Does estrogen adequately protect postmenopausal women against osteoporosis: an iconoclastic perspective.


Orwoll ES, Nelson HD.




J Clin Endocrinol Metab


In sum, the skeletal benefits provided by hormone replacement therapy are important, and estrogen should be justifiably considered one of the fundamentals of menopausal management. However, its efficacy in the prevention of osteoporotic fractures should not be overstated. Low bone mass and fractures remain serious threats in older postmenopausal women, even in the presence of hormone replacement. With the recognition of that reality comes a variety of challenges to clinicians and investigators. Clinicians should use estrogen to its best advantage, though, at the same time, remain vigilant of its limitations. Older postmenopausal women who are, or who have been, taking estrogen should not be a priori considered adequately protected against fracture. The same careful clinical evaluation recommended for the protection of those at increased fracture risk, including bone mass measures, should be available to estrogen-taking women in the later postmenopausal period. Recognizing this need, the National Osteoporosis Foundation has recently recommended bone mineral density testing in older women, regardless of estrogen status, and HCFA reimbursement has become available for this indication. In the presence of low bone density, estrogen-taking women should be afforded appropriate levels of diagnostic and therapeutic attention, with the intent to further reduce fracture risk. Once estrogen therapy has been elected, patients and their clinicians should be aware that bone loss can still be expected in the later postmenopausal years. Periodic reevaluations of bone density and other risks for fracture (e.g. falls) may be appropriate. In the face of continued good health, those reevaluations can be infrequent, but women who have medical conditions associated with adverse skeletal effects should be followed more closely despite their estrogen therapy. If we are to build on the value of estrogen to improve our approach to osteoporosis, additional data are needed. When fracture risk has been considered in complex models that adjust for account other medical and lifestyle variables, a greater protective effect of estrogen has emerged (12), suggesting that there are factors whose actions attenuate those of estrogen. Prominent candidates include genetics, tobacco and alcohol use, medications, body composition, and propensity to fall. There are undoubtedly others yet unidentified. These should be further defined, and the basic mechanisms for interactions between them and estrogen should be examined. It would be clinically advantageous to use these factors to accurately identify not only the women who would benefit from estrogen replacement but also those who would not. Because estrogen has important beneficial effects, an essential research objective should be the development of therapeutic strategies that combine the advantages of estrogen with other modalities (pharmacological or otherwise), to maximally protect the many estrogen-taking women who may be considered at continued risk for fracture. To whit, the initial reports of combination therapy with bisphosphonates are encouraging (13, 14). Other important skeletal agents can be anticipated to interact with estrogen in as-of-yet unforeseen ways. On another front, it can be anticipated that selective estrogen receptor modulators will be subject to estrogen-like limitations when used for osteoporosis prevention/therapy, and their effects will be influenced by a similar, but distinct, array of covariates. Our vision of the role of hormone replacement in the reduction of osteoporotic fracture risk should be considerably sharpened. At one time, estrogen was the lone best hope for the avoidance of fracture, but no longer should we be satisfied with that imperfect solution. The development of much more efficient and effective methods for osteoporosis risk assessment, prevention, and treatment now provides a chance to surpass previous expectations.