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American Journal of Epidemiology Advance Access originally published online on May 25, 2009
American Journal of Epidemiology 2009 170(1):12-23; doi:10.1093/aje/kwp115
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American Journal of Epidemiology © The Author 2009. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Benefits and Risks of Postmenopausal Hormone Therapy When It Is Initiated Soon After Menopause

Ross L. Prentice, JoAnn E. Manson, Robert D. Langer, Garnet L. Anderson, Mary Pettinger, Rebecca D. Jackson, Karen C. Johnson, Lewis H. Kuller, Dorothy S. Lane, Jean Wactawski-Wende, Robert Brzyski, Matthew Allison, Judith Ockene, Gloria Sarto and Jacques E. Rossouw

Correspondence to Dr. Ross L. Prentice, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P.O. Box 19024, Seattle, WA 98109-1024 (e-mail: rprentic{at}fhcrc.org).

Received for publication August 20, 2008. Accepted for publication December 3, 2008.

The authors further analyzed results from the Women's Health Initiative randomized trials (1993–2004) of conjugated equine estrogens, with or without medroxyprogesterone acetate, focusing on health benefits versus risks among women who initiated hormone therapy soon after menopause. Data from the Women's Health Initiative observational study (1993–2004) were included in some analyses for additional precision. Results are presented here for incident coronary heart disease, stroke, venous thromboembolism, breast cancer, colorectal cancer, endometrial cancer, or hip fracture; death from other causes; a summary global index; total cancer; and total mortality. Hazard ratios for breast cancer and total cancer were comparatively higher (P < 0.05) among women who initiated hormone therapy soon after menopause, for both regimens. Among these women, use of conjugated equine estrogens appeared to produce elevations in venous thromboembolism and stroke and a reduction in hip fracture. Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism, stroke, and hip fracture but also included evidence of longer-term elevations in breast cancer, total cancer, and the global index. These analyses provide little support for the hypothesis of favorable effects among women who initiate postmenopausal estrogen use soon after menopause, either for coronary heart disease or for health benefits versus risk indices considered.

clinical trial; cohort studies; estrogens; estrogen replacement therapy; hormone replacement therapy; medroxyprogesterone 17-acetate; postmenopause; progestins


Abbreviations: CEE, conjugated equine estrogens; CHD, coronary heart disease; MPA, medroxyprogesterone acetate; WHI, Women's Health Initiative


Editor's note: An invited commentary on this article appears on page 24.


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