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Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1516-1521
Published online before print May 27, 2004, doi: 10.1161/01.ATV.0000133683.65877.bc
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1516.)
© 2004 American Heart Association, Inc.


Atherosclerosis and Lipoproteins

Effects of Conventional or Lower Doses of Hormone Replacement Therapy in Postmenopausal Women

Kwang Kon Koh; Mi-Seung Shin; Ichiro Sakuma; Jeong Yeal Ahn; Dong Kyu Jin; Hyung Sik Kim; Dae Sung Kim; Seung Hwan Han; Wook-Jin Chung; Eak Kyun Shin

From the Departments of Cardiology (K.K.K., M.-S.S., D.K.J., S.H.H., W.-J.C., E.K.S.), Clinical Pathology (J.Y.A.), and Cardiovascular Medicine (I.S.), Hokkaido University Graduate School of Medicine, Sapporo, Japan; and the Departments of Radiology (H.S.K.) and Preventive Medicine (Biostatistics) (D.S.K.), Gachon Medical School, Incheon, Korea.

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

Objective— The effects of hormone replacement therapy (HRT) can affect many aspects relevant to cardiovascular disease, including vasomotor function, inflammation, and hemostasis. Recent studies have demonstrated that current doses of HRT exert a mixture of both protective and adverse effects. In the current study, we compared the effects of lower doses of HRT (L-HRT) and conventional doses of HRT (C-HRT) on a variety of relevant cardiovascular parameters.

Methods and Results— This randomized, double-blind, crossover study included 57 women who received micronized progesterone 100 mg with either conjugated equine estrogen 0.625 mg (C-HRT) or 0.3 mg (L-HRT) daily for 2 months. L-HRT showed comparable effects to C-HRT on high-density lipoprotein cholesterol and triglyceride levels, but not on low-density lipoprotein cholesterol levels. C-HRT and L-HRT significantly improved the percent flow-mediated dilator response to hyperemia from baseline values (both P<0.001) by a similar degree (P=0.719). C-HRT significantly increased high-sensitivity C-reactive protein (hsCRP) levels from baseline values (P<0.001); however, L-HRT did not significantly change hsCRP (P=0.874). C-HRT and L-HRT significantly decreased antithrombin III from baseline values (P<0.001 and P=0.042, respectively). C-HRT significantly increased prothrombin fragment 1+2 (F1+2) from baseline values (P<0.001); however, L-HRT did not significantly change F1+2 (P=0.558). Of interest, the effects of C-HRT and L-HRT on hsCRP, antithrombin III, and F1+2 were significantly different (all P<0.001). C-HRT and L-HRT significantly reduced plasma PAI-1 antigen levels from baseline values (P=0.002 and P=0.038, respectively) to a similar degree (P=0.184).

Conclusions— Compared with C-HRT, L-HRT has comparable effects on lipoproteins, flow-mediated dilation, and PAI-1 antigen levels. However, L-HRT did not increase hsCRP or F1+2 levels, and it decreased antithrombin III less than C-HRT.

Fifty-seven women received micronized progesterone 100 mg with either conjugated equine estrogen 0.625 mg (C-HRT) or 0.3 mg (L-HRT) daily for 2 months. Compared with C-HRT, L-HRT has comparable effects on lipoproteins, flow-mediated dilation, and PAI-1 antigen levels. However, L-HRT did not increase hsCRP or F1+2 levels.


Key Words: hormone replacement therapy • lower doses • endothelial function • inflammation • hemostasis • menopause




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