Objective: To study the long-term effects (5 years) of intrauterine levonorgestrel administration as the progestin part of continuous combined postmenopausal hormone replacement therapy.Design: Prospective clinical study.Setting: Department of obstetrics and gynecology at a central hospital.Patient(s): Twenty postmenopausal women with an intact uterus who had no contraindications to hormone replacement therapy and who wanted to take amenorrhea-inducing hormone replacement therapy to relieve their climacteric symptoms.Intervention(s): A percutaneous E 2 gel containing 1.5 mg of E 2 was administered daily and a levonorgestrel-releasing intrauterine device was used. Endometrial thickness was measured by vaginal ultrasonography. Endometrial sampling was performed yearly.Main Outcome Measure(s): Clinical compliance, profiles of bleeding, and endometrial thickness and morphology were monitored during 5 years of follow-up.Result(s): Eighteen women completed 1 year of follow-up. Fifteen of these women were willing to continue the study, and 12 of them completed 5 years of follow-up. Spotting was frequent during the first 6 months of the study and declined thereafter. At 1 year, 80% of the women were totally amenorrheic. Of the 15 women who continued the study, 12 were totally amenorrheic and 3 had problems with bleeding. The mean endometrial thickness was =<3 mm during the study. Endometrial morphology showed epithelial atrophy accompanied by decidualization of the stroma in all 12 of the women who were followed up for 5 years.Conclusion(s): Intrauterine administration of progestin through a levonorgestrel-releasing intrauterine device is a good alternative as the progestin part of continuous combined hormone replacement therapy because it effectively opposes the estrogenic effects on the endometrium and induces amenorrhea in most cases.