Men, bone and estrogen: unresolved issues.

Gonadal function has long been known to be important for skeletal health in men. Prepubertal hypogonadism is clearly associated with impairment in peak bone mass development and adult-onset hypogonadism with accelerated bone loss. Gonadal failure results in deficits in both androgen and estrogen action, but traditionally androgens were assumed to have the most important skeletal effect in men. Recently that model has been reconsidered as a variety of kinds of evidence have appeared to document a critical role for estrogen in bone physiology. As a result of this fresh perspective a host of interesting new dilemmas and hypotheses are being examined, including those related to the mechanisms of sex steroid action in bone, the origins of gender differences in skeletal morphology and physiology, and the role of estrogen in diagnostic and therapeutic strategies in men with metabolic bone disorders.