Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes.

Authors: Moyer DL, de Lignieres B, Driguez P, Pez JP.

Publication Year: 1993

Citation: Fertil Steril 1993;59(5):992-7.

It is often presumed that progesterone levels must be high enough to induce endometrial bleeding by withdrawal in order to convey protection during estrogen replacement therapy. In this expanded observational study, the authors sought to determine the influence of withdrawal bleedings, secretory transformation, and reduction of mitosis on the prevention of endometrial hyperplasia during long-term estrogen-replacement therapy. Hysteroscopy and endometrial biopsies were utilized to establish maturation patterns, glandular epithelial mitosis rates, and macroscopic endometrial appearance. The results showed an increase in withdrawal bleeding with higher levels of progesterone, with those levels producing distinct secretory responses. However, incidence of endometrial hyperplasia after 5 years of E2/P therapy was independent of secretory changes and withdrawal bleeding, and was more related to the control of mitosis, which was seen even with low doses of progesterone. The authors conclude that a relatively low dose of P may be offered to women seeking hormone replacement therapy with similar levels of endometrial safety.