Estrogen pills for menopause symptoms vary in blood clot risk

The type of estrogen taken as a pill to treat menopause symptoms could make a difference in the risk of clot formation.

A recent observational study compared the safety of estradiol and conjugated equine estrogen. Of the two, estradiol was associated with a lower risk of leg vein and lung clots.

Researchers found that women patients at Group Health Cooperative who were prescribed estradiol had fewer of these blood vessel clots than did those prescribed Premarin. Estradiol is a generic, bio-equivalent estrogen. Premarin, a patented drug, is a conjugated equine estrogen.

University of Washington and Group Health Research Institute conducted the study. The results will be published this week in JAMA Internal Medicine.

“Although oral estrogens are effective for managing menopause symptoms, not enough is known about the cardiovascular safety of different oral hormone therapy products relative to each other,” said first author Nicholas L. Smith, professor of epidemiology at the UW School of Public Health. Smith directs the Veterans Affairs Seattle Epidemiologic Research and Information Center at the VA Puget Sound Health Care System. He is also an affiliate investigator at Group Health Research Institute.

To further understand the differences in risk, researchers measured clotting factors in the blood of women who did not develop a clot. Compared with estradiol users, conjugated equine estrogen users had levels that made them more prone to form blood clots, the researchers found.

The researchers also investigated the risk of heart attack and stroke, and found:

The risk of heart attack was somewhat, but not significantly, higher in women using oral conjugated equine estrogens than in those using oral estradiol.

No difference in the risk of stroke.

“If our results are confirmed,” Smith added, “women seeking menopausal treatment and their providers would find this information helpful when selecting a drug.”

This project, part of the Heart and Vascular Health study, included 384 Group Health members, aged 30 to 79, who were taking oral estrogen for menopause symptoms from 2003 through 2009. Menopausal symptoms can include hot flashes, night sweats and vaginal dryness, burning, and irritation.

On Feb. 1, 2005, Group Health’s pharmacy formulary (list of medicines) switched its preferred oral estrogen from conjugated equine estrogens to estradiol. The Heart and Vascular Health study is a case-control study in which Group Health members who have experienced cardiovascular events, such as heart attack or stroke, are matched with members who have not.

Smith’s co-authors were Marc Blondona, visiting scholar from the University Hospitals of Geneva, Switzerland; Leiden University Medical Center investigators Astrid van Hylckama Vlieg and Frits R. Rosendaal,; and UW investigators Kerri L. Wiggins, Laura B. Harrington, James S. Floyd, Melody Hwang, Joshua C. Bis, Barbara McKnight, Kenneth M. Rice, Thomas Lumley, Susan R. Heckbert and Bruce M. Psaty. At Group Health Research Institute,,Psaty is a senior investigator and Heckbert is an affiliate investigator.

###

The Heart and Vascular Health study is supported by grants HL43201, HL60739, HL68986, HL734105, HL7474, HL85251, and HL95080 from the National Heart, Lung, and Blood Institute of the National Institutes of Health.