Effect of a unique constant-estrogen. Pulsed-progestin hormone replacementtherapy containing 17 beta-estradiol and norgestimate on endometrial histology

Objective-To evaluate the effect of a 17 beta-estradiol(E-2)/norgestimate ( NGM) HRT regimen, which provides constant estrogen in combination with puls ed progestin administration, on endometrial histology in healthy postmenopa usal women 40 to 65 years of age who had experienced natural menopause at l east 12 months before the start of the study. Methods-A total of 1,253 post menopausal women were randomized to receive either continuous 1 mg E-2, or constant estrogen, pulsed progestin regimens of 1 mg E-2/30 mu g NGM, 1 mg E-2/90 mu g NGM, or 1 mg E-2/180 mu g NGM (3 days on, 3 days off) in a 12-m onth, multicenter, double-blind study. Endometrial biopsies were obtained p re- and post-treatment, and were evaluated by at least 2 (if required, by 3 )pathologists who were blinded with respect to treatment and to each other' s diagnosis. Results-At the end of the study, no cases of endometrial hyper plasia were diagnosed in subjects who received E-2 1 mg/NGM 90 mu g or E(2) 1 mg/NGM 180 mu g, whereas 74 (28%) and 16 (6%) cases of endometrial hyperp lasia were diagnosed in subjects who received continuous E-2 1 mg and E-2 1 mg/NGM 30 mu g, respectively. A dose-related endometrial response to NGM w as apparent (P < .001). The percentage of patients with inactive/atrophic e ndometrium increased with NGM dose. Conclusion-The results of this study su pport the safety and efficacy of this unique HRT regimen and suggest that t he minimal NGM dose required to protect the endometrium from hyperplasia in a pulsed progestin regimen consisting of continuous E-2 1 mg is 90 mu g.