Endometrial safety with a low-dose intrauterine levonorgestrel-releasing system after 3 years of estrogen substitution therapy

Abstract

Objective: To evaluate the pharmacodynamic effects of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), on the endometrium in 24 postmenopausal women using estrogen substitution therapy (EST) to suppress climacteric symptoms. Design: A 3-year non-comparative prospective clinical trial. Subjects: The treatment with the FibroPlant-LNG intrauterine system (IUS), releasing 14 μg of LNG per day, was part of a regimen for estrogen substitution therapy in symptomatic postmenopausal women to prevent endometrial proliferation and bleeding. The majority of women received percutaneous 17β estradiol, 1.5 mg daily, or an equivalent dose by patch or orally, on a continuous basis. Outcome measures: Menstrual pattern, endometrial histology and ultrasonographic evidence of endometrial suppression, after 3 years of use. Results: The endometrial histology specimen showed profound endometrial suppression with glandular atrophy and stroma decidualization in all women. On transvaginal ultrasound, this corresponds with a thin endometrium (<5 mm) and clinically with a “bleed-free” menstrual pattern or amenorrhoea. Conclusion: The results of this 3-year study in 24 postmenopausal women using EST suggest that the FibroPlant-LNG IUS is effective in causing strong suppression of the endometrium during the entire period of EST. Target delivery in the uterine cavity could be the preferred route of administering a progestin to oppose estrogen stimulation of the endometrium.