Effect of a unique constant-estrogen, pulsed-progestin hormone replacement therapy containing 17beta-estradiol and norgestimate on endometrial histology.

Objective: To evaluate the effect of a 17beta-estradiol(E2)/norgestimate (NGM) HRT regimen, which provides constant estrogen in combination with pulsed progestin administration, on endometrial histology in healthy postmenopausal women 40 to 65 years of age who had experienced natural menopause at least 12 months before the start of the study.

Methods: A total of 1,253 postmenopausal women were randomized to receive either continuous 1 mg E2, or constant estrogen, pulsed progestin regimens of 1 mg E2/30 microg NGM, 1 mg E2/90 microg NGM, or 1 mg E2/180 microg NGM (3 days on, 3 days off) in a 12-month, multicenter, double-blind study. Endometrial biopsies were obtained pre- 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 hyperplasia were diagnosed in subjects who received E2 1 mg/NGM 90 microg or E21 mg/NGM 180 microg, whereas 74 (28%) and 16 (6%) cases of endometrial hyperplasia were diagnosed in subjects who received continuous E2 1 mg and E2 1 mg/NGM 30 microg, respectively. A dose-related endometrial response to NGM was apparent (P < .001). The percentage of patients with inactive/atrophic endometrium increased with NGM dose.

Conclusion: The results of this study support the safety and efficacy of this unique HRT regimen and suggest that the minimal NGM dose required to protect the endometrium from hyperplasia in a pulsed progestin regimen consisting of continuous E2 1 mg is 90 microg.