The levonorgestrel-releasing intrauterine system for endometrial protection during estrogen replacement therapy: a clinical review.
OBJECTIVE To investigate endometrial histology, bleeding, and the effects of replacing the levonorgestrel intrauterine system (LNG IUS, Mirena/Levonova, Leiras Oy, Turku, Finland) after 5 years of combined use with estrogen. DESIGN Prospective cohort study. SETTING Private outpatient clinic. PATIENT(S) Forty postmenopausal women started hormone replacement therapy with LNG IUS and either a patch (50 microg/24 h) or oral (2 mg) estradiol valerate protocol. Thirty-nine completed 12 months of treatment. Twenty-nine of them had used LNG IUS with continuous estradiol replacement therapy for 5 years. Seven of them volunteered to a 3-month treatment-free period before reinsertion; 22 opted for immediate reinsertion. INTERVENTION(S) Endometrial sampling for histology, endometrial thickness, and location of the LNG IUS by ultrasound at removal and after washout. The women completed bleeding diaries from 3 months prior to removal to 3 months after reinsertion. MAIN OUTCOME MEASURE(S) Endometrial histology was evaluated and estrogen and progestin effects were also investigated. Endometrial thickness was measured. Bleeding was examined based on bleeding diaries. The investigator and the women evaluated the insertion, removal, and reinsertion of the LNG IUS. RESULT(S) At 6 and 12 months endometrial histology was nonproliferative. At removal, all endometria were suppressed and a strong progestin effect was seen. The thickest endometrium was 3.6 mm. After washout, all seven endometria were atrophic. Before the IUS was replaced, 26 women were amenorrheic, whereas three had minor spotting. After replacement 5 women had no bleeding and an additional 10 women had only spotting. The bleeding or spotting discontinued within 18 days. The insertion of LNG IUS was characterized as easy by the investigator and it was well tolerated by the women. Cervical dilatation and/or paracervical blockade was used in 10 insertions. CONCLUSION(S) Intrauterine levonorgestrel effectively protects against endometrial hyperplasia. In most women it induces amenorrhea, which is only temporarily affected by replacement of the LNG IUS.