Objective: To assess the acceptability, ease of insertion, tolerance and associated bleeding of a novel intrauterine progestogen-releasing system, combined with transdermal estradiol, in postmenopausal women.
Design: An open non-comparative study of 294 postmenopausal women with an intact uterus at 27 centers in six countries.
Method: All subjects had requested treatment for menopausal symptoms and had received transdermal estradiol 50 microg/day by patch and an experimental intrauterine system (MLS) releasing levonorgestrel 10 microg/day. Details of the insertion were recorded and subsequent bleeding, side-effects and adverse events were documented on a daily diary. Endometrial thickness was measured by transvaginal ultrasound scan prior to insertion of the MLS and after 12 months. The study is of 3 years duration. This report summarizes the results after the first year.
Results: The median age of the subjects was 52.6 years (range 41.7-59.6 years), 90% were within 3-5 years of menopause and 78% had previously used hormone therapy (HT). The MLS was inserted at the first attempt in 297/294 (94%) subjects and was facilitated by dilatation of the cervical canal in 65 (22%) subjects. Local anesthesia was given to 30 (10%) subjects. Of the 17 with a failed first insertion, two subjects did not want a second attempt, in 14 a second attempt succeeded, facilitated by cervical dilatation in seven and local anesthetic in three subjects. There was one failed insertion. Investigators rated 80% of first insertions as easy, 14% as slightly difficult and 6% as very difficult. The second insertion was easy in 9/15 subjects, slightly difficult in 4/15 and very difficult in one (data from one subject missing). During insertion, 34% subjects had no pain, 49% said it was mild, in 15% it was moderate and in 2% the pain was severe. At 12 months, one MLS had been expelled. Spotting was the most common form of bleeding and this decreased from a median of 9 to 0 days at 4 months, although 10% of subjects continued to report spotting up to 12 months. Bleeding days were few and mainly in the first 2 months. At the end of month 11, 66.8% were amenorrheic and 87% non-bleeding. Only nine subjects discontinued because of bleeding. There was no correlation between the bleeding profiles and number of years since menopause, previous HT use or body mass index. The median endometrial thickness at entry to the study (without HT) was 2.6 mm and 3.4 mm at 12 months. Of the adverse events, after the pain associated with insertion, headache was the next most common at 13.3% and mastalgia was experienced by 7.8% of subjects. Overall, the dropout rate was low at 28 subjects (9.5%). There were favorable changes in the serum lipid profile consistent with the effects of estradiol and suggesting minimal attenuation by the intrauterine progestogen. Conclusion This interim report of a 3-year study has confirmed that the menopausal levonorgestrel intrauterine system is easy to insert and is well tolerated by postmenopausal women.