Public Release: 

Less blood clot risk is linked to estradiol than to Premarin pills

JAMA Internal Medicine publishes University of Washington -- Group Health study

Group Health Research Institute

SEATTLE--Women can choose among several types of estrogen pills, which are equally effective at relieving menopausal symptoms. But in an observational study of comparative safety, use of estradiol was associated with less risk of developing blood clots in leg veins (deep vein thrombosis) and clots in the lungs (pulmonary emboli) than was use of conjugated equine estrogens. According to a joint University of Washington (UW)-Group Health study in JAMA Internal Medicine, women patients of Group Heath who were prescribed a generic version of estradiol--a bio-equivalent estrogen--experienced fewer adverse vascular events than did those prescribed conjugated equine estrogens, a patented drug marketed as Premarin.

"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, PhD. He is a professor of epidemiology at the UW School of Public Health, the director of the Veterans Affairs (VA) Seattle Epidemiologic Research and Information Center (ERIC) at the VA Puget Sound Health Care System, and an affiliate investigator at Group Health Research Institute.

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

The researchers also investigated other cardiovascular events:

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

  • No difference was seen in the risk of stroke.

"If our results are confirmed," Dr. Smith added, "women seeking menopausal treatment and their providers would find this information helpful when selecting a drug." Menopausal symptoms include hot flashes, night sweats, and vaginal dryness, burning, and irritation.

This project, part of the Heart and Vascular Health study, involved 384 Group Health members, aged 30-79, who were taking oral estrogen for menopause symptoms from 2003 through 2009. On February 1, 2005, Group Health's formulary switched its preferred oral estrogen from conjugated equine estrogens to estradiol. The Heart and Vascular Health study is a case-control study, where Group Health members who develop cardiovascular events are matched with control members who do not.


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.

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

Cardiovascular Health Research Unit

The Cardiovascular Health Research Unit (CHRU) is a joint program of the University of Washington (UW) and Group Health. This research program seeks to further the development and application of knowledge related to the prevention of cardiovascular diseases. Through the collaborative efforts of organizations and researchers based in the Pacific Northwest, CHRU projects are developing innovative approaches to the evaluation of prevention and treatment efforts related to the cardiovascular health of the public. CHRU projects enhance bridges between medicine and public health that foster research on the epidemiology and prevention of cardiovascular diseases. The CHRU is a unit of the UW School of Medicine's Division of General Internal Medicine. In addition to Group Health, the CHRU maintains close ties with the Seattle-King County Health Department's Emergency Medical Service (EMS), the Seattle Medic One Program, and the UW Nutrition Obesity Research Center (NORC).

UW Medicine

The UW Medicine health system includes Harborview Medical Center, Northwest Hospital and Medical Center, Valley Medical Center, UW Medical Center, UW Neighborhood Clinics, UW Physicians, UW School of Medicine, and Airlift Northwest. UW Medicine also shares in the ownership and governance of Children's University Medical Group and Seattle Cancer Care Alliance, a partnership among UW Medicine, Fred Hutchinson Cancer Research Center, and Seattle Children's. UW Medicine has major academic and service affiliations with Seattle Children's, Fred Hutchinson Cancer Research Center, Veterans Affairs Puget Sound Health Care System in Seattle, and the VA Hospital in Boise, Idaho. The UW School of Medicine is the top public institution for biomedical research in funding received from the National Institutes of Health.

UW School of Public Health

The University of Washington School of Public Health is grounded in teaching, research, and service. For more than 40 years, our 10,000 graduates have gone on to transform communities and lead health organizations. Our faculty and students accomplish innovative research to meet the emerging challenges of the 21st century, such as environmental change, obesity and nutrition, health policy, health systems that work, and the social factors that affect our health. They promote the well-being of people locally, regionally, and globally.

Group Health Research Institute

Group Health Research Institute does practical research that helps people like you and your family stay healthy. The Institute is the research arm of Seattle-based Group Health Cooperative, a consumer-governed, nonprofit health care system. Founded in 1947, Group Health Cooperative coordinates health care and coverage. Group Health Research Institute changed its name from Group Health Center for Health Studies in 2009. Since 1983, the Institute has conducted nonproprietary public-interest research on preventing, diagnosing, and treating major health problems. Government and private research grants provide its main funding.

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