The Women's Health Initiative: New evidence, new ideas and a better understanding

The Women's Health Initiative (WHI) trial was a major contribution to the understanding of the risks and benefits of hormone therapy (HT) in postmenopausal women. Further analyses of the results of the WHI trial and a seminal review by Kuhl and Stevenson have put a new perspective on the benefits and risks of HT.1 It is suggested that (A) Breast cancer (i) Body mass and prior HT are important factors in determining the risk of breast cancer associated with HT. (ii) The increased risk of breast cancer with CEE+MPA in the WHI trial is an artefact due to the low incidence of breast cancer in the placebo group of women. (iii) The, so far, unexplained reduction in risk of breast cancer with CEE only in women age 50-59 could be due to the estrogen-induced reduction in insulin levels in the women who were overweight or obese, the majority of whom probably had the “metabolic syndrome” and hyperinsulinaemia. (B) Coronary Heart Disease (CHD) (i) CEE only in younger healthy postmenopausal women decreases the incidence of CHD but CEE+MPA in older women increases the incidence of CHD. (ii) Addition of MPA to CEE in postmenopausal women increases the risk of CHD possibly due to an MPAinduced upregulation of thrombin receptors in the coronary arteries. (iii) The effect of HT on the incidence of CHD is determined by age and by time since menopause on initiating HT. It is hypothesised that “HT in younger postmenopausal women prevents atherosclerosis and reduces the risk of cardiovascular disease BUT in older postmenopausal women increases the risk of thrombosis and inflammation and of cardiovascular disease in women with atherosclerotic plaques”. (C)Stroke and Total Mortality (i) The increased incidence of stroke in women over age 60 with both the CEE+MPA and CEE only arms of theWHI trial is the main reason for caution in the use of HT in older postmenopausal women (ii) The reduction in total mortality in women under 60 with both CEE+MPA and CEE only is an important new finding and requires further investigation. (iii) The significant reduction in total mortality provides reassurance, if any is needed, of the safety and benefits of HT in younger postmenopausal women O & G Forum Vol. 17 (4) 2007: pp. 105-110