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Comparison of the difference in histopathology and cell cycle kinetics among the postmenopausal endometrium treated with different progestins in sequential-combined hormone replacement therapy

Chang, Ting-Chen MD1; Chen, Ming MD1,2; Lien, Yih-Ron MD1; Chen, Reuy-Jien MD, PhD1; Chow, Song-Nan MD, PhD1


Objective To investigate the difference in histopathology and cell cycle kinetics in the menopausal endometrium treated with sequential-combined hormone replacement therapy (HRT) using different types and doses of progestins.

Design A randomized, double-blind, 1-year study was conducted. In a menopause clinic of a university hospital, 241 postmenopausal women using HRT were included for the study of histopathology and cell cycle analysis. Conjugated equine estrogens, 0.625mg/day, were administered for 25 days (days 1–25) of each month, and the following were also administered for 14 days (days 12–25): in group A (n = 102), medroxyprogesterone acetate (MPA), 5 mg/day; in group B (n = 66), MPA, 10mg/day; and in group C (n = 73), dydrogesterone, 20mg/day. Endometrial sampling was performed after at least 10 months of treatment. Fifty-two premenopausal women were also enrolled for the comparative studies (group Y). The S-G2-M fractions in the cell cycle were used as the marker of proliferation.

Results Most menopausal endometria were normal regardless of the regimens of HRT. Endometrial hyperplasia was only found in two cases (both in group A). The S-G2-M fractions of the endometrial cells in all three menopausal groups showed no statistically significant difference. It appeared that S-G2-M fractions increased from normal postmenopausal to normal premenopausal endometria to postmenopausal hyperplasia to premenopausal hyperplasia. The S-G2-M fractions of the normal menopausal endometrial cells were lower than those of the premenopausal controls either in normal or in hyperplastic categories.

Conclusions Our study showed that there is no difference between the effect of MPA and dydrogesterone used in sequential-combined HRT based on the cycle kinetics of the menopausal endometrium.

From the 1Department of Obstetrics and Gynecology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, and the 2Institute of Medical Genetics, University of Glasgow, United Kingdom.

Received April 8, 2002; revised and accepted September 11, 2002.

This work was supported in part by grant NSC 89-2314-B-002-159 from National Science Council, The Executive Yuan of Republic of China, Taipei, Taiwan, and Global Vista Medical Foundation.

Address correspondence to Song-Nan Chow, MD, PhD, Professor and Head, Department of Obstetrics and Gynaecology, National Taiwan University Hospital, 7, Chung-Shan South Road, 10016 Taipei, Taiwan. E-mail:

©2003The North American Menopause Society