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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