Menopausal complaints, oestrogens, and heart disease risk: an explanation for discrepant findings on the benefits of post-menopausal hormone therapy.

There is a large discrepancy between the findings of observational and experimental studies on the effects of post-menopausal hormone therapy (HT) and coronary heart disease risk. Observational studies, mainly comprising peri-menopausal women, report risk reductions up to 30-50%, whereas the experimental studies, comprising elderly women, do not show coronary protection. Suggested explanations are methodological differences, such as confounding or healthy user bias, incomplete capture of early events, the stage of atherosclerosis at the start of HT, formulation or dose of HT, or early susceptibility to thrombotic events. We propose that the presence of climacteric complaints determines the susceptibility to hormone replacement therapy. Climacteric complaints are the main indication for HT in the population, whereas in the clinical trials women with climacteric complaints were either explicitly excluded or comprised only a minority of the total randomized population. There is some, albeit circumstantial evidence to support this hypothesis. Women with climacteric complaints of sweating not only appear to have lower levels of serum oestradiol, but also lose more bone than women without climacteric complaints. Consequently, sweating episodes may indicate potential benefits from HT. It has also been reported that hot flushes during menopause correlate with a higher level of oxidative stress and an increased cardiovascular reactivity to stressful situations. We suggest epidemiological approaches to test our hypothesis.