Hormone therapy: evolving concepts

To review the medical literature published in 2002 regarding menopausal hormone therapy and its impact on clinical practice.

A literature search was performed using MEDLINE with the keywords of menopause, sex steroids, and hormone replacement therapy. Randomized clinical trials were reviewed. An evidence-based review is presented.

Menopausal hormone therapy has undergone radical change since the publication of the Women's Health Initiative randomized prospective trial of combined estrogen plus progestin therapy for disease prevention. After a mean of 5.2 years of follow-up, the E + P versus placebo trial of 16,608 women was stopped because the health risks of taking E + P exceeded the benefits. An increase in breast cancer risk, coupled with an adverse trend in overall risk-benefit ratio, reached the preset stopping boundaries. In addition, there was an increased risk of nonfatal myocardial infarction, stroke, and pulmonary embolism. The decreased risks seen for osteoporotic fracture and colorectal cancer were outweighed by the above risks. The FDA has required mandatory label changes for all hormone products based on these findings. The Women's Health Initiative found that treatment with estrogen plus progestin for up to 5 years is not beneficial overall. There is early harm for coronary heart disease, continuing harm for stroke and venous thromboembolism, and increasing harm for breast cancer. This risk-benefit profile is not consistent with a viable intervention for primary prevention of chronic diseases in postmenopausal women. Menopausal hormone therapy should be reserved for women with moderate to severe vasomotor symptoms.

In the past 20 years, menopause has become a household word, with much better understanding of its consequences. The growing numbers of menopausal women and clinical trials have coincided to draw increasing attention to the perimenopausal and menopausal years. Better studies of older therapies and the expanded number of new choices today, with more in development and evaluation, have complicated provider and patient choices but greatly improved the potential for effective intervention.