The currently reported data concerning the large WHI randomized controlled trial compare the impact of continuous combined conjugated estrogens + medroxyprogesterone acetate vs placebo in postmenopausal women. These results appear largely pessimistic. After 5.2 years of hormone replacement, an excess of coronary heart disease, cerebrovascular disease, venous thromboembolism, breast cancer incidence and extension, mild cognitive impairment and dementia is recorded. By contrast, osteoporotic fracture risk and colorectal cancer are decreased during hormone replacement. Accordingly, this hormonal treatment can no longer be recommended on a long term basis, except after extensive risk-benefit balance evaluation. It should no longer be prescribed for prevention of chronic diseases. It remains indicated during 4-5 years for relief of vasomotor symptoms, genital atrophy and, potentially, for some aspects of quality of life. HRT should probably be prescribed in minimal-effective dosages; new regimens, routes of administration, new compounds and associations should be envisaged in order to avoid cardiovascular or breast problems. However these new approaches ask for thorough validation studies.