Efficacy and safety of a constant-estrogen, pulsed-progestin regimen in hormone replacement therapy

Objective-Two studies (Studies A and B) were conducted to measure efficacy and safety of constant 17 beta-estradiol (E-2), pulsed norgestimate (NGM) h ormone replacement therapy on bleeding and vasomotor symptoms in postmenopa usal women. NGM was pulsed in a 3-days-off/3-days-on fashion. Study A also assessed effects of treatment on vaginal cytology. Study Design-In two 360- day, multicenter, double-blind, parallel-group studies, 1,253 subjects were randomized to receive daily, unopposed E-2 1 mg or one of three constant e strogen, pulsed progestin regimens: E-2 1 mg/NGM 30 mu g, E-2 1 mg/NGM 90 m u g, or E-2 1 mg/NGM 180 pg. Results-Bleeding control improved over time in women treated with E-2 1 mg/NGM 90 mu g: 69% of women were free of bleedin g (irrespective of spotting) during month 1, 71% during month 6, and 80% du ring month 12. E-2 1 mg/NCM 30 mu g had a lower incidence of bleeding but p rovided inadequate endometrial protection. Among subjects with vasomotor sy mptoms at baseline, the percentage of asymptomatic subjects at the end of 3 months was 70% in the E-2 1-mg group and 76% in the E-2 1-mg/NGM. 90-mu g group. E-2 1 mg/NGM 90 mu g was at least as effective as E-2 1 mg alone in causing maturation of vaginal epithelial cells. All regimens were well tole rated. Conclusion-Pulsed dosing of NGM 90 pg for 3 days off and 3 days on a long with continuous administration of E-2 is effective in treating vasomot or symptoms and vulvovaginal atrophy, provides endometrial protection (i.e. , no cases of endometrial hyperplasia or cancer), and has a bleeding profil e acceptable to the majority of women studied.