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Effects of long-term and reduced-dose hormone replacement therapy on endothelial function and intima-media thickness in postmenopausal women

Hashimoto, Masayoshi MD, PhD1; Miyao, Mariko MD, PhD2; Akishita, Masahiro MD, PhD3; Hosoi, Takayuki MD, PhD2; Toba, Kenji MD, PhD3; Kozaki, Koich MD, PhD2; Yoshizumi, Masao MD, PhD2; Ouchi, Yasuyoshi MD, PhD2


Objective Short-term estrogen therapy improves endothelial function in postmenopausal women. However, there are few reports on its long-term effects on endothelial function and carotid intima-media thickness. Further, we determined whether a reduced dosage of estrogen may maintain its beneficial effects.

Design Eighteen postmenopausal women (53.7±1.1 years) who had been diagnosed as having osteoporosis were enrolled. Among them, 11 women were prescribed oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg per day, and 7 women were prescribed an oral calcium supplement as the control group. Each patient decided whether she would take hormone replacement therapy or a calcium supplement. We performed ultrasound measurement of endothelial function of the brachial artery and carotid intima-media thickness. Examinations were scheduled to be performed pre-therapy and after 3, 6, 12, 18, 24, and 36 months of therapy.

Results After three years of therapy, 6 women in the hormone replacement therapy group agreed to take half the dose of oral conjugated estrogen. Improvement of flow-mediated dilatation was observed at 3 months and the improvement was preserved up to 36 months. A similar improvement was also observed while women were on hormone replacement therapy even at the reduced dosage. Intima-media thickness of the common carotid artery in the control group increased after 12 months, which was not observed in the hormone replacement therapy group.

Conclusions Our results indicate that even at half the dose of estrogen, hormone replacement therapy may improve endothelial function and prevent the progression of carotid intima-media thickening in postmenopausal women.

From the 1 Department of General Internal Medicine, Kobe University School of Medicine, Kobe, Japan, 2 Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, and 3 Department of Geriatric Medicine, Kyorin University School of Medicine, Tokyo, Japan.

Received June 4, 2001;

revised and accepted August 17, 2001.

Address correspondence to Yasuyoshi Ouchi, MD, PhD, Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7–3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan. E-mail:

©2002The North American Menopause Society