[Historical perspective of hormone replacement therapy]

Clinical manifestations of menopause are partly related to estrogen deficiency. Estrogen replacement was long believed to reverse not only climacteric symptoms but also other chronic conditions associated with menopause such as osteoporosis, cognitive disorders or cardiovascular risk. However, it rapidly became obvious that hormone replacement therapy (HRT) was also associated with an increased risk of breast cancer and venous thrombo-embolic events. Until the end of the 1990's, based on cohort studies, HRT was thought to prevent cardiovascular complications of atherosclerosis. Risk/benefit ratio was thus considered as in favor of HRT, explaining its very wide prescription, after specific contra-indications have been ruled out. In 1998, the publication of HERS, the first randomized controlled study evaluating the effects of HRT in secondary cardiovascular prevention, allowed the scientific community to be conscious of the fact that HRT, not only did not prevent cardiovascular risk but also, probably, aggravated it. In 2002, the premature interruption of WHI study, by confirming that this was also true for primary prevention, has profoundly altered the common beliefs about HRT. Indeed, if HRT was associated with an increased cardiovascular risk, the benefits/risks ratio became unfavorable. Since that time, less women are treated and some of them have stopped their HRT. Recent recommendations have been published about indications of HRT, mainly based on the presence of climacteric symptoms. The potential interest of transdermic route for administration of estrogens needs to be confirmed. The potential deleterious effect of progestins needs to be explored. The difficult story of HRT had, at least, the merit to show, one more time, that in medicine, scientific evidence is always better than beliefs.