The effects of progesterone and progestins on endometrial proliferation.

ABSTRACT

PIP: Use of micronized progesterone or a synthetic progestin has been shown to counter the proliferative effect of estrogen on the endometrium in pre- and postmenopausal women. The present study measured endometrial glandular proliferation rates in 99 pre- and 27 postmenopausal US women. Determinations were based on mitosis counts and both proliferating cell nuclear antigen and nuclear cyclin immunocytologic staining of endometrial tissue. In the untreated, normally cycling premenopausal subjects, glandular epithelial proliferation increased during the follicular phase and decreased during the luteal phase. Premenopausal women who received a synthetic progestin and untreated postmenopausal women who were not estrogen-primed showed minimal epithelial proliferation. The mean mitosis rate of proliferative phase glands was 12.3 compared with 1.6 and 0.01 after administration of the oral contraceptives norethindrone or norethynodrel, respectively. Among premenopausal women, the intensity of the stromal pseudodecidualization and inhibition of glandular development was greatest in those receiving monthly medroxyprogesterone acetate injections. The combination of progestin potency, dosage, and duration determined the mitoses, stroma, and glands that were present in the three groups of subjects. The methods used in this study may be of use in determining optimal dosages of exogenous progestins in women who are receiving hormone replacement therapy and the potential exists for predicting adverse endometrial responses to progestational therapy.