EFFECTS OF VARIOUS FORMS OF PROGESTIN ON THE ENDOMETRIUM OF THE ESTROGEN-PRIMED, OVARIECTOMIZED RAT

Progestin supplementation has been advocated in estrogen treatment for postmenopausal women to avoid proliferation of the endometrium. In this study we investigated the morphologic and biochemical effects of progestins on the endometrium of estrogen primed, ovariectomized rats. As the progestin derivatives, Allylestenol (AE), Norethisterone (NE), Danazol (DZ), Dydrogesterone (DG), Medroxyprogesterone acetate (MPA) and Cyproterone acetate (CPA), and as a anti-estrogen compound, Tamoxifen (TMX), were applied. To evaluate the effects of these different compounds on the endometrium, histologic studies and measurement of estrogen receptor concentrations were performed. When 19-nortestosterone groups, AE, DZ and NE, were orally administered to the conjugated equine estrogen (CE) treated, ovariectomized rats, the histologic pattern of the endometrium revealed rather a marked inhibition of hyperplasia induced by CE than a progestational response. Two of 3 of 17 alpha-hydroxyprogesterone groups, DG and MPA, provided slightly endometrial protection against the hyperplastic response, but another one, CPA, did not have any inhibitory effect on the estrogenic stimulation of the endometrium. TMX was not capable of suppressing the endometrial hyperplasia caused by CE administration. The average plasma concentrations of estradiol (E(2)) were 82.0+/-27.0 pg/ml (Mean+/-SD) after CE administration and there were no significant differences among these groups. Estrogen receptor concentrations of endometrium of progestins or antiestrogen added groups were not changed, when compared with the CE alone group. There was also no relationship between the estrogen receptor concentrations and the histologic findings in the endometrium. This discrepancy may be chiefly due to the low dose of the progestins as compared with the CE dose. In view of the morphologic findings for the endometrium, this study suggests that opposed estrogen treatment with 19-nortestosterone derivatives provides the most satisfactory endometrial protection against hyperplasia.