Sullivan raises the issue of the contribution of nonestrogen-mediated mechanisms to cardioprotection among premenopausal women.
The WHI hormone trials1,2 do not refute the hypothesis that estrogen protects premenopausal women against coronary heart disease (CHD) because oral administration of conjugated estrogens with or without progestin is physiologically different from endogenous reproductive hormone delivery. Rather, the trials establish that exogenous estrogen with progestin does not prevent CHD and that unopposed conjugated estrogens do not prevent CHD, except possibly among younger postmenopausal women. Differences in CHD risk between men and women may, in fact, be attributable to testosterone,3 not estrogen; the change in slope of CHD risk at menopause4 is not universally accepted. We did not discuss testosterone or other putative nonestrogen mechanisms, since these were not the focus of our trial.
Hsia J, Manson JE, Johnson KC, Hendrix SL, Heckbert SR, Crawford S, Eaton CB, Kostis JB. Estrogen and Heart Disease: Alternatives to a Paradigm in Crisis—Reply. Arch Intern Med. 2006;166(19):2160. doi:10.1001/archinte.166.19.2160-b