With the total fertility rate in the United States at just over two children for every woman, one thing seems obvious: The “average” woman needs several decades of effective contraception during her fertile life span.1 The situation is even more compelling in Europe, where several countries are experiencing a decline in population. Clearly, women are choosing to have smaller families, or none at all, or are postponing childbearing longer than ever before.
In the past, many women opted for sterilization once childbearing was completed. Today, however, the sterilization rate is declining, in part because of the emerging use of long-acting, reversible contraception.2 The levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena) is one of these long-acting contraceptives. It also offers benefits besides contraception: It reduces the severity of heavy menstrual bleeding, requires no daily or monthly attention, and, when priced over its full 5-year lifetime, is economical. Because of its effect on heavy menstrual bleeding, for which it was FDA-approved in 2009, the LNG-IUS also is emerging as an alternative to endometrial ablation and hysterectomy.3-5
To elucidate the benefits and risks of the LNG-IUS and explore its ultra-long-term use, we contacted Oskari Heikinheimo, MD, PhD, an expert on the subject. Dr. Heikinheimo is adjunct professor of obstetrics and gynecology at Helsinki University Central Hospital in Helsinki, Finland, and an integral figure in early use of the LNG-IUS. In this interview, he discusses the LNG-IUS overall and offers insight from Scandinavia, which has a long history of LNG-IUS use.
Does the LNG-IUS provide effective contraception?
OBG Management: Let’s begin by focusing on the primary indication for the LNG-IUS— as a contraceptive. The device was approved as a contraceptive in the United States in 2001. That means we have a decade of experience. What have we learned?
Dr. Heikinheimo: We have considerably more than 10 years of experience with the LNG-IUS, as it was first approved in Finland in 1990 and in Sweden in 1992. We know that the system is safe and highly effective, with a 5-year cumulative pregnancy rate of 0.1%–0.5%.
OBG Management: Where does that statistic originate?
Dr. Heikinheimo: The safety and efficacy of the LNG-IUS were first established in a Finnish as well as a large European multicenter trial of more than 2,000 women. The women were 18 to 38 years old at the time of enrollment, of proven fertility, and used the system for as long as 5 years, providing 110,000 woman-months of exposure.6,7 These results were confirmed in several later studies, most recently in a large post-marketing study of more than 17,000 women and 58,000 woman–years.8
OBG Management: Were you involved in development of the LNG-IUS?
Dr. Heikinheimo: No, development of the LNG-IUS began in the 1970s—at that time I was attending elementary school. However, I do have the privilege of knowing the masterminds behind the LNG-IUS, most importantly Professor Tapani Luukkainen.
OBG Management: What amount of levonorgestrel is released by the LNG-IUS?
Dr. Heikinheimo: The progestin is released at a rate of approximately 20 μg daily when the LNG-IUS is first inserted, although that rate gradually declines, decreasing by approximately 50% after 5 years of use, when the system should be replaced.9
A stable serum concentration of levonorgestrel of 150 to 200 pg/mL is found within a few weeks of insertion. After 12, 24, and 60 months, that level is 180±66 pg/mL, 192±140 pg/mL, and 159±59 pg/mL, respectively.10
OBG Management: What is the mechanism of action of the LNG-IUS as a contraceptive?
Dr. Heikinheimo: It isn’t completely clear. It is thought that the system thickens the cervical mucus, preventing passage of sperm into the uterus. It may also inhibit sperm capacitation or survival, or alter the endometrium, or all of these things. A recent study from Los Angeles showed convincingly that sperm penetration through samples of mid-cycle cervical mucus, collected from women using the LNG-IUS, is zero.11 Thickening of cervical mucus plays an important role in the contraceptive efficacy of the LNG-IUS. The main mechanism of action is prevention of fertilization.
OBG Management: Can a woman who has used the LNG-IUS readily conceive once it is removed?
Dr. Heikinheimo: Yes. Approximately 80% of women who wish to become pregnant do so within 12 months after the device is removed.9 That figure is similar in women who have not used the LNG-IUS.
OBG Management: In the United States, in 2009, the LNG-IUS was approved for a second indication—to reduce heavy menstrual bleeding. What do we know about its efficacy in that regard?