Sex-related mechanisms have been proposed to explain the differences between men and women in the development of atherosclerotic disease, but none is supported by conclusive evidence. CAD rates of postmenopausal women are 2 to 3 times higher than for pre-menopausal women of the same age.1 However, the cardioprotective effect of estrogen has been called into question by the results of trials of hormone replacement therapy (HRT). The Heart and Estrogen/progestin Replacement Study (HERS) evaluated HRT in secondary CAD prevention and showed that HRT did not reduce the overall rate of CAD events.2 The Womens Health Initiative was a primary prevention trial whose estrogen-progestin HRT arm was stopped early because of a slight excess of cardiovascular events among the women receiving that hormonal treatment.3
The iron-depletion hypothesis proposes that with advancing age, iron stores rise to levels that exceed physiologic requirements, but that in premenopausal women, iron stores are maintained at low levels through regular iron loss in menstrual blood. Iron catalyzes the formation of reactive oxygen species, and excess stored iron has been implicated in atherogenesis.4,5 It has been suggested that increasing iron stores contribute to increasing CAD risk with advancing age, whereas iron depletion through menstrual blood loss is a factor in the lower CAD risk of younger women compared with men of the same age.
1. American Heart Association. Statistical fact sheets. Women and cardiovascular diseasesstatistics. Dallas, Tex: American Heart Association; 2005.
2. Hulley S, Grady D, Bush T. Randomized trial of et al. JAMA. 280:605-613.
3. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523-534.
4. Stadler N, Lindner RA, Davies MJ. Arterioscler Thromb Vasc Biol. 2004;24:949-954.
5. Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation. 1997;96:3300-3307.