Invited Commentary: Hormone therapy risks and benefits--The Women's Health Initiative findings and the postmenopausal estrogen timing hypothesis.

Worldwide evidence on menopausal hormone therapy shows that it does not reduce coronary heart disease (CHD) risk and that it increases the risks of breast cancer, stroke, and venous thromboembolism. These risks are not offset by reductions in hip fracture risk. Consequently, the Food and Drug Administration and other drug regulatory authorities agree that hormone therapy should be used chiefly for short-term relief of menopausal symptoms. Continuing speculation relates to the "postmenopausal estrogen timing" hypothesis, which proposes that hormone therapy initiated soon after menopause will prevent CHD while therapy started later will have a null or adverse effect. The detailed analyses of Women's Health Initiative data reviewed here specifically address the timing hypothesis. For hormone therapy initiated soon after menopause versus therapy started later, the findings demonstrate 1) similar null or adverse effects on CHD risk; 2) similar adverse effects on the risks of stroke and venous thrombosis; and 3) possibly greater adverse effects on breast cancer risk. Therefore, Women's Health Initiative data do not support the hypothesis of favorable effects in women starting hormone therapy soon after menopause. Hence, the overall trial findings, including net harm for combined estrogen-progestin and the lack of a net benefit for estrogen-only therapy, also apply to women initiating hormone therapy soon after menopause.