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

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, 0.625 mg/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, 10 mg/day; and in group C (n = 73), dydrogesterone, 20 mg/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.