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COX inhibitors may weaken protective qualities of estrogen hormone therapy

PHILADELPHIA -- Researchers from the University of Pennsylvania School of Medicine found in a database study of women heart patients that COX inhibitors such as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) may undermine any purported protection against heart disease in participants taking estrogen therapy. The results were described this week in PLoS Medicine.

Premenopausal women are less susceptible to heart attack and stroke than are males of the same age group, an advantage that is lost after menopause. However, why this happens physiologically is unclear. Despite the cardiovascular advantage of premenopausal women, it has been difficult to identify a cardioprotective effect of taking estrogen in postmenopausal women. The Penn research group recently found in mice that estrogen acts via COX-2dependent prostacyclin, a fat that has a role in limiting blood clotting. Estrogen in this animal model acts via prostacyclin to decrease clotting and oxidative stress in cells and to limit hardening of the arteries.

"We were prompted to perform these studies while exploring the mechanism by which NSAIDs confer a cardiovascular hazard, that is suppression of COX-2 derived prostacyclin" says lead author Garret FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at Penn.

Inhibition of COX-2 by NSAIDs prevents production of prostacyclin. However, as estrogen acts to increase production of prostacyclin, the researchers surmise that the possible positive effects of estrogen therapy on the cardiovascular system may be counteracted by the COX-inhibiting NSAIDs.

To ascertain whether the failure to detect a benefit from estrogen might be partly attributable to a pharmacological interaction between inhibitors of COX-2 and estrogen, the researchers examined the medical records of 1,673 women between 50 and 84 from the United Kingdoms General Practice Research Database who had heart attacks or wh
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
23-May-2007


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