PREVENTION OF ENDOMETRIAL HYPERPLASIA BY PROGESTERONE DURING LONG-TERM ESTRADIOL REPLACEMENT - INFLUENCE OF BLEEDING PATTERN AND SECRETORY CHANGES

Objective: To determine the relative influences of induction of withdr awal bleeding, secretory transformation, and reduction of mitosis in g lands on prevention of endometrial hyperplasia during long-term hormon al replacement therapy. Design: Observational expanded clinical case r eport. Setting: Reproductive Endocrine Department of Hopital Necker, P aris, France, and Pathology Department of Women's Hospital, Los Angele s County and University of Southern California Medical Center, Los Ang eles, California. Patients: Postmenopausal women seeking treatment for symptomatic menopause. Interventions: Endometrial biopsy and/or ambul atory hysteroscopy. Main Outcome Measure: Endometrial histology includ ing progestational maturation patterns and glandular epithelial mitosi s rates. Macroscopic endometrial appearance. Results: The use of large r doses of E2 and P induced more marked secretory changes and more fre quent withdrawal bleeding than the lower doses. There was no evidence of endometrial hyperplasia after 5 years of E2/P replacement therapy i ndependently of bleeding pattern or progestational maturation. Consist ent reduction of mitosis rates in glandular epithelium was found after 9 or more days of P administration in each cycle. Conclusions: Contro l of endometrial growth is mainly related to control of mitosis in gla nds by a relatively low doses of P. Induction of withdrawal bleeding a nd endometrial secretory transformation, which require larger doses of Progesterone, do not provide additional benefit for prevention of hyp erplasia. Induction of amenorrhea with a relatively low dose of P may be offered to women seeking hormone replacement therapy with similar l evels of safety.