New clinical data on consecutive use of the levonorgestrel-releasing intrauterine system

Consecutive use of the levonorgestrel-releasing intrauterine system is increasing

The levonorgestrel-releasing intrauterine system (LNG-IUS) was developed by Finnish researchers in collaboration with the Population Council, leading to approval in Finland in 1990. It has been on the market since the mid-1990s in most European countries and was approved in 2001 in the USA. It is currently marketed on several indications in more than 120 countries worldwide. The LNG-IUS is one of the most effective contraceptive methods with a Pearl index of 0.2 at 1 year and a cumulative failure rate of 0.7 at 5 years. Besides contraception, LNG-IUS has been approved for the treatment of idiopathic menorrhagia, heavy menstrual bleeding (HMB) and endometrial protection during estrogen-replacement therapy for menopausal symptoms in more than 100 countries [1]. The licensed duration of LNG-IUS use is 5 years. Owing to its high efficacy, safety, long action and typical bleeding pattern, the LNG-IUS has become the prototype of a bleeding-free contraceptive.

Repeated use of the LNG-IUS is increasing rapidly. Currently, of all LNG-IUS users, the proportion of women who are using their second device is approximately 25% in Europe, with rates of up to 42% in individual countries [2]. Yet repeat use of the device has been relatively scarcely studied.

Recently, we have reported data from an international prospective multicenter study on consecutive use of the LNG-IUS [3]. It is well known that initial LNG-IUS use in particular may be associated with a period of irregular bleeding, that the effect on bleeding is individual, and that the experienced bleeding pattern is highly associated with the acceptability of LNG-IUS among users. Therefore, we focused particularly on the bleeding patterns and on the predictors for bleeding during consecutive use of the LNG-IUS [3,4]. In addition, the removal and insertion procedures of the LNG-IUS were evaluated [5].

Bleeding is even further reduced during consecutive use of the LNG-IUS

Owing to its pronounced effects on the endometrium, characterized by suppression of the endometrial glands accompanied by stromal decidualization, the LNG-IUS is effective at reducing menstrual bleeding [6]. The bleeding pattern typically associated with the use of the LNG-IUS includes an initial period of irregular bleeding/spotting during the first months of use. Thereafter, the number of bleeding and spotting days reduces and the rate of amenorrhea increases, reaching approximately 20% after 1 year of use [7].

A high rate (up to 60%) of amenorrhea has previously been shown during consecutive use of the LNG-IUS [8]. Similarly, our recent study showed a reduction in bleeding or maintenance of amenorrhea during the first year of the second consecutive LNG-IUS [3]. Of special clinical importance was the observation that the initial period of irregular bleeding/spotting typically seen during the first months of use with a first LNG-IUS was absent when insertion of a second LNG-IUS was performed immediately following removal of the first LNG-IUS.

Can the bleeding pattern in consecutive use of the LNG-IUS be predicted?

Knowledge of factors that may predict the bleeding pattern during the LNG-IUS is of high clinical importance to improve counselling. A number of possible predictors for bleeding pattern during LNG-IUS use have been identified [4,9]. In first-time LNG-IUS users, it was shown that baseline menstrual bleeding duration of less than 5 days, use of the LNG-IUS for contraception instead of treatment of menorrhagia, and absence of menorrhagia before insertion were associated with a higher rate of oligoamenorrhea at 1 year after LNG-IUS insertion [9]. In an analysis of predictive factors of the bleeding pattern during the first year of use of a second LNG-IUS among fertile-aged women who used their first LNG-IUS either for contraception or for the treatment of HMB or menorrhagia, demographic factors such as age, parity, BMI, indication of LNG-IUS use or smoking could not be identified as predictors for bleeding or spotting. Women with uterine fibroids or a bleeding pattern of more than 9 days of spotting or any bleeding at baseline (defined as the 3 months prior to insertion of the second LNG-IUS) had more bleeding or spotting days at baseline and during the first year of the second LNG-IUS use than women without fibroids, with baseline amenorrhea or with less than 9 days of spotting. However, the number of bleeding/spotting days was still observed to decrease progressively during the first year of use, with the exception of women with fibroids, in whom the trend of continuous reduction of bleeding/spotting was not observed.

LNG-IUS insertion procedure

Fear of painful or difficult insertion of an intrauterine device may make women and providers reluctant to choose this method for contraception and other indications. Therefore, studies exploring facilitating methods, such as cervical priming, are needed in women with an increased risk for difficult insertions, such as perimenopausal women and nulliparous women. It is also commonly believed that long-term use of the LNG-IUS may make the insertion of a consecutive IUS more difficult. Theoretically, insertion of an LNG-IUS in the case of amenorrhea and reduced cervical mucus might be more difficult than in women with regular menstrual cycles. In the recent study, we focused on the ease of LNG-IUS removal and insertion as well as the associated pain symptoms. We found that insertion of a second consecutive LNG-IUS was judged to be easy and associated with no or only mild pain in a vast majority of women [5]. Cervical priming with sublingual misoprostol 3 h prior to insertion of the IUS did not result in any further improvement in the ease of insertion compared with placebo. Moreover, women who received misoprostol did not report less pain than those who received placebo treatment.

Thus, simultaneous removal and insertion of the LNG-IUS is easy, uncomplicated and practical in the great majority of cases, and should be the standard of care.

Acceptability

Among European women of reproductive age, approximately 10% use a long-acting reversible contraceptive method, and the LNG-IUS and copper intrauterine device are the most popular contraceptives in this class [10]. In the aforementioned international multicenter trial on consecutive use of LNG-IUS, the overall satisfaction with the LNG-IUS at the 12-month visit was more than 98%. This was also reflected in the high degree (>90%) of subject satisfaction with the bleeding pattern at the end of the first year of use of the second LNG-IUS, regardless of baseline bleeding pattern or indication (HMB or contraception). Strikingly, the highest satisfaction rate was described among the women reporting amenorrhea, where it reached 100%. Menstrual disturbances have a huge impact on the quality of life for many women. Today, the view of monthly bleeding as natural and healthy among women is rapidly changing. Relief from bleeding or reduced blood loss is becoming more and more popular, not only for women suffering from HMB but for any woman of reproductive age. Medical management of HMB allowing preservation of fertility is increasingly needed as more women postpone childbirth until later in life. The benefits of amenorrhea also include freedom from other cycle-related problems such as dysmenorrhea and premenstrual symptoms.

Summary

Use of the LNG-IUS is increasing worldwide on several indications. Thus, an increasing number of women are now using not only their first but also their second, third or even fourth LNG-IUS. New data on consecutive use of the LNG-IUS show that the insertion procedure is usually uncomplicated and associated with no or only mild pain in the majority of women. The initial period of irregular bleeding typically observed with a new LNG-IUS is avoided and bleeding/spotting is further reduced during consecutive use of the LNG-IUS. The overall satisfaction with the LNG-IUS at 1 year was very high (>98%). This was also reflected in the high degree of satisfaction with the bleeding pattern during use of the second LNG-IUS, regardless of baseline bleeding pattern. Most satisfied were the women reporting amenorrhea, where the satisfaction rate reached 100%.

Financial & competing interests disclosure

Kristina Gemzell-Danielsson and Oskari Heikinheimo received support from Bayer Schering Pharma AG (Germany) to conduct the clinical trials that are cited. They also serve on medical advisory boards, and occasionally give presentations for Bayer and MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.