Micronized progesterone regulation of the endometrial glandular cycling pool

We sought to determine if micronized progesterone in estrogen-primed women has an effect on the available cycling pool of proliferating glandular cell s by studying 107 postmenopausal women who participated in a double-blind c yclical HRT trial. Each received 0.625 mg/day of conjugated equine estrogen (Premarin) orally for 6 weeks (cycle 1), followed by a baseline endometria l biopsy. These women were randomized to one of four doses (100 through 400 mg/day) of progesterone taken the last 10 days of each cycle or to estroge n only. Cyclical HRT (25-day cycles) was continued for three more cycles. E ndometrial biopsies were performed at the end of cycle 4 and 64 subjects de monstrated an adequate biopsy for immunohistochemical evaluation. The numbe r of proliferating gland cells was determined by an immunohistochemical sta in measuring positive MIB1 staining nuclei per thousand gland cells. The nu mber of proliferating endometrial gland cells in the cycling pool of women receiving 300- and 400-mg daily doses of progesterone was low (mean 4.9 and 1.7, respectively) when compared with women receiving 100 mg progesterone (mean 27.0) or to unopposed estrogen (mean 30.3). Late secretory endometriu m from 19 premenopausal women had a mean of 0.6. In the progesterone-treate d subjects, biopsies showed that secretory maturation increased as the seru m progesterone and doses of progesterone increased. We conclude that micron ized progesterone given to estrogen-primed menopausal women results in a do se dependent decrease in endometrial gland proliferation. The use of an imm unohistochemical stain and the diagnosis of histologic secretory maturation are complementary techniques in determining the inhibition of glandular pr oliferation.