Skip to main content
Article
Estrogen and oxidative stress: A novel mechanism that may increase the risk for cardiovascular disease in women
Steroids
  • Richard E. White, Philadelphia College of Osteopathic Medicine
  • Ross Gerrity
  • Scott A. Barman
  • Guichun Han
Document Type
Article
Publication Date
1-1-2010
Abstract

Although early studies demonstrated that exogenous estrogen lowered a woman's risk of cardiovascular disease, recent trials indicate that HRT actually increases the risk of coronary heart disease or stroke. However, there is no clear explanation for this discrepancy. Is estrogen a helpful or a harmful hormone in terms of cardiovascular function? This review discusses some recent findings that propose a novel mechanism which may shed significant light upon this controversy. We propose that nitric oxide synthase (NOS) expressed within the vascular wall is a target of estrogen action. Under normal conditions in younger women, the primary product of estrogen action is NO, which produces a number of beneficial effects on vascular biology. As a woman ages, however, there is evidence for loss of important molecules essential for NO production (e.g., tetrahydrobiopterin, l-arginine). As these molecules are depleted, NOS becomes increasingly "uncoupled" from NO production, and instead produces superoxide, a dangerous reactive oxygen species. We propose that a similar uncoupling and reversal of estrogen response occurs in diabetes. Therefore, we propose that estrogen is neither "good" nor "bad", but simply stimulates NOS activity. It is the biochemical environment around NOS that will determine whether estrogen produces a beneficial (NO) or deleterious (superoxide) product, and can account for this dual and opposite nature of estrogen pharmacology. Further, this molecular mechanism is consistent with recent analyses revealing that HRT produces salutary effects in younger women, but mainly increases the risk of cardiovascular dysfunction in older postmenopausal women.

Comments

This article was published in Steroids, Volume 75, Issue 11, Pages 788-793.

The published version is available at http://dx.doi.org/10.1016/j.steroids.2009.12.007.

Copyright © 2010 Elsevier.

Citation Information
Richard E. White, Ross Gerrity, Scott A. Barman and Guichun Han. "Estrogen and oxidative stress: A novel mechanism that may increase the risk for cardiovascular disease in women" Steroids Vol. 75 Iss. 11 (2010) p. 788 - 793
Available at: http://works.bepress.com/richard_white/29/