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Contraindications to the levonorgestrel-releasing intrauterine system according to organizational recommendations
Source publication
The levonorgestrel-releasing intrauterine system (LNG-IUS) is a safe, effective and acceptable form of contraception used by over 150 million women worldwide. It also has a variety of noncontraceptive benefits including treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The LNG-IUS has also been used in combination with estrogen...
Context in source publication
Citations
... It is also effective in treating dysmenorrhea and HMB. [5][6][7] It has been recommended as a treatment option for adenomyosis based on following mechanisms: (a) downregulation of estrogen receptors in both eutopic and ectopic endometrial glands; (b) decidualization of endometrium which subsequently dysmenorrhea, dyspareunia, chronic pelvic pain, and heavy menstrual bleeding. Managing symptoms is crucial, and medical approaches include levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG). ...
... 3 leads to atrophy of adenomyotic ectopic endometrium; and (c) reduction of prostaglandin production within the endometrium thereby reducing painful symptoms in adenomyosis. 6,7 LNG-IUS is associated with a more significant reduction in painful symptoms, uterine volume, and HMB than COCs. [2][3][4][5] It is also used after adenomyomectomy or other conservative surgical procedures to prevent recurrence. ...
Plain language summary
Comparison of effectiveness and safety of Mirena (LNG-IUS) with dienogest for treatment of adenomyosis
Adenomyosis is a condition affecting women, typically aged 40–50, but its incidence is rising in younger women, impacting fertility. It causes painful symptoms like dysmenorrhea, dyspareunia, chronic pelvic pain, and heavy menstrual bleeding. Managing symptoms is crucial, and medical approaches include levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG). LNG-IUS is reversible contraception, approved for eight years, effectively treating symptoms. DNG, a newer progestin, is effective for endometriosis, but evidence for adenomyosis is limited. This single-center, open-label randomized clinical trial compared LNG-IUS and DNG in treating adenomyosis. Women over 20 with pelvic pain were diagnosed using ultrasound and met specific criteria. After informed consent, participants were assigned randomly to LNG-IUS or DNG groups. Treatment outcomes, including pelvic pain, quality of life (QoL), and adverse effects, were assessed over 12 weeks. Out of 84 assessed, 74 women were recruited, with 34 in each group analyzed. After 12 weeks, both groups showed significantly reduced pelvic pain (VAS scores), but no significant difference was found between the groups. LNG-IUS resulted in a significantly greater reduction in heavy menstrual bleeding (HMB), whereas DNG showed better improvement in overall QOL. Adverse effects were similar in both groups, with hot flushes reported in the DNG group. This study is one of the few comparing LNG-IUS and DNG for adenomyosis, finding both effective for symptom relief. Although LNG-IUS was superior in reducing HMB, DNG showed better overall improvement in QoL. Safety profiles were similar. Previous studies support the efficacy of DNG in reducing adenomyosis symptoms. To conclude, both LNG-IUS and DNG effectively alleviate adenomyosis symptoms, with LNG-IUS superior in reducing heavy menstrual bleeding and DNG showing better overall improvement in QOL. DNG is a viable and effective alternative to LNG-IUS.
... A recent meta-analysis of prospective studies by Abbas et al. demonstrated that LNG-IUDs effectively reduced symptom severity, uterine volume, and endometrial thickness, while also improving laboratory outcomes [137]. The proposed mechanism of action is based on the decidualization and atrophy of the endometrium and downregulation of ERs due to high progestin release [138]. There is ongoing debate regarding the optimal duration of treatment for ADM, with efficacy reported for durations between 1 and 6 years [139]. ...
Adenomyosis (ADM) is a multifaceted uterine pathology characterized by the ectopic infiltration of endometrial tissue into the myometrium, afflicting approximately 20% of women in the reproductive age group seeking gynecological care. This condition manifests as a range of debilitating symptoms, including dysmenorrhea, menorrhagia, impaired fertility, and heightened susceptibility to miscarriage and obstetric complications. Substantial research has been dedicated to exploring its underlying molecular mechanisms and developing non-invasive precision medical therapies. ADM is primarily characterized by a dysregulation in sex-steroid hormone homeostasis, particularly estrogen and progesterone. However, emerging evidence suggests that additional endocrine mediators and disruptors may exert contributory roles in the etiology of ADM. Furthermore, genetic and epigenetic alterations of endocrine signaling pathways have been implicated as prevailing mechanisms underlying the development and progression of the disease. The present review aims to provide an updated and comprehensive overview of the current understanding of the pathophysiology of ADM, with a particular emphasis on the dysregulated hormonal milieu and the potential involvement of endocrine disruptors. By elucidating these intricate molecular mechanisms, this review seeks to pave the way for novel research directions in the development of targeted therapeutic strategies for ADM management.
... The Levonorgestrel-Releasing Intrauterine delivery system (LNG-IUS) is an effective reversible contraceptive device lasting up to 5 years that can be used to treat several gynecological conditions. The most frequent adverse drug reactions of LNG-IUS are menstrual irregularities and changes in bleeding patterns; however, it has been associated with various undesirable side effects, such as ovarian cysts, acne, weight gain, depression, and decreased libido (2). Therefore, alongside the undeniable benefits and safety of such devices, concerns have arisen regarding the potential impact of these contraceptives on mood disorders, particularly the development of depression (3)(4)(5)(6). ...
This case illustrates the adverse cognitive and affective effects associated with the use of an intrauterine hormonal contraceptive, which could be confused with symptoms of early onset dementia. We present a case of a 42-year-old woman diagnosed with seronegative spondyloarthropathy who subsequently developed anxiety and depressive symptoms after the implantation of a Levonorgestrel-Releasing Intrauterine System (LNG-IUS). Three years later, she began to experience memory and attentional failures, refractory pain, and severe depression. The progression of psychiatric symptoms led to a diagnosis of bipolar affective disorder and treatment with antidepressants and anxiolytics. Due to cognitive and psychiatric symptoms, autoimmune encephalitis was considered, but no improvement was shown with treatment. Early onset dementia was suspected, and a brain PET scan revealed frontal lobe hypometabolism. An adverse effect of LNG-IUS was considered; after its removal, mood and cognitive function improvements were observed. This case report emphasizes the importance of considering organic causes of unexplained psychiatric manifestations and highlights the potential impact of hormonal interventions on mental health.
... IUCs are frequently associated with bleeding symptoms, ranging from menorrhagia to amenorrhea (4)(5)(6). In a secondary analysis of 1,947 Chilean C-IUD users, pain (38%) and bleeding (68%) declined gradually, peaking at nine weeks, but remained substantial, with 33% and 48% of women reporting these symptoms, respectively, after 39 weeks (4). ...
... Many women requesting C-IUD removal did not differ by perceived severity of pain or bleeding from those continuing the C-IUD (4). The LNG-IUS is associated with reduced menstrual pain and bleeding, often resulting in amenorrhea or irregularity (5). Among the USA CHOICE cohort, 7% of 1,925 women selecting an IUC discontinued within six months, with no statistically significant difference by IUC type. ...
Introduction:
While young women in South Africa may navigate both HIV infection and pregnancy risks, intrauterine contraceptive (IUC) use is low. Though IUCs have low failure rates, concerns exist about whether the IUC is an appropriate method choice for women living with HIV (WLHIV). In this qualitative study, we explore WLHIVs' experiences of using IUC and reasons for discontinuation.
Methods:
This qualitative study included in-depth interviews (IDIs) with 17 WLHIV who electively discontinued their allocated IUC while participating in a randomized controlled trial comparing the safety of the levonorgestrel intrauterine system (LNG-IUS) and the copper intrauterine device (C-IUD) in Cape Town, South Africa. The transcripts were coded and emergent themes were grouped to examine women's experiences with IUC use and reasons for discontinuation, highlighting experiential differences between the two methods.
Results:
Women's experience with the allocated IUC related most commonly to bleeding and/or abdominal pain just after insertion. Most C-IUD discontinuers, but only one LNG-IUS discontinuer, complained of pain and/or increased bleeding as the main reason for removal. Three women (two LNG-IUS, one C-IUD) requested removal because they desired pregnancy, while two others discontinued due to fears the IUC was exacerbating non-gynecologic conditions (hypertension, diabetes). Generally, women acknowledged advantages of IUC use and many expressed their desire to continue use if not for the side effects.
Conclusions:
In the South African context, IUC use for WLHIV should be promoted with specific counseling considerations. Both providers and potential users should receive specific information about potential menstrual-related side effects and countering common misperceptions to enable informed contraceptive decision-making.
... The LNG-IUS has not been approved for use in women with fibroids distorting the uterine cavity, congenital uterine anomaly, in women with pelvic infection, and in suspected malignancies. 6 The basal endometrial mucosa quickly absorbs levonorgestrel released by the LNG IUS., and may become detectable in plasma, 15 mins after insertion. The LNG targets the endometrium and decreases the menstrual blood loss and pain by uniform suppression of endometrial proliferation and decidualisation of stroma. ...
Heavy menstrual bleeding (HMB), is one of the most frequently encountered problem in the gynaecology OPD. It can significantly affect women’s quality of life and overburden health-care systems. The Levonorgestrel Releasing Intrauterine System (LNG-IUS) is a highly effective long-acting reversal contraceptive, also useful for controlling HMB and promoted by National Institute for Health and Care Excellence (NICE).
This prospective interventional study conducted upon 30 women, with heavy menstrual bleeding, of 30-50 years’ age, reporting in the outpatient department of a tertiary health care facility unit “between” January 2018 to June 2019. Women, who met inclusion and exclusion criteria were our study population. Data was collected during follow up at 1, 3 and 6 month and all the association were tested by mean, proportion and percentages. Chi-square test was used for comparing categorical result and p-value of less than 0.05 was considered as statistically significant. Calculation was made by using IBM SPSS 26 version of statistical software.
Majority of women were from 40-45 years’ age group. Pictorial Blood Loss Assessment Chart (PBAC) score was calculated in 30 women who underwent LNG IUS insertion.There was significant reduction (p<0.05) in the mean PBAC score at 3and 6month compared to their initial value after LNG-IUS insertion.
LNG IUS is effective and can be used as first line measure for treatment of HMB.
... A description of the adverse effects of the LNG-IUS is beyond the scope of this review; the reader may refer to review articles on the subject (e.g., [110,[164][165][166]). ...
We undertook a literature review of the use of levonorgestrel-releasing
intrauterine devices when utilized for heavy menstrual bleeding and/or dysmenorrhea
... Usually, IUSs are inserted into the uterine cavity during the first seven days of the menstrual cycle. It is also considered safe to administer IUSs immediately after uncomplicated spontaneous or induced firsttrimester and second-trimester abortions [2,13,41]. For postpartum insertion, it is recommended by the WHO to insert IUSs four weeks after childbirth to avoid the risk of perforation and expulsion [41]. ...
... It is also considered safe to administer IUSs immediately after uncomplicated spontaneous or induced firsttrimester and second-trimester abortions [2,13,41]. For postpartum insertion, it is recommended by the WHO to insert IUSs four weeks after childbirth to avoid the risk of perforation and expulsion [41]. LNG-IUSs are inserted to a uterine depth of 6-10 cm which is predetermined using ultrasound. ...
Levonorgestrel intrauterine systems (LNG-IUSs) are complex drug-device combination products designed to release a hormonal contraceptive drug for up to 7 years. These drug delivery systems offers a great promise as a modern method of long-acting reversible contraceptives (LARCs) to improve women’s health. Unfortunately, there are some scientific challenges associated with the development of these products which are among the major reasons contributing to the availability of relatively few IUS products on the market. This review summarizes the formulation considerations (drug and excipient attributes), manufacturing methods, advances in characterization and in vitro drug release testing of IUSs, as well as factors influencing drug release from IUSs. A critical discussion on the major challenges to IUS product development is presented. Specifically, insights on bioequivalence evaluation, in vitro-in vivo correlation (IVIVC) establishment, and regulatory challenges are detailed. Lastly, methodological tools to overcome some of these hurdles to product development are proposed. The knowledge furnished through this review will be helpful towards obtaining better product understanding. Such understanding will facilitate the development of these complex drug products, as well as their regulatory approval process.
... Another explanation for the lack of association between LNG-IUD and BPE observed in about half of women could be the fact that hormone release by LNG-IUDs decreases over time; the two LNG-IUDs used in our cohort have a therapeutic window of 3 and 5 years, respectively [1,32,33]. Since this is a retrospective analysis, we could not control the time interval between LNG-IUD placement and the MRI study; in almost half of the women, the exact date of LNG-IUD placement was not known. Current guidelines mandate the removal or replacement of LNG-IUDs after the recommended time, and all 25 women for whom the date of LNG-IUD placement was known had their LNG-IUDs placed within the recommended time. ...
Objectives
Levonorgestrel-releasing intrauterine contraceptive devices (LNG-IUDs) are designed to exhibit only local hormonal effects. There is an ongoing debate on whether LNG-IUDs can have side effects similar to systemic hormonal medication. Benign background parenchymal enhancement (BPE) in dynamic contrast–enhanced (DCE) MRI has been established as a sensitive marker of hormonal stimulation of the breast. We investigated the association between LNG-IUD use and BPE in breast MRI to further explore possible systemic effects of LNG-IUDs.
Methods
Our hospital database was searched to identify premenopausal women without personal history of breast cancer, oophorectomy, and hormone replacement or antihormone therapy, who had undergone standardized DCE breast MRI at least twice, once with and without an LNG-IUD in place. To avoid confounding aging-related effects on BPE, half of included women had their first MRI without, the other half with, LNG-IUD in place. Degree of BPE was analyzed according to the ACR categories. Wilcoxon-matched-pairs signed-rank test was used to compare the distribution of ACR categories with vs. without LNG-IUD.
Results
Forty-eight women (mean age, 46 years) were included. In 24/48 women (50% [95% CI: 35.9–64.1%]), ACR categories did not change with vs. without LNG-IUDs. In 23/48 women (48% [33.9–62.1%]), the ACR category was higher with vs. without LNG-IUDs; in 1/48 (2% [0–6%]), the ACR category was lower with vs. without LNG-IUDs. The change of ACR category depending on the presence or absence of an LNG-IUD proved highly significant ( p < 0.001).
Conclusion
The use of an LNG-IUD can be associated with increased BPE in breast MRI, providing further evidence that LNG-IUDs do have systemic effects.
Key Points
• The use of levonorgestrel-releasing intrauterine contraceptive devices is associated with increased background parenchymal enhancement in breast MRI.
• This suggests that hormonal effects of these devices are not only confined to the uterine cavity, but may be systemic.
• Potential systemic effects of levonorgestrel-releasing intrauterine contraceptive devices should therefore be considered.
... GnRH agonists are effective in causing systemic hypoestrogenism to reduce the size of adenomyosis and improve adenomyosis-associated symptoms [153][154][155], whereas the side effects of GnRH agonists (menopausal symptoms) limit their use. LNG-IUD has been considered most effective and successfully used to treat adenomyosis because it is efficient in suppressing menstrual bleeding [156][157][158][159][160]. The efficacy of LNG-IUD is generally higher than other progestin-based treatments [151,152]. ...
Estrogen and progesterone and their signaling mechanisms are tightly regulated to maintain a normal menstrual cycle and to support a successful pregnancy. The imbalance of estrogen and progesterone disrupts their complex regulatory mechanisms, leading to estrogen dominance and progesterone resistance. Gynecological diseases are heavily associated with dysregulated steroid hormones and can induce chronic pelvic pain, dysmenorrhea, dyspareunia, heavy bleeding, and infertility, which substantially impact the quality of women’s lives. Because the menstrual cycle repeatably occurs during reproductive ages with dynamic changes and remodeling of reproductive-related tissues, these alterations can accumulate and induce chronic and recurrent conditions. This review focuses on faulty progesterone signaling mechanisms and cellular responses to progesterone in endometriosis, adenomyosis, leiomyoma (uterine fibroids), polycystic ovary syndrome (PCOS), and endometrial hyperplasia. We also summarize the association with gene mutations and steroid hormone regulation in disease progression as well as current hormonal therapies and the clinical consequences of progesterone resistance.
... The hormonal IUD is a T-shaped device comprising a cylinder containing 52 mg of levonorgestrel, with an average release of 14µg of levonorgestrel every 24 hours of the life of the IUS 14 . The Mirena® LNG IUS that is produced by Bayer Healthcare Pharmaceuticals Inc is indicated to have an effective duration of up to 5 years. ...
... The IUS functions locally in the uterus by thickening the cervical mucus and suppressing endometrial proliferation, thus inhibiting conception. The IUS is known to have both contraceptive and non-contraceptive health benefits in the treatment of menorrhagia, endometriosis, and endometrial hyperplasia 14 . The method is very convenient as it requires nothing else to be done regularly to maintain contraception until after five years when the device can be replaced. ...
Background : The hormonal intrauterine device or intrauterine system (IUS) also known as the levonorgestrel intrauterine system (LNG-IUS) is a highly effective hormonal intra-uterine contraceptive. However, services offering the method are not widely available in Nigeria and little evidence exists on the dynamics of its use. We examined the continuation rate and satisfaction with the IUS among the user population.
Methods : This prospective longitudinal phone survey involved a baseline survey of users at two-weeks post-insertion of the LNG IUS, recruited from 40 clinics across 17 states in Nigeria, with a follow-up survey at the 3 rd and 12 th months. A total of 208 users were interviewed at baseline, 98 at three months, and 73 at 12 months. User family planning and the IUS use experiences were elicited, as well as the continuation rate and satisfaction with the method at three and 12 months.
Results : At three- and 12 months post-insertion, 96.9% (95% CI: 91.3, 99.3) and 91.8% (95% CI: 82.9, 96.9), respectively, reported still using the LNG IUS, with none out of the few users who discontinued the method reporting a method failure. Discontinuation was mainly a result of the experience of menstrual bleeding or amenorrhea (25.0%), experiences of pain with the method (18.8%), and partner complaining about strings (16.7%). High satisfaction with the LNG IUS (76.5% at three months and 86.3% at 12 months post-insertion) was reported. Satisfaction with LNG IUS was significantly associated with not having breast tenderness/pain (88.2%) and no vaginal bacterial infection (87.5%) at 12 months compared to experiencing breast tender/pain (50.0%) and vaginal infection (0.0%) (p<0.05).
Conclusion : High user continuation and satisfaction with IUS indicates the positive potential of the method as a contraceptive in Nigeria.
