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STATE-OF-THE-ART PAPER

Hormone Replacement Therapy and the Cardiovascular System

Lessons Learned and Unanswered Questions

Pamela Ouyang, MB, BS, FACC^_*,_*, Erin D. Michos, MD^_* and Richard H. Karas, MD, PhD, FACC

^_* Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Molecular Cardiology Research Center and the Division of Cardiology, Tufts-New England Medical Center, Boston, Massachusetts

Manuscript received October 5, 2005; accepted October 21, 2005.

^_* Reprint requests and correspondence: Dr. Pamela Ouyang, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, A1 East, Baltimore, Maryland 21224 (Email: pouyang{at}jhmi.edu).

Cardiovascular disease is the leading cause of death among women in the U.S., exceeding breast cancer mortality in women of all ages. Women present with cardiovascular disease a decade after men, and this has been attributed to the protective effect of female ovarian sex hormones that is lost after menopause. Animal and observational studies have shown beneficial effects of hormone therapy when it is initiated early in the perimenopausal period or before the development of significant atherosclerosis. However, randomized, placebo-controlled trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events, with a concerning trend toward harm. This review outlines the lessons learned from the basic science, animal, observational, and randomized trials, and then summarizes yet-unanswered questions of hormone therapy and cardiovascular risk.

Abbreviations and Acronyms   CHD = coronary heart disease   CI = confidence interval   CRP = C-reactive protein   HDLC = high-density lipoprotein cholesterol   HT = hormone therapy   IMT = intima-medial thickness   LDLC = low-density lipoprotein cholesterol   MI = myocardial infarction   MPA = medroxyprogesterone acetate

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