Sengwee Toh, ScD; Sonia Hernández-Díaz, MD, DrPH; Roger Logan, PhD; Jacques E. Rossouw, MD; Miguel A. Hernán, MD, DrPH
Acknowledgment: The authors thank the investigators and staff at the Women's Health Initiative Clinical Centers; the Women's Health Initiative Clinical Coordinating Center; and the National Heart, Lung, and Blood Institute Program Office. A complete list of Women's Health Initiative centers and investigators is available at www.whiscience.org/publications/WHI_investigators_longlist.pdf. They also thank Alvaro Alonso, MD, PhD (University of Minnesota), for analytic support and Garnet Anderson, PhD (Fred Hutchinson Cancer Research Center), for expert advice.
Grant Support: By the National Institutes of Health (grant R01 HL080644-01).
Potential Conflicts of Interest:Consultancies: S. Hernández-Díaz (AstraZeneca, Novartis, Pfizer). Grants received: S. Hernández-Díaz (Pfizer, Lilly, Novartis, Wyeth). Other disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-0301.
Reproducible Research Statement:Study protocol: Available at www.whiscience.org/about/design.php. Statistical code: Available from Dr. Toh (e-mail, email@example.com). Data set: The limited-access data set is available through application at the National Heart, Lung, and Blood Institute (https://biolincc.nhlbi.nih.gov/home/).
Corresponding Author: Sengwee Darren Toh, ScD, Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 133 Brookline Avenue, 6th Floor, Boston, MA 02215; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Toh: Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 133 Brookline Avenue, 6th Floor, Boston, MA 02215.
Drs. Hernández-Díaz, Logan, and Hernán: Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115.
Dr. Rossouw: Women's Health Initiative Branch, Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Rockledge 2 Building, Suite 10018, Bethesda, MD 20892.
Author Contributions: Conception and design: S. Toh, M.A. Hernán.
Analysis and interpretation of the data: S. Toh, S. Hernández-Díaz, R. Logan, J.E. Rossouw, M.A. Hernán.
Drafting of the article: S. Toh, M.A. Hernán.
Critical revision of the article for important intellectual content: S. Toh, S. Hernández-Díaz, J.E. Rossouw, M.A. Hernán.
Final approval of the article: S. Toh, S. Hernández-Díaz, J.E. Rossouw, M.A. Hernán.
Provision of study materials or patients: S. Toh.
Statistical expertise: S. Toh, R. Logan, M.A. Hernán.
Obtaining of funding: S. Hernández-Díaz, J.E. Rossouw, M.A. Hernán.
Administrative, technical, or logistic support: R. Logan, M.A. Hernán.
Collection and assembly of data: S. Toh, R. Logan.
Toh S, Hernández-Díaz S, Logan R, Rossouw JE, Hernán MA. Coronary Heart Disease in Postmenopausal Recipients of Estrogen Plus Progestin Therapy: Does the Increased Risk Ever Disappear?: A Randomized Trial. Ann Intern Med. 2010;152:211-217. doi: 10.7326/0003-4819-152-4-201002160-00005
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Published: Ann Intern Med. 2010;152(4):211-217.
Estrogen plus progestin therapy increases the risk for coronary heart disease (CHD) in postmenopausal women. However, this increased risk might be limited to the first years of use and to women who start therapy late in menopause.
To estimate the effect of continuous estrogen plus progestin therapy on CHD risk over time and stratified by years since menopause.
Women's Health Initiative randomized, double-blinded, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00000611)
40 U.S. clinical centers.
16 608 postmenopausal women with an intact uterus at baseline from 1993 to 1998.
Conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo.
Adherence-adjusted hazard ratios and CHD-free survival curves estimated through inverse probability weighting.
Compared with no use of hormone therapy, the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36 (95% CI, 1.55 to 3.62) for the first 2 years and 1.69 (CI, 0.98 to 2.89) for the first 8 years. For women within 10 years after menopause, the hazard ratios were 1.29 (CI, 0.52 to 3.18) for the first 2 years and 0.64 (CI, 0.21 to 1.99) for the first 8 years, and the CHD-free survival curves for continuous use and no use of estrogen plus progestin crossed at about 6 years (CI, 2 years to 10 years).
The analysis may not have fully adjusted for joint determinants of adherence and CHD risk. Sample sizes for some subgroup analyses were small.
No suggestion of a decreased risk for CHD was found within the first 2 years of estrogen plus progestin use, including in women who initiated therapy within 10 years after menopause. A possible cardioprotective effect in these women who initiated therapy closer to menopause became apparent only after 6 years of use.
National Heart, Lung, and Blood Institute.
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Cardiology, Coronary Heart Disease, Prevention/Screening.
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