LA JOLLA, CALIF. — American women and their physicians have given thumbs up to the levonorgestrel-releasing intrauterine system. The verdict came in a 29-center open-label trial, the first big test for the system in the United States, Dr. Jeffrey T. Jensen said in a poster presentation at the annual meeting of the Association of Reproductive Health Professionals.
The levonorgestrel-releasing intrauterine system (LNG IUS), a T-shaped polyethylene frame with a steroid reservoir, is marketed as Mirena and was approved by the Food and Drug Administration in 2000 for intrauterine contraception for up to 5 years.
Mirena was launched by Berlex in the U.S. market the following year; whereas it is approved in other countries for a number of indications, such as heavy uterine bleeding and endometrial hyperplasia, its sole U.S. indication is for intrauterine contraception.
“This study was done to gain experience for U.S. clinicians leading to the marketing of this very important and significant device,” said Dr. Jensen, who is an adviser to Berlex, which provided funding for this study.
“We waited many years for the levonorgestrel-releasing intrauterine system,” said Dr. Jensen, expressing the hope that the LNG IUS will soon receive FDA approval for additional indications.
In this 29-center study, 509 women met the eligibility criteria for inclusion in the intention-to-treat analysis. All but 2 of the women had successful IUS insertions, and 402 women completed the 1-year study. The mean age of participants was 32, and over half were white. All but 37 of the women had had more than a single prior delivery, and the average uterine cavity size was 7.8 cm.
Among the study findings were the following:
▸ Device insertion was successfully carried out on the initial visit 96% of the time.
▸ Investigators rated 92% of insertions as “easy,” while 68% of subjects reported “mild” or “no” pain at insertion.
▸ Based on a 7-point scale from very “dissatisfied” to “very satisfied,” 95% of subjects and 91% of providers rated the adequacy of product information at 6 or 7.
▸ More than four-fifths of subjects were “very satisfied” with the LNG IUS. Reasons for liking the product included ease of use, contraceptive reliability, and acceptable changes in bleeding patterns.
▸ The vast majority of investigators stated that between one and five insertions are necessary to feel comfortable with Mirena insertion.
“The reasons for noninsertion included cervical stenosis in one woman and a uterine cavity less than 6 cm in the other,” said Dr. Jensen, who is Leon Speroff professor of obstetrics and gynecology at the Oregon Health and Science University, Portland.
About half the women received premedication with ibuprofen, and only 6% of the subjects required cervical dilation, half as a planned portion of the insertion and half after difficulty with passing the device, he said.
Continuation rates at 3, 6, and 12 months were 95%, 87%, and 79%, respectively. Most discontinuations were due to adverse events, including complications with the device. There were 26 incidents of expulsion or accidental removal and no cases of perforation.
Bleeding results were similar to those in published international studies, Dr. Jensen said.
When the bleeding experience was divided into 90-day treatment intervals, the number of bleeding and spotting and bleeding-only days decreased throughout the study, with about 15% of subjects reporting amenorrhea and only 14% reporting spotting at the end of the 12-month period.
“Most women given the option of continuing with the device, which received FDA approval during the course of the study, opted to do so,” Dr. Jensen said.
Discussant Dr. David A. Grimes agreed that American women and their physicians have looked forward to Mirena's approval for a long time.
“Women deserve this product, and they now have it,” said Dr. Grimes, who disclosed that he serves on the Berlex speaker's bureau. Although the study provided no surprises, it showed the product to be effective, safe, and well tolerated, said Dr. Grimes, who is vice president of biomedical affairs for Family Health International.