Objective: To determine whether a low dose of P delivered together with E 2 from a vaginal ring on a continuous schedule can prevent endometrial proliferation and yield a bleeding pattern dominated by amenorrhea.Design: Longitudinal clinical study.Setting: Three university hospitals.Patient(s): Fifty-five women 45 to 75 years of age, not hysterectomized, with E 2 levels of <20 pg/mL and hot-flash incidence of two or more per day in the past week.Intervention(s): A vaginal ring delivering approximately 150 μg/d of 17β-E 2 and approximately 5 mg/d or approximately 9 mg/d of P used continuously for 4 and 6 months.Main Outcome Measure(s): Endometrial thickness, bleeding pattern, and hot flash incidence.Result(s): Endometrial proliferation was prevented by both P doses. Bleeding incidence decreased. In months 4, 5, and 6, 8 of 12 women had no bleeding. Incidence of hot flashes and night sweats decreased quickly and significantly.Conclusion(s): A vaginal ring delivering E 2 and a low dose of P merits further study as a method for long-term hormone replacement therapy.