Estrogens, the menopause, and osteoporosis.

There is a persuasive rationale from the use of hormone replacement therapy (HRT) at the time of the menopause, but there are a number of factors which limit its widespread application for osteoporosis. These relate partly to the long-term efficacy of HRT when given for a finite duration at the time of the menopause, and long-term prospective studies are warranted to address this issue. In addition, there are problems in the acceptability of, and long-term compliance with, many HRT regimens. A further difficulty relates to the logic of targeting women at risk from osteoporosis at the time of the menopause when the benefits and risks of HRT are largely extraskeletal. There may be a case for targeting HRT much later in life provided that HRT regimens can be made acceptable to such patients. Finally, the importance of the menopause to the problems of osteoporosis has been overemphasized, and other factors are important in determining the geographic variation in hip fracture risk as well as the increase in age- and gender-specific incidence that has occurred in many countries. The causes from this are unknown, but are clearly not related to gonadal status, because these phenomena are observed both in men and in women. A plausible hypothesis is the differences in physical activity between communities and the decrease in physical activity within communities. It will be important to determine the etiology of these phenomena so that logical preventive strategies can be developed.