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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1171.)
© 2004 American Heart Association, Inc.

Brief Reviews

Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials?

Kwang Kon Koh; Ichiro Sakuma

From the Division of Cardiology (K.K.K.), Gil Medical Center, Gachon Medical School, Incheon, Korea; and the Division of Cardiovascular Medicine (I.S.), Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Correspondence to Dr Kwang Kon Koh, Professor of Medicine, Director, Vascular Medicine and Atherosclerosis Unit, Division of Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-Dong, Namdong-Gu, Incheon, Korea 405-760. E-mail kwangk{at}ghil.com

Many observational studies and experimental and animal studies have demonstrated that estrogen replacement therapy (ERT) or hormone replacement therapy (HRT) (estrogen plus progestin) significantly reduces the risk of coronary heart disease. Nonetheless, recent randomized controlled trials demonstrated some trends toward an increased risk of cardiovascular events rather than a reduction of risk. Recently, both the HRT and ERT arms of the Women’s Health Initiative (WHI) study were terminated early because of an increased/no incidence of invasive breast cancer, increased incidence of stroke, and increased trend/no protective effects of cardiovascular disease. We discuss the controversial effects of HRT and ERT on cardiovascular system and provide a hypothesis that the failure of HRT and ERT in reducing the risk of cardiovascular events in postmenopausal women might be because of the stage of their atherosclerosis at the time of initiation of HRT or ERT.

Recent randomized controlled trials have caused many people to suggest that the inclusion of the progestin in the HRT portion of this study is responsible for the adverse cardiovascular outcomes observed. Discussion of this issue is the focus of this review article.

Key Words: progestin • estrogen • women • cardiovascular disease

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