Normal women have menopause (ovarian failure) at a mean age of 51 years. The resulting lack of estrogen is associated with rapid bone loss due to increased bone resorption and often consequent osteoporosis. (See "Pathogenesis of osteoporosis".) Many women also experience menopausal symptoms, including hot flashes, vaginal dryness, and urinary symptoms, all of which are relieved most effectively by estrogen therapy with or without a progestin.
For women with menopausal symptoms, estrogen is often given short-term (six months to five years), with the goal of eventual tapering and discontinuation (unless there is a compelling reason to continue long-term). (See "Menopausal hot flashes".)
Prior to the publication of the Women's Health Initiative, long-term (more than five years) estrogen and combined estrogen-progestin therapy were routinely prescribed for osteoporosis and coronary heart disease (CHD) based upon observational data demonstrating a protective antiresorptive effect of estrogen on bone and a positive effect on the heart.
However, currently available data from clinical trials do not confirm that estrogen prevents or delays cardiovascular disease. To the contrary, the Women's Health Initiative (WHI) and other trials suggest that combined estrogen-progestin is not cardioprotective and may slightly increase risk when used for either primary or secondary prevention of CHD. Moreover, combined therapy increases the risk of stroke, venous thromboembolism, and breast cancer , while unopposed estrogen therapy may increase stroke and venous thromboembolism, but not CHD or breast cancer risk. Of note, follow-up analyses suggest that older, but not younger postmenopausal women have excess CHD risk. (See "Postmenopausal hormone therapy and cardiovascular risk" and "Postmenopausal hormone therapy and the risk of breast cancer".)
In light of the WHI data and the efficacy of other antiresorptive drugs, including bisphosphonates and raloxifene, estrogen-progestin therapy should no longer be used solely for the prevention or treatment of osteoporosis. Exceptions include women with persistent menopausal symptoms and those who cannot tolerate the other drugs. (See "Overview of the management of osteoporosis in postmenopausal women".)