The Women's Health Initiative (WHI) has conducted two randomized, placebo-controlled clinical trials to evaluate the influence of menopausal hormone therapy on chronic disease risk. Estrogen plus progestin was evaluated in 16,608 postmenopausal women without prior hysterectomy during 5.6 years' intervention. In that setting, combined hormone therapy use significantly increased breast cancer incidence and interfered with breast cancer detection. The breast cancers were not limited to estrogen receptor positive, favorable prognosis cancers and were identified at more advanced stage. As a result, deaths from breast cancer were significantly increased by estrogen plus progestin use. While the absolute breast cancer risk for relatively short term (2-4 years) use of combined hormone therapy is small, on a population basis a therapy which nearly doubles deaths from breast cancer requires cautious use. Estrogen alone was evaluated in 10,739 postmenopausal women with prior hysterectomy during 7.1 years' intervention. There was an overall reduction of breast cancer incidence seen with estrogen alone use and a suggestion that the effect on risk was more pronounced in women initiating hormone therapy further from menopause. Nonetheless, women with prior hysterectomy can be assured that short duration estrogen alone use for climacteric symptom management is relatively safe. Neither estrogen plus progestin nor estrogen alone should be used for chronic disease risk reduction. The safety of duration of use on chronic disease risk longer than in the WHI clinical trials is not defined.