physiolo gic testosterone and estrogen replacement, and then assessed the impact on bone turnover of withdrawing both testosterone and estrogen, withdrawing on ly testosterone, only estrogen, or continuing both. We found that estrogen played the major role in regulating bone resorption in these men, and that both estrogen and testosterone were important in maintaining bone formation . Collectively then, these findings indicate that estrogen plays a dominant role in regulating the male skeleton.