Unanswered questions in hormonal replacement therapy.

This review addresses many of the unanswered questions existing relative to the use of exogenous estrogens and progestins in postmenopausal women (PMW). The literature in the field is reviewed and summarized, with a particular effort to identify key questions of major concern. The effect of selection bias on conclusions reached from retrospective studies involving hormone replacement therapy (HRT) has not been examined. Less is actually known about the effects of progestins than estrogens. Many of the endocrine changes that occur with aging remain poorly defined. Effects of estrogens and progestins on the breast and on breast cancer are unclear. Estrogens have recognized beneficial effects and progestins have detrimental effects on lipoprotein metabolism. Estrogens also have direct effects on the vasculature and may impact on cardiovascular risk in other ways. Although estrogens are the only agents known to eliminate hot flushes, the mechanism by which flushes arise is not known. Estrogens may have ameliorating effects on mood and behavior and may improve dementia, but research in this area has been limited to date. Lastly, the preferred estrogens and progestins, their dosages and routes of administration, remain to be more completely defined.