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

Abstract

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