Physiologic and pharmacologic effects of estrogen and progestins on bone

Estrogen deficiency has a primary role in the pathogenesis of osteoporosis, a major cause of morbidity and mortality in postmenopausal women. Estrogen therapy is associated with increased peak bone mass premenopausally and prevention of bone loss postmenopausally. The mechanisms by which estrogen exerts its effects on bone are not completely understood. Nonetheless, estrogen does affect calcium balance, and evidence suggests a direct mechanism via estrogen receptors on bone. The role of progestins in preventing bone loss is less well understood than that of estrogen. Studies in postmenopausal women and studies of add-back therapy in younger women have shown that norethindrone, but not medroxyprogesterone, treatment has a bone-sparing effect on cortical bone but not on trabecular bone. In addition, norethindrone, 5 or 10 mg daily, has effects on biochemical markers of bone turnover similar to those of estrogen, providing further evidence of a bone-sparing effect. The mechanisms for the effects of norethindrone on bone are unknown, although translocation of the estrogen receptor in an animal model and conversion in vivo to ethinyl estradiol have been postulated.