Over the past century, the average lifespan of women has increased from 50 to over 80 years, but the age of the menopause has remained fixed at 51 years. This "change of life" is marked by a dramatic and permanent decrease in circulating levels of ovarian estrogens. Therefore, more women will live a greater proportion of their lives in a chronic hypoestrogenic state. Ovarian steroid hormones are pleiotropic and have multiple, diverse, and possibly opposing actions in different contexts. In light of recent reports of the possible health risks of hormone replacement therapy (HRT) on several different physiological systems, the question of whether estrogens are protective or risk factors must be carefully re-evaluated.