Estrogens, progestins, SERMs, and osteoporosis

Abstract

Loss of ovarian function among mature women increases bone remodeling by increasing the frequency with which remodeling sites are activated and also by enhancing the avidity of the osteoclast population. The consequence is loss of bone mass and deterioration in the architecture of the skeleton with a resulting reduction in skeletal strength. The ubiquitous occurrence of menopause and the bone loss that follows renders osteoporosis and its attendant fracture risk a major health problem for the female population. Estimates suggest that the average woman has about a 50 % chance of a fracture in her remaining years. Replacement estrogen reduces that risk by essentially reducing remodeling toward premenopausal levels. However, the use of estrogen intervention is complicated since estrogens have potent effects in many organ systems, not all of which are beneficial. Thus, estrogen therapy is currently not considered to be a first line treatment when used solely for prevention of osteoporosis. Estrogens and hormone therapy (estrogen plus a progestin to protect the uterus) remain important agents for treatment of menopausal symptoms, with the recommendation that the lowest effective dose be given and that treatment be given for the shortest time possible (until symptoms remain abated when treatment is discontinued). The recommendation is a consequence of the Women Health Initiative, a major study from the USA that evaluated multiple outcomes of hormone therapy in postmenopausal women. As long as estrogen is given skeletal protection is to be expected, but when estrogens are stopped rapid bone loss ensues. For those considered at high risk for osteoporosis other strategies must be sought. When estrogens are used for osteoporosis prevention, care must be taken to ensure adequate calcium and vitamin D, since the estrogen efficacy relies on nutrition and is impaired when calcium intake is low and vitamin D levels are suboptimal.