Post Reproductive Health

Publication of the preliminary findings from the combination (oestrogen and progestogen) hormone therapy (HT) arm of the Women's Health Initiative (WHI) on the heels of the Heart and Estrogen/progestin Replacement Study (HERS) sent the field of menopausal medicine into turmoil. It is now considered that oestrogen therapy (ET)/HT should be used only to treat the short-term climacteric conditions associated with menopause and that its use to treat conditions associated with long-term oestrogen deprivation (ie, cardiovascular disease, osteoporosis and delay of the onset of dementia and Alzheimer's disease) is no longer appropriate. As a result, there has been a dramatic decrease in the number of patients using ET/HT. With few new therapeutic options on the horizon to treat either the short or long-term consequences of oestrogen deprivation, it seems that progress in the treatment of the menopausal patient has taken a large step backwards. This review considers how the direction of research in the field of menopausal medicine has been shaped by the WHI and outlines what the future might hold.

The probability that a menopausal woman will develop coronary heart disease is 46%, and 20% for stroke. Recently, the hormone replacement therapy paradigm on the balance of benefits and harm has been affected by puzzling information from several major randomised clinical trials showing no cardiovascular benefit. While studies may have shortcomings, clinical interpretation is also influenced by the fact that we are on a steep learning curve in pharmacoepidemiology and pharmacogenetics. This points to the clinical relevance of new findings from clinical studies on biomarkers, and from in vitro and animal research models. The research priority has been to identify the mechanisms and markers of risk and this potentially represents a significant scientific advance. It can lead to the identification of women who will benefit from hormone replacement therapy by preventing coronary heart disease and also improve testing of hormones that do not trigger any pro-thrombotic activity. Despite the pessimistic findings of recent epidemiological studies, it is biologically and metabolically plausible that in the years to come different hormonal treatments and use of new biomarkers will lead to therapies being individually targeted to benefit the cardiovascular system.