More than just contraception : the impact of the levonorgestrel-releasing intrauterine system on public health over 30 years

Universal access to sexual and reproductive health services is essential to facilitate the empowerment of women and achievement of gender equality. Increasing access to modern methods of contraception can reduce the incidence of unplanned pregnancy and decrease maternal mortality. Long-acting reversible contraceptives (LARCs) offer high contraceptive efficacy as well as cost-efficacy, providing benefits for both women and healthcare systems. The levonorgestrel-releasing intrauterine system (LNG-IUS) first became available in 1990 with the introduction of Mirena (LNG-IUS 20), a highly effective contraceptive which can reduce menstrual blood loss and provide other therapeutic benefits. The impact of the LNG-IUS on society has been wide ranging, including decreasing the need for abortion, reducing the number of surgical sterilisation procedures performed, as well as reducing the number of hysterectomies carried out for issues such as heavy menstrual bleeding (HMB). In the context of the COVID-19 pandemic, Mirena can provide a treatment option for women with gynaecological issues such as HMB without organic pathology, minimising exposure to the hospital environment and reducing waiting times for surgical appointments. Looking to the future, research and development in the field of the LNG-IUS continues to expand our understanding of these contraceptives in clinical practice and offers the potential to further expand the choices available to women, allowing them to select the option that best meets their needs.Non peer reviewe

Thirty years of mirena : A story of innovation and change in women's healthcare

Since its introduction in 1990, the levonorgestrel-releasing intrauterine system (LNG-IUS) has played a key role in shaping the healthcare landscape of women. Here we explore the development of the first LNG-IUS (Mirena (R)) and the early clinical trials that demonstrated its potential. We highlight the contraceptive and therapeutic benefits of Mirena (R), and discuss how clinical practice has been changed since the introduction of LNG-IUS and other long-acting reversible contraceptive methods. The history of Mirena (R) is rich in innovation and has also paved the way to the development of smaller intrauterine systems with lower hormone doses. Along with Mirena (R), these newer LNG-IUS contribute to improving contraceptive choices for women, allowing them to select the option that is right for them and that meets their needs no matter their age, parity or circumstances.Non peer reviewe

The effect of a combined indomethacin and levonorgestrel-releasing intrauterine system on short-term postplacement bleeding profile: a randomized proof-of-concept trial

Background Long-acting reversible contraceptives, including hormonal levonorgestrel-releasing intrauterine systems, are the most effective methods of reversible contraception. However, unfavorable bleeding, particularly during the first months of use, is one of the most important reasons for discontinuation or avoidance. Minimizing this as early as possible would be highly beneficial. Nonsteroidal anti-inflammatory drugs inhibiting prostaglandin synthesis are known to reduce bleeding and pain at time of menses. A levonorgestrel-releasing intrauterine system has been developed with an additional reservoir containing indomethacin, designed to be released during the initial postplacement period. Objective This proof-of-concept study aimed to establish whether the addition of indomethacin to the currently available levonorgestrel-releasing intrauterine system (average in vivo levonorgestrel release rate of 8 μg/24 h during the first year of use) reduces the number of bleeding and spotting days during the first 90 days of use compared with the unmodified system. The dose-finding analysis included 3 doses of indomethacin—low (6.5 mg), middle (12.5 mg), and high (15.4 mg)—to determine the ideal dose of indomethacin to reduce bleeding and spotting days with minimal side-effects. Study Design This was a multicenter, single-blinded, randomized, controlled phase II trial conducted between June 2018 and June 2019 at 6 centers in Europe. Three indomethacin dose-ranging treatment groups (low-, middle-, and high-dose indomethacin/levonorgestrel-releasing intrauterine system) were compared with the unmodified levonorgestrel-releasing intrauterine system group, with participants randomized in a 1:1:1:1 ratio. The primary outcome was the number of uterine bleeding and spotting days over a 90-day reference (treatment) period. Secondary outcomes were the number of women showing endometrial histology expected for intrauterine levonorgestrel application and the frequency of treatment-emergent adverse events. Point estimates and 2-sided 90% credible intervals were calculated for mean and median differences between treatment groups and the levonorgestrel-releasing intrauterine system without indomethacin. Point and interval estimates were determined using a Bayesian analysis. Results A total of 174 healthy, premenopausal women, aged 18 to 45 years, were randomized, with 160 women eligible for the per-protocol analysis set. Fewer bleeding and spotting days were observed in the 90-day reference period for the 3 indomethacin/levonorgestrel-releasing intrauterine system dose groups than for the levonorgestrel-releasing intrauterine system without indomethacin group. The largest reduction in bleeding and spotting days was achieved with low-dose indomethacin/levonorgestrel-releasing intrauterine system, which demonstrated a point estimate difference of −32% (90% credible interval, −45% to −19%) compared with levonorgestrel-releasing intrauterine system without indomethacin. Differences for high- and middle-dose indomethacin/levonorgestrel-releasing intrauterine system groups relative to levonorgestrel-releasing intrauterine system without indomethacin were −19% and −16%, respectively. Overall, 97 women (58.1%) experienced a treatment-emergent adverse event considered related to the study drug, with similar incidence across all treatment groups including the unmodified levonorgestrel-releasing intrauterine system. These were all mild or moderate in intensity, with 6 leading to discontinuation. Endometrial biopsy findings were consistent with effects expected for the levonorgestrel-releasing intrauterine system. Conclusion All 3 doses of indomethacin substantially reduced the number of bleeding and spotting days in the first 90 days after placement of the levonorgestrel-releasing intrauterine system, thus providing proof of concept. Adding indomethacin to the levonorgestrel-releasing intrauterine system can reduce the number of bleeding and spotting days in the initial 90 days postplacement, without affecting the safety profile, and potentially improving patient acceptability and satisfaction