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Background: Adenomyosis is a gynaecological lesion that impairs female fertility and contributes to reduced quality of life. There are several surgical and medical options for the management of this lesion; however, women who wish to conceive opt for medical therapies such as the levonorgestrel intrauterine device (LNG-IUS) and dienogest, which have various outcomes. To date, there is no consensus regarding which is more effective., Objectives: To compare the effectiveness of LNG-IUS and dienogest for the management of adenomyosis, and explore the risk of occurrence of known side effects for both treatments., Design: Systematic review and meta-analysis exploring the effectiveness of LNG-IUS and dienogest for the management of adenomyosis., Methods: A literature search was conducted using PICO guidelines and EMBASE, PubMed/MEDLINE, Scopus and Web of Science databases. Only clinical trials were collected and analysed., Results: Of the 792 studies that were initially identified, six were eligible for inclusion in this study. The studies included a total of 707 women; of these, 270 were treated with LNG-IUS, 354 were treated with dienogest, and 83 were controls. All the studies were from Asia (Bangladesh n = 1, China n = 2, India n = 1, Japan n = 1, South Korea n = 1). Dienogest was found to reduce pelvic pain significantly, evidenced by a lower visual analogue scale score, compared with LNG-IUS. Also, dienogest led to a significant reduction in uterine volume compared with LNG-IUS. However, subjects in the LNG-IUS group had significantly higher levels of haemoglobin than those in the dienogest group. Nonetheless, the occurrence of side effects such as weight gain, breast tenderness/distension, headache, insomnia/sleep disorder, depression/mood disorder, skin disorder/acne, and coital discomfort/reduced libido were comparable in both treatment groups., Conclusion: Dienogest may be more effective than LNG-IUS for the management of adenomyosis, as it shows a superior effect in the reduction of pelvic pain and uterine volume. As only six studies were included in the present meta-analysis due to the paucity of data in the literature, it is recommended that well-designed randomized controlled trials comparing the effectiveness of dienogest with LNG-IUS should be conducted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps., Methods: Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy., Results: Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a + LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a + LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision + LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision + LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5 years are needed., Conclusions: Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To map and assess evidence regarding use of the levonorgestrel-releasing intrauterine system (LNG-IUS) and its association with breast cancer, we conducted a systematic review and meta-analysis. A search strategy was developed using the terms "Levonorgestrel-releasing," "LNG-IUS," "intrauterine system," and "breast cancer. The electronic databases searched were MEDLINE, Embase, Cochrane Library, Latin American & Caribbean Health Sciences Literature, and Google Scholar for studies published until August 2020. We included observational studies: prospective or retrospective cohort, case-control, and cross-sectional. A total of 494 studies were identified, 294 studies were evaluated by title and abstract, and 262 were excluded because they did not meet the inclusion criteria. A total of 32 studies were read in full, and 24 were excluded. Thus, eight studies were included in the systematic review. The meta-analysis included four studies (two cohort and two case-control studies). Two subgroup analyses were performed for different study designs. The estimated relative risk for the two cohort studies (144,996 cases), with moderate-quality evidence, was 0.93 (95% confidence interval [CI], 0.840-1.03). The odds ratio estimated for the two case-control studies (5556 cases and 35987 controls), with moderate-quality evidence, was 1.07 (95% CI, 0.91-1.26). Evidence of an increased risk of breast cancer was not observed in levonorgestrel-releasing intrauterine system users., (Copyright © 2021. Published by Elsevier Inc.)

Research Question: How does use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in infertile women with endometrial hyperplasia without atypia affect endometrial hyperplasia regression and pregnancy rates compared with oral medroxyprogesterone acetate (MPA)?, Design: This prospective cohort study included 215 infertile women with an indication for assisted reproductive technology (ART) and a diagnosis of endometrial hyperplasia without atypia. Endometrial hyperplasia was diagnosed by hysteroscopic endometrial biopsy. At the time of first- and second-line treatment, patients were offered therapy with either oral MPA 10 mg daily or LNG-IUS. Follow-up biopsies were scheduled after 90 days' treatment. After endometrial hyperplasia regression, patients were admitted to IVF/intracytoplasmic sperm injection (ICSI) cycles., Results: Baseline characteristics and confounders including age at diagnosis, body mass index and duration of infertility did not differ between LNG-IUS users and control participants and were accounted for using propensity score weighting. Endometrial hyperplasia regression rate at first follow-up was higher in the LNG-IUS group than the oral progestins group (28/28, 100% and 110/187, 58.8%; P < 0.001), while that after second-line treatment was comparable between the two groups (89/91, 97.8% and 122/124, 98.4%; P = 0.22). Clinical pregnancy rate, miscarriage rate and cumulative live birth rate following ART in patients ever receiving LNG-IUS were similar to those of patients receiving only MPA (34% versus 39.5%, 22.6% versus 34.7% and 26.4% versus 25.8%)., Conclusion: Endometrial hyperplasia regression is greater in women receiving LNG-IUS compared with oral MPA, while live birth rates following ART are comparable between the two groups. The use of LNG-IUS does not jeopardize the chances of pregnancy in women seeking fertility treatment., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to assess the pain scores at the insertion of the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) among nulligravidas, parous women with previous vaginal delivery and parous women with elective caesarean-delivery without any previous labour or cervix dilation., Materials and Methods: The present research is a prospective, single-cohort study that included 413 women aged 15-49 years who opted for LNG-IUS placement for contraception or treatment of heavy menstrual bleeding. Women who participated in the present study were not submitted to any pharmacological pain-relieving intervention to perform the procedure. Pain at insertion was evaluated by using a Visual Analogue Scale (VAS). Pain was classified as absent (0), mild (1-3), moderate (4-6), or severe (7-10). The women were divided as: (1) nulligravidas, (2) parous women with a previous vaginal delivery, or (3) parous women with elective caesarean-delivery without any previous labour or cervix dilation., Results: Nulligravidas women presented a higher mean pain score, when compared to women with elective caesarean-delivery and women with previous vaginal delivery (6.6 ± 2.0 vs 5.5 ± 2.1 and 3.9 ± 2.4, respectively; p  < 0.001). Nulligravidas and women with elective caesarean-delivery were more likely to have pain classified as moderate or severe (in relation to absent or mild) than women with previous vaginal delivery ( p  < 0.001). Multiple Linear Regression Analysis demonstrated that 29.5% of all variability of the pain score was explained by two predictor/independent variables: nulligravidas or women with elective caesarean and difficulty at IUD insertion., Conclusions: Women with previous vaginal delivery had lower pain scores at LNG-IUS insertion when compared to nulligravidas and women with elective caesarean-delivery without any previous labour.

Background: Endometrial cancer is the second most frequent genital malignancy in women, which is showing a constant rise all over world. Endometrial hyperplasia is the precursor of endometrial cancer. Levonorgestrel intrauterine system is the first line management in patients with endometrial hyperplasia without atypia. Metformin has shown to reverse endometrial hyperplasia, but its effectiveness and safety in endometrial hyperplasia is uncertain., Objective: To compare the efficacy in terms of histopathological response, clinical response and safety at the end of 6 months in patients with endometrial hyperplasia without atypia managed with Levonorgestrel intrauterine system alone versus patients managed with Levonorgestrel intrauterine system plus metformin., Methods: The randomized control trial was conducted on 51 cases of endometrial hyperplasia without atypia. Twenty-five subjects were prescribed metformin 500mg twice daily with Levonorgestrel intrauterine system and 26 subjects, with Levonorgestrel intrauterine system only for 6 months. At the end of 6 months, endometrial sampling was performed for histopathological response., Results: Clinical response was observed in 23 of 25 subjects in metformin group and 22 of 24 in Levonorgestrel only group. The metformin group responded significantly with amenorrhea (p= 0.0053), while Levonorgestrel only group responded with regular cycles (p=0.027). At the end of study, of 46 subjects available for histopathological evaluation, 100% subjects in metformin group and 95.45% in Levonorgestrel only group (p=0.47826) showed complete response. The metformin group had a significant reduction in body mass index at end of study [P = 0∙023, 95% confidence interval (-1.7802, -0.1418)]., Conclusion: No significant difference in regression of endometrial hyperplasia was observed on adjunctive use of metformin but a significant reduction in BMI was observed. Use of metformin in obese patients may improve the treatment response.

This study aimed to evaluate the effect of a levonorgestrel-releasing intrauterine system (LNG-IUS) on the sexual function of women. Participants who had abnormal uterine bleeding (AUB) complaints with LNG-IUSs were included (study registration: Kanuni Sultan Suleyman Training and Research Hospital, 2018/10/34). The demographic data of all participants were recorded. The female sexual function index (FSFI) questionnaire was used to participants before the insertion of LNG-IUSs and 6 months after its insertion. FSFI scores were calculated at both timepoints and were compared. The total FSFI score after LNG-IUS insertion was significantly higher than the total FSFI score application ( p  < .001). The scores of the desire, arousal, lubrication, orgasm, satisfaction and pain categories significantly increased after LNG-IUS compared to those before LNG-IUS. As a result, the present study demonstrated that after LNG-IUS insertion, these women had higher FSFI scores.Impact Statement What is already known on this subject? There are many publications in the literature comparing the effects of LNG-IUSs, IUSs, OCs and other contraceptive methods on female sexuality. However, there are markedly few studies that compare sexual function before and after LNG-IUS insertion. What do the results of this study add? The total FSFI score after LNG-IUS insertion was significantly higher than the total FSFI score before the insertion ( p < .001). The scores of the desire, arousal, lubrication, orgasm, satisfaction and pain categories significantly increased after LNG-IUS insertion compared to those before the application. The number of participants with FSFI scores ≥26.5 before LNG-IUS insertion was 17 (12.5%), and this number increased to 71 (52.5%) after the application What are the implications of these findings for clinical practice and/or further research? This study contributes to the literature because there are few researches that compare sexual function before and after LNG-IUS insertion. As a result of our study, sexual dysfunction decreased after LNG-IUS, and the scores increased in all sub-groups together with the total FSFI scores.

Objective: Up to 60% of women discontinue using the levonorgestrel-releasing intrauterine system (LNG-IUS) within 5 years because of bleeding irregularities, pain and/or systemic progestogenic adverse effects. The aim of the study was to assess treatment options for bleeding irregularities in women using the 52 mg LNG-IUS., Methods: Database searches of Medline, Embase/Ovid and the Cochrane Library were carried out, and journals were searched by hand, for relevant studies published from database inception to March 2020. Inclusion criteria were randomised controlled trials (RCTs), prospective cohort studies and case-control studies of premenopausal women using the LNG-IUS and receiving medical treatment for bleeding irregularities. Screening, data extraction and quality assessment of retrieved articles were carried out independently by two pairs of reviewers. The primary outcome was the reduction of bleeding/spotting days., Results: Of the 3061 studies identified, eight met our inclusion criteria: six RCTs and two prospective cohort studies. The eight studies enrolled a total of 677 women who were treated with tamoxifen, mifepristone, ulipristal acetate, naproxen, oestradiol, mefenamic acid, tranexamic acid or the progesterone receptor modulator CDB 2914. The results of our analysis indicated that naproxen may be effective for the prophylactic treatment of bleeding immediately (<12 weeks) after LNG-IUS insertion (high level of evidence). Oestradiol may be effective in treating ongoing bleeding irregularities >6 months after insertion (low level of evidence)., Conclusion: Evidence for the medical treatment of (ongoing) bleeding irregularities during use of the LNG-IUS is lacking and more research is needed on the topic.

Objectives: Few studies, with contradictory results, evaluate intrauterine contraceptives (IUC) and sexual function specifically. This study compares perception of sexual desire related to IUC use and aspects of sexual function in women who use the Lng-IUS with those using the Cu-IUD., Study Design: A secondary analysis regarding IUC use based on a larger cross-sectional survey of contraceptive use in Sweden, conducted in 2013. In total, 153 IUC users (103 Cu-IUD and 50 Lng-IUS users) answered the questionnaire. The only inclusion criterion was intrauterine contraceptive use., Main Outcome Measures: Were self-reported sexual desire changes related to contraceptive method. We also analysed aspects of sexual functioning; sexual desire level, sexual activity, orgasm frequency, satisfaction with sex life and satisfaction of desire level., Results: A negative effect on sexual desire due to contraceptive method was reported by 28% of the Lng-IUS users and by 10.1% of the Cu-IUD users (p < 0.05). Results were more marked after adjusting for age, body mass index, depression, parity, switching behaviour, and partnership (OR 5.0; CI: 1.8-13.8). The adjusted odds of reporting low sexual desire level (never or almost never feeling sexual desire) (OR 3.5; CI: 1.1-11.2) as well as low satisfaction with sex life (OR 2.7; CI: 1.2-6.3) was higher in the Lng-IUS group (adjusted for same confounders as above)., Conclusions: The women in this study using the Lng-IUS more often report negative sexual desire effects of their contraception as well as lower sexual desire level compared with women using the Cu-IUD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This research was conducted to assess the long-term outcomes of a combination treatment of High-intensity focused ultrasound (HIFU) ablation, gonadotropin-releasing hormone analogs (GnRHa) and Levonorgestrel-releasing intrauterine system (LNG-IUS) for women with adenomyosis (AD). Methods: One hundred and forty-two patients with AD were enrolled and treated with HIFU conservative treatment in combination with adjuvant therapy of GnRHa and LNG-IUS. All the cases were followed up to 5 years after treatment. The volumes of uteri, AD lesions, and menstrual blood, and dysmenorrhea scores were measured. Also, the incidences of recurrence and complications were recorded. Results: Both the uterine and lesion volumes significantly decreased after treatment. The uterine volume gradually reduced after treatment, reaching the lowest level of 122.07 ± 44.12 cm 3 at 12 months after treatment, with an average reduction rate of 45%, and then increased slightly, maintaining a reduction rate of about 35% compared with the baseline level. Similar decreases in AD lesion volumes, dysmenorrhea scores, and menstrual flow were also demonstrated. Hemoglobin levels increased. Moreover, the long-term recurrence rates were low, with 5.68% and 7.91% in dysmenorrhea and menorrhagia, respectively. No serious complications or adverse events were reported. Conclusions: HIFU ablation, in combination with GnRHa and LNG-LUS, might be a safe and effective alternative in the treatment for women with adenomyosis.

Introduction: Lack of awareness of reproductive hormone-related mood changes in the general population or limited acknowledgement of their existence by health care providers regularly contribute to fears or misconceptions about the link between hormonal contraception and potential mood changes. Recent media discussion linked the levonorgestrel intrauterine system (LNG-IUS 20 µg/d) to elevated cortisol levels and the possibility of panic attacks, anxiety, mood changes, sleep disturbance and restlessness. Efficacy of the LNG-IUS is based primarily on local effects but systemic effects, including a potential increase in mood symptoms, are a known risk and reflected in the product labelling for all LNG-IUS products., Objective: There is a need to improve communication to the public and health care providers around potential risk of mood disorders in order to facilitate 'informed choice' amongst women considering an LNG-IUS as their contraceptive method and directly address the fears of women currently using an LNG-IUS., Results: We propose a simple and brief, step-by-step process that can be embedded within current counselling that explores and clarifies the potential risk of developing mood symptoms prior to placement of LNG-IUS. It also addresses concerns from women using an LNG-IUS who either present with mood symptoms or are concerned about potential onset., Conclusion: Mood symptoms with use of LNG-IUS are uncommon; however, all women, including those who may experience an increased sensitivity to certain progestins, should be counselled appropriately to raise awareness of the potential risk within an informed discussion around effectiveness, benefits and possible adverse events.

Objectives: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an underused contraceptive method in sub-Saharan Africa. A recent market assessment in Kenya found that if a more affordable version of the method were available it may increase demand and uptake of the method. We therefore aimed to examine attitudes and perceptions around the LNG-IUS and experiences of method use, including exploring attributes such as bleeding changes, contraceptive-related amenorrhoea and perceived non-contraceptive benefits., Methods: Qualitative interviews were conducted among 29 women who were current or recent users of the LNG-IUS, and among a subset (n = 9) of their husbands/partners., Results: Our findings indicate that women's main reason for choosing the LNG-IUS for contraception was their perception that the method had fewer side effects compared with other contraceptive methods. Women had favourable attitudes towards using the LNG-IUS. Husbands were also very positive about their partner's use of the method., Conclusion: Understanding the motivations and experiences of early adopters of the LNG-IUS can help inform the development of demand creation and communication strategies to influence uptake and continuation of the LNG-IUS both in Kenya and perhaps more broadly. Communication efforts that emphasise the positive attributes of the LNG-IUS could help promote wider use of the method, especially if new, more affordable product(s) become available.

Background/aim: Progestin therapy has been accepted as therapy for low- and medium-risk endometrial hyperplasia. The aim of this study was to investigate the efficacy of the low-dose levonorgestrel-impregnated intrauterine system (LNG-IUS) 13.5 mg (Jaydess®, Bayer Pharmaceuticals, Berlin, Germany) as therapy for endometrial hyperplasia., Patients and Methods: A total of 21 women with histologically-verified endometrial hyperplasia were prospectively treated with LNG-IUS Jaydess. Therapy duration was 6 months (n=16) or 3-6 weeks (n=5) depending on individual risk (low- and medium-risk versus high-risk) for co-existent or future endometrial carcinoma. Paired endometrial biopsies were sampled prior to and after therapy and classified according to the WHO94 classification system and D-score., Results: All women with low- and medium risk endometrial hyperplasia had-therapy response. In the group of women with high-risk endometrial hyperplasia only 40% (two out of five) obtained a therapy response., Conclusion: Low-dose LNG-IUS Jaydess was proven to be an excellent therapy option for low- and medium-risk endometrial hyperplasia. For patients with high-risk endometrial hyperplasia hysterectomy or LNG-IUS therapy under close surveillance is advised., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The aim of the study was to investigate the impact of the long-acting reversible contraception (LARC) levonorgestrel-releasing intrauterine system (LNG-IUS 13.5 mg) on sexual function and quality of life (QoL) in women after having undergone abortion for unintended pregnancy., Methods: In a prospective controlled study, 128 women aged 16-35 years received counseling to adopt LNG-IUS contraception after termination of pregnancy. The Visual Analog Scale (VAS), the Short Form-36 questionnaire (SF-36), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to investigate, respectively, pelvic pain levels, QoL, sexual function and sexual distress of these women at baseline (T0) and at 6 (T1) and 12 (T2) months after LNG-IUS placement., Results: Sixty-six (51.6%) women adopted a SARC method, mainly because of the cost of the LNG-IUS. They constituted the control group. The study group consisted of 62 (48.4%) women. Improvement of QoL was observed at T1 (p < .05) and T2 (p < .01). Moreover, sexual function improved and dyspareunia decreased over the study period compared to baseline (p < .001). Dysmenorrhea measured by VAS improved at T1 and at T2 (p < .001). The women of the control group did not experience statistically significant changes at T1 and T2 compared to T0 (p = NS)., Conclusions: Women who underwent termination of pregnancy experienced positive changes in QoL and sexual function during LNG-IUS use. These results have to be confirmed in larger studies. However, not all women could adopt the LNG-IUS because of the cost of the contraceptive.

Aim: To evaluate the efficacy and safety of levonorgestrel-releasing intrauterine system (LNG-IUS) in the long-term treatment of heavy menstrual blood loss in women unrelated to intrauterine pathology., Methods: One hundred and six parous women aged 33-48 years with recurrent heavy menstrual bleeding (HMB) participated in this study. The women were followed up for 24 months and were assessed for intensity of bleeding both for pre- and post-insertion periods. An LNG-IUS was inserted in each patient within 7 days of the start of menstrual flow. The women were followed up at 1, 3, 6, 12, 18, and 24 months following the insertion of the intrauterine device., Results: One hundred and two women completed the follow-up period and had a significant reduction in the amount of menstrual blood loss. The LNG-IUS was well tolerated by all women. Pre-treatment of the use of the LNG-IUS, endometrial biopsy patterns for irregular proliferative endometrium and for atypical simple hyperplasia were 34/106 (32.08%) and 61/106 (57.55%) respectively and after treatment no abnormal pathologic findings were determined (p < 0.001)., Conclusion: Our findings indicate that the LNG-IUS is effective for significantly reducing the amount of menstrual blood loss in women with HMB., (© 2017 S. Karger AG, Basel.)

Objectives: To report placement success rate, and ease and pain associated with placement, of the levonorgestrel-releasing intrauterine system (LNG-IUS) 8 using the modified EvoInserter® placement device., Study Design: This was a pooled analysis using data from three previously reported Phase III studies in nulliparous (83.3%) or parous (16.7%) women aged 12-35 years (N=965). LNG-IUS 8 was placed using the modified Evolnserter®. The main outcomes assessed were placement success, ease of placement as reported by healthcare professionals (HCPs), pain at placement as reported by participants, and assessment of the EvoInserter® placement device by HCPs., Results: LNG-IUS 8 placement using the modified EvoInserter® with an insertion tube diameter of 3.8 mm was successful in 99.5% of subjects. HCPs rated the placement procedure as "easy" in 91.6% of cases. Placement pain was reported as absent by 19.1% of participants, as mild by 39.3%, as moderate by 31.6%, and as severe by 10.0%. Overall 89.2% of HCPs completely agreed that the device was easy to prepare and 85.7% completely agreed that placement of an LNG-IUS was easy/simple with the EvoInserter®. Post hoc exploratory analyses indicated a significant association between ease/pain of placement and patient age and between pain of placement and parity., Conclusions: The modified Evolnserter® was associated with a high placement success rate, ease of placement, and manageable pain, and was assessed to have a user-friendly design. These findings suggest that the EvoInserter® may remove some concerns among HCPs about difficult placement of LNG-IUSs, thereby encouraging increased uptake of an effective contraceptive., Implications Statement: Results reported in this study further strengthen evidence of the high placement success rate, ease of deployment, and manageable pain associated with the modified EvoInserter® placement device. These findings might reduce concerns among HCPs about placement of LNG-IUSs, meaning uptake of such contraceptives is increased., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To ascertain whether menstrual irregularities among users of levonorgestrel releasing intrauterine system (LNG-IUS) and depot medroxyprogesterone acetate (DMPA), were associated with changes in uterine artery Doppler indices or not., Methods: This three-year prospective observational study included 102 women using LNG-IUS and 104 women using DMPA for contraception. Participants were followed at regular intervals over three years with performance of transvaginal ultrasound to measure uterine artery pulsatility index (PI) and resistance index (RI) before starting the method and at six months, 12 months, two and three years thereafter. Data was collected and tabulated., Results: Significant changes in uterine artery PI and RI were detected. PI indices were reduced after six months of use in both groups and elevated significantly at 12 months in both groups compared to initial values (p < .001) while RI significantly reduced after six months in both groups and elevated significantly at 12 months, two and three years in both groups compared to initial values (p < .001). Both PI and RI significantly reduced in women suffered abnormal uterine bleeding and significantly elevated in women experienced amenorrhea irrespective of the method used (p < .001)., Conclusions: LNG-IUS and DMPA induce hemodynamic changes in the uterine arteries denoting positive correlation with menstrual irregularities. Larger multicentre studies are warranted to potentiate our findings.

Objective: To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use., Study Design: In this Phase III study, 2885 nulliparous and parous women aged 18-35 years were randomized to LNG-IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction., Results: From August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months., Conclusion: In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG-IUS 12 offers women a low-dose contraceptive option for up to 5 years., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective method of contraception, while also providing various non-contraceptive benefits. Although targeted primarily to adults, there is increasing experience in its use in adolescence. The aim of this review is to assess the available information on LNG-IUS usage in adolescence., Methods: We conducted an online search on MEDLINE and SCOPUS from inception to May 24, 2015. All studies that examined LNG-IUS use in teen populations were eligible for inclusion. Primary outcome measures included description of indications for LNG-IUS usage and relevant efficacy. Secondary outcomes included complications, such as device-related problems (perforation and expulsion) and other adverse events (pelvic inflammatory disease, PID). Acceptability of the LNG-IUS was also estimated through evaluation of continuation rate and reasons for removal were assessed., Results: Twenty-one studies met our inclusion criteria. We identified only one randomized controlled trial (RCT). All other twenty studies were observational. Pregnancy rates ranged from 0 to 2.7%. Management of heavy or/and painful periods was successful in 92-100%. Menstrual manipulation in patients with developmental delay was achieved in over 93% of cases. Expulsion rates ranged from 0 to 13% and pelvic infection/cervicitis between 0 and 2.7%. There were no reported uterine perforations., Conclusion: Usage of the LNG-IUS in teen populations appears to be safe and efficacious both in terms of contraception and menstrual management. However, more robust evidence is needed so as to provide firm confirmation on benefits and potential side effects.

Objective: The objective was to assess whether patient-perceived pain during the insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) depends on the timing during the menstrual cycle., Design: A stratified two-armed non-inferiority randomised controlled trial., Setting: Large teaching hospital in Veldhoven, the Netherlands., Sample: From October 2013 to May 2014, 60 nulliparous and 60 multiparous women were randomised. Eight women withdrew after randomisation and before insertion took place: therefore, data from 112 women were collected and analysed., Methods: Women were randomised to the groups 'during menstruation' (i.e. days 1-7 of menstruation) or 'outside menstruation' (i.e. any day of the cycle after menstruation without the presence of vaginal blood loss) in a ratio of 1 : 1., Main Outcome Measures: The primary outcome was pain during insertion, measured by the visual analogue scale (VAS, 0-100 mm). Second, we analysed ease of insertion, bleeding pattern, satisfaction, pregnancy, and expulsion rate. The follow-up time was 3 months., Results: The mean VAS score for nulliparous women was 74 mm (95% confidence interval, 95% CI 67-81) in the 'during menstruation' group, compared with 66 mm (95% CI 59-74) in the 'outside menstruation' group (P = 0.14). The mean VAS score for multiparous women was 30 mm (95% CI 20-40) in the 'during menstruation group', compared with 43 mm (95% CI 32-53) in the 'outside menstruation' group (P = 0.08). There was no difference between the stratified 'during menstruation' group and the 'outside menstruation' group with regards to ease of insertion, satisfaction, bleeding pattern, and median spotting and bleeding days for the use of the LNG-IUS 3 months after insertion., Conclusions: As we did not find that the level of pain perceived during insertion was higher during menstruation, compared with outside menstruation, we conclude that the LNG-IUS can be inserted at any time during the menstrual cycle, especially in the case of nulliparous women., Tweetable Abstract: We conducted an RCT on time of insertion of LNG-IUS. We conclude that the LNG-IUS can be inserted at any time., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Objectives: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women., Methods: Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit., Results: Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group., Conclusions: LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

Objective: The use of a levonorgestrel intrauterine system (LNG-IUS) is useful in preventing pregnancy and for the treatment of menstrual disturbances. A smooth or symptom-free transition to and through menopause is possible when LNG-IUS is combined with estrogen therapy. Unfortunately the majority of physicians are generally unaware of this usefulness combined hormonal therapy in the pre-, peri- and postmenopausal women., Design and Method: Based on long-term clinical experience with LNG-IUS in the form of Femilis®, 104 women where followed from the premenopause through the menopausal transition into the postmenopause. These perimenopausal women received supplemental 17 β-estradiol by gel or patch, or orally as estradiol valerate. Patients received one or two separate Femilis insertions at 5 year intervals. Main outcome measures included acceptability and continued use of the combined regimen for the treatment of climacteric symptoms and for prevention of cardiovascular disease, osteoporosis and other adverse effects caused by estrogen deprivation., Results: The average age at insertion was 48 years (range 28-58) and the total duration of use was 137 months (range 80-161). The Femilis LNG-IUS was well tolerated as the number of removals for LNG-IUS-related reasons was low. The LNG-IUS was well retained in the uterine cavity as no expulsions were observed. Seven women were lost to follow-up. Eighty-six women (82%) opted for replacement of an LNG-IUS at expiry after 5 years and continued with the estrogen therapy., Conclusion: Intrauterine progestogen delivery for endometrial suppression in combination with estrogen therapy in the symptomatic perimenopausal women is highly practical as it combines the benefits of prevention of endometrial proliferation and treatment of menorrhagia and hyperplasia, if present. In addition, the contraceptive effect of locally administered LNG is highly desirable as many perimenopausal women run considerable risk of unintended pregnancy. For these reasons, the author views this regimen as one of the most effective, safest and best accepted route resulting in high patient compliance. It is important to convey this message to general practitioners as well as women.

Objective: To compare the levonorgestrel intrauterine system (LNG-IUS 8), which has an average levonorgestrel release rate of ∼8 μg/24 hours during the first year (total levonorgestrel content 13.5 mg; Jaydess/Skyla), with the etonogestrel (ENG) subdermal implant (total content, 68 mg) with regard to the 12-month discontinuation rate (primary outcome)., Design: Randomized, open-label, phase III study., Setting: Thirty-eight centers in six European countries., Patient(s): Study population of 766 healthy nulliparous and parous women aged 18-35 years., Intervention(s): The LNG-IUS 8 or the ENG implant., Main Outcome Measure(s): Discontinuation rate, by treatment group, at Month 12., Result(s): The 12-month discontinuation rates were 19.6% and 26.8% in the LNG-IUS 8 and ENG implant groups, respectively. The -7.2% difference was statistically significant (95% confidence interval -13.2%, -1.2%). Fewer women in the LNG-IUS 8 group than in the ENG implant group discontinued because of increased bleeding (3.2% vs. 11.3%) or adverse events (14.3% vs. 21.8%). At 12 months, more women in the LNG-IUS 8 group than in the ENG implant group were "very/somewhat satisfied" with their bleeding pattern (60.9% vs. 33.6%) and reported a preference to use their study treatment after study completion (70.1% vs. 58.5%)., Conclusion(s): The LNG-IUS 8 was associated with a significantly lower 12-month discontinuation rate compared with the ENG implant; mainly because ENG implant users frequently discontinued due to increased bleeding. More LNG-IUS 8 users than ENG implant users reported being "very/somewhat satisfied" with their bleeding pattern, and reported a preference to continue using their study treatment after the study., Clinical Trial Registration Number: NCT01397097., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the safety profile of the low-dose levonorgestrel intrauterine system (LNG-IUS) total content 13.5mg (average approximate release rate 8μg/24h over the first year; LNG-IUS 8; Jaydess®) in adolescents., Study Design: In a Phase III study in 36 European centers, 304 healthy nulliparous or parous postmenarcheal adolescents (12-17years) received LNG-IUS 8 for 12months. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included: serious TEAEs, adverse events of special interest, overall user satisfaction, discontinuation rate at 12months, and Pearl Index., Results: LNG-IUS 8 placement was successful in 303/304 participants (99.7%). Overall, 82.6% of participants reported TEAEs, and serious TEAEs and serious study drug-related TEAEs were reported by 7.6% and 1.0% of participants, respectively. No cases of pelvic inflammatory disease, ectopic pregnancy, or uterine perforation were reported. No pregnancies were reported during the 12-month study. At Month 12/study end, the overall user satisfaction rate was 83.9%. Overall, 51 participants (16.8%) prematurely discontinued the study before 12months; 13.8% of participants discontinued owing to TEAEs., Conclusions: No new or unexpected safety events were associated with the low-dose LNG-IUS 8. The safety profile of LNG-IUS 8 in adolescents was consistent with that previously reported in adults. The high overall user-satisfaction rate at study end and the low discontinuation rate over 12months demonstrate that LNG-IUS 8 is a highly acceptable contraceptive method among adolescents., Implications: This study is the first to assess the low-dose levonorgestrel intrauterine system LNG-IUS 8 (average approximate release rate 8μg/24h over the first year and total content 13.5mg) specifically in females<18years of age and confirms the safety and efficacy of LNG-IUS 8 in an adolescent population., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Although the pathophysiology of adenomyosis has not been clarified, it is thought to be related to ectopic endometrium, which depends on hormonal regulation. The levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for the medical treatment of adenomyosis. However, the underlying molecular mechanisms by which LNG-IUS ameliorates adenomyosis pathology remain unclear. This study was designed to compare the expression levels of steroid receptor coregulators in human endometrium of control and participants with adenomyosis and to determine whether LNG-IUS modulated their expression. Immunohistochemistry with H-scores was performed. Steroid receptor coactivators were shown to have significantly decreased expressions at the secretory phase in the LNG-IUS group when compared to the other groups. Expression of transcriptional intermediary factor 2 was lower in the LNG-IUS group than in both the control group (P = .015) and the untreated adenomyosis group (P = .019) during the secretory phase. Amplified in breast cancer 1 expression was higher in the stromal cells of the untreated adenomyosis group than in those of the controls (P = .017) during the secretory phase; however, levels were lower in the LNG-IUS group (P = .005). Nuclear receptor corepressor expression increased during the proliferative phase and decreased during the secretory phase in untreated adenomyosis; this pattern was reversed in the control and LNG-IUS groups. Thus, an altered expression of steroid receptor coregulators may play a role in adenomyosis development and treatment., (© The Author(s) 2015.)

Introduction: This study compares the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a low-dose combined oral contraceptive (COC) in reducing adenomyosis-related pain and bleeding., Materials and Methods: A randomized clinical trial included 62 participants complaining of pain and bleeding that was associated with adenomyosis. Participants were randomly assigned to either LNG-IUS or COC treatment. The outcomes included the improvement of pain using a visual analogue scale, menstrual blood loss using a menstrual diary and estimated uterine volume by ultrasound for 6 months of treatment. We also compared uterine arteries and intramyometrial Doppler indices before and 6 months after treatment with both LNG-IUS and COCs., Results: Both treatments significantly reduced pain after 6 months of use; however, the reduction was greater in the LNG-IUS group (from 6.23±0.67 to 1.68±1.25) compared with the COCs group (from 6.55±0.68 to 3.90±0.54). Both treatment arms significantly decreased the number of bleeding days, uterine volume and Doppler blood flow in the uterus from before to after treatment. These effects were more significant in the LNG-IUS arm compared with the COC arm., Conclusion: Both LNG-IUS and COCs decreased the pain and menstrual bleeding that is associated with adenomyosis. However, LNG-IUS is more effective than the COCs in reducing pain and menstrual blood loss. This effect may be secondary to the decrease in uterine volume and the increase in blood flow resistance., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A prospective multicenter trial has been started in Korea to evaluate the diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and curettage in patients treated with progestin for endometrial hyperplasia. For conservative treatment of endometrial hyperplasia, orally administered progestins are most commonly used method with various treatment regimens and more recently, the levonorgestrel-releasing intrauterine system also has been used successfully to treat endometrial hyperplasia. However, there is no report about the accuracy of endometrial sampling during hormonal treatment for follow-up evaluation of endometrial hyperplasia. Patients with histologically confirmed endometrial hyperplasia are offered hormonal treatment with any one of the following three options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle, continuous oral medroxyprogesterone acetate 10 mg/day or insertion of levonorgestrel-releasing intrauterine system. Histological surveillance is performed at 3 months or 6 months following initial treatment. Endometrial tissues are obtained via endometrial aspiration biopsy using a pipelle and dilatation and curettage. In the case of levonorgestrel-releasing intrauterine system, endometrial aspiration biopsy will be done with levonorgestrel-releasing intrauterine system in uterus and then, after the removal of levonorgestrel-releasing intrauterine system, dilatation and curettage will be done. The biopsy findings will be compared. The primary endpoint is to compare the pathological outcome of endometrial aspiration with dilatation and curettage. The secondary endpoint is the response rate with three types of progestin treatment at 6 months., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Study Question: Is small uterine cavity size as assessed by ultrasonography associated with bleeding problems or pain in nulligravid women using intrauterine contraception, or do other factors affect these parameters?, Summary Answer: Among levonorgestrel intrauterine system (LNG-IUS) users, small uterine cavity size is not associated with worsened clinical outcome, but is beneficial as women with the smallest cavity measurements were frequently amenorrhoeic and painless at the end of the first year but among copper intrauterine device (IUD) users, no associations between uterine cavity dimensions and clinical outcome were found., What Is Known Already: Nulligravid and nulliparous women have smaller uterine dimensions than parous women. Previously, many studies have revealed increased discontinuation rates of IUD use as a result of bleeding, pain or expulsion in these women, while recent studies with current models of IUS/IUDs indicate similar continuation and satisfaction rates irrespective of parity., Study Design, Size, Duration: In a pilot study, 165 adult nulligravid women requesting their first IUD between 1 January 2011 and 31 July 2012 were given a free choice between two IUDs with equal frames measuring 32 × 32 mm-the LNG-IUS 52 mg or a copper-releasing IUD. The women were followed for 1 year., Participants/material, Setting, Methods: The LNG-IUS was chosen by 113 women (68.5%) and the copper IUD by 52 (31.5%). Prior to insertion the women were interviewed concerning their menstrual characteristics and uterine cavity size was measured by 2-D ultrasonography. After insertion the women kept daily records of bleeding and pain for two reference periods of 90 days during the first year (Months 1-3 and 10-12). The correlation between uterine cavity measurements and numbers of days of bleeding/spotting and pain during the reference periods was analysed. Continuation rates were assessed and reasons for discontinuation as well as the effects of baseline participant characteristics on outcomes were analysed in regression models., Main Results and the Role of Chance: Both uterine cavity size and baseline menstrual characteristics prior to IUD insertion predicted the numbers of days of bleeding/spotting and pain in LNG-IUS users. Women with small uterine cavity dimensions reported less bleeding/spotting in both reference periods and less pain in the second reference period compared with women with larger dimensions. Baseline scanty spontaneous menstrual bleeding prior to LNG-IUS use (OR 9.4, 95% CI 1.7-51.8, P = 0.01) and smoking (OR 7.8, 95% CI 1.8-33.8, P = 0.006) predicted amenorrhoea in the second reference period. Women with baseline dysmenorrhoea reported more pain with both IUDs. Continuation rates and reasons for discontinuation were similar with both IUDs., Limitations, Reasons for Caution: No sample size could be calculated to estimate the power as this was a pilot study. As the majority of women chose the LNG-IUS we did not achieve our initial aim of equally sized IUD groups and thus the size of the copper IUD group may have been insufficient to detect differences., Wider Implications of the Findings: These data further encourage promotion of intrauterine contraception among nulligravid women. Routine use of ultrasonography to assess uterine cavity dimensions prior to IUD insertion is not indicated., Study Funding/competing Interests: Supported by Helsinki University Central Hospital research funds, the Swedish Cultural Foundation in Finland and Finska Läkaresällskapet, who provided funds for J.K. O.H. serves on advisory boards for Bayer Healthcare, Gedeon Richter and MSD Finland (part of Merck & Co. Inc.) and has designed educational events with these companies. S.S. has lectured in educational events at Bayer and MSD Finland (part of Merck & Co. Inc.) and is a member of the Advisory Board for Contraception at MSD Finland. The other authors have no conflicts of interest to declare., Trial Registration Number: www.clinicaltrials.gov, NCT01685164., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to assess the presence of ovarian cysts in women using a new low-dose levonorgestrel-releasing intrauterine contraceptive system (LNG-IUS 13.5mg [total content])., Study Design: A Phase 3 study assessed LNG-IUS 13.5mg use in healthy women with regular menstrual cycles who requested contraception. Transvaginal ultrasonography was performed at screening, baseline, and 3, 6, 9, 12, 18, 24, 30, and 36 months after placement., Results: A total of 1432 women, mean age 27.2±4.8 years, were studied. A total of 10,446 transvaginal ultrasound examinations were performed over 3 years. Ovarian cysts were present in 1.6, 1.1, 2.3, 2.1, 2.4, 2.0, 2.1, 2.2, 1.9, and 2.1% of participants at screening, baseline, and Months 3, 6, 9, 12, 18, 24, 30, and 36, respectively. One hundred first-time ovarian cysts were identified from baseline through Month 9. The size distribution through Month 12 was ≤30 mm (13%), >30 to ≤50 mm (74%), >50 to ≤80 mm (11%), and >80 mm (0%). The overall persistence of ovarian cysts from one examination to the next in Year 1 was 12% (11/90 with follow-up). Cyst persistence was 36% from baseline to 3 months, 13% from 3 to 6 months, 10% from 6 to 9 months, and 0% from 9 to 12 months. The likelihood of cyst persistence increased for cysts >50mm (36%) as compared to those ≤50 mm (8%)., Conclusion: Ovarian cysts were present in 1.6% of women at screening, 2.0 to 2.4% of LNG-IUS 13.5mg users during Year 1, and 1.9 to 2.1% during Years 2 and 3. The majority were >30 to ≤50 mm in size. The small and diminishing number of persistent cysts-decreasing to 0% from 9 to 12 months-suggests that they were functional in nature., Implications: Transvaginal ultrasound follow-up of women during a 3-year clinical trial of LNG-IUS 13.5mg showed that ovarian cysts were present in 1.6% of participants at screening and 1.1-2.4% at each subsequent visit. Eighty-eight percent were ≤5cm, with none >8cm. No ovarian cysts persisted beyond Month 9, suggesting a functional etiology., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy and safety of the levonorgestrel-releasing intrauterine device (LNG-IUD) with dydrogesterone applied for the same duration in patients having endometrial hyperplasia (EH) without atypia., Materials and Methods: One hundred thirty eight women aged between 30 and 50 years with abnormal uterine bleeding and diagnosed as EH by transvaginal ultrasound were randomized to receive either LNG-IUD or dydrogesterone for 6 months. Primary outcome measures were regression of hyperplasia after 6 months of therapy. Secondary outcome measures were occurrence of side effects during treatment or recurrence of hyperplasia during follow-up period., Results: After 6 months of treatment, regression of EH occurs in 96% of women in the levonorgestrel-releasing intrauterine system (LNG-IUS) group versus 80% of women in the oral group (P < .001). Adverse effects were relatively common with minimal differences between the 2 groups. Intermenstrual vaginal spotting and amenorrhea were more common in the LNG-IUD group (P value .01 and .0001). Patient satisfaction was significantly higher in the LNG-IUS group (P value .0001). Hysterectomy rates were lower in the LNG-IUS group than in the oral group (P = .001). Recurrence rate was 0% in the LNG-IUD group compared to 12.5% in the oral group., Conclusion: In management of EH without atypia, LNG-IUS achieves a higher regression and a lower hysterectomy rate than oral progesterone and could be used as a first-line therapy., (© The Author(s) 2014.)

Objective: The aim of the study is to assess the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) on the tamoxifen-induced endometrial lesions in breast cancer patients., Methods: PubMed and EMBASE databases were searched for eligible studies. Odds ratios were obtained to estimate the association between the LNG-IUS and tamoxifen-induced endometrial lesions. The fixed effects or random-effects model was used to combine data depending on heterogeneity., Results: With three eligible randomized clinical trials involving 359 patients, this analysis demonstrated tamoxifen-treated breast cancer patients using the LNG-IUS derived benefit from de novo polyps prevention (P < 0.0001, OR 0.18, 95% CI: 0.08-0.42). However, the LNG-IUS only showed a trend of maintaining endometrial proliferation or secretory status (P = 0.05, OR 0.36, 95% CI 0.13-1.02) and no statistical difference in atrophic or inactive changes (P = 0.13, OR 0.24, 95% CI 0.04-1.53) or endometrial hyperplasia without atypia (P = 0.08, OR 0.20, 95% CI 0.04-1.18). The LNG-IUS didn't have an increased incidence in breast cancer recurrence (P = 0.28, OR 1.75, 95% CI: 0.64-4.80) and cancer-induced death (P = 0.71, OR 1.22, 95% CI: 0.42-3.52). Bleeding in the treatment group was statistically more frequent than that in the control group (OR 6.20, 95% CI: 2.99-12.85, P < 0.00001)., Conclusions: This analysis verifies the efficacy of the LNG-IUS in preventing tamoxifen-induced polyps. The LNG-IUS didn't have an increased incidence in breast cancer recurrence and cancer-induced death. Long-term, large randomized studies of the LNG-IUS will be necessary to determine the benefit and risk in tamoxifen-treated breast cancer patients.

Study Question: What are the regression and hysterectomy rates for women treated with the levonorgestrel-releasing intrauterine system (LNG-IUS) compared with oral progestogens for endometrial hyperplasia (EH)?, Summary Answer: The LNG-IUS achieves higher regression and lower hysterectomy rates than oral progestogens in the treatment of complex and atypical hyperplasia., What Is Known Already: The LNG-IUS and oral progestogens are both equally used to treat women with EH. There is uncertainty about whether the LNG-IUS is a better therapy for EH., Study Design, Size, Duration: This comparative cohort study included 344 women recruited from August 1998 until December 2010., Participants/materials, Setting, Methods: Women with complex non-atypical or atypical EH were treated with the LNG-IUS (n = 250) or oral progestogens (n = 94) in a tertiary referral hospital. We evaluated the proportion of women who regressed or underwent hysterectomy after treatment with the LNG-IUS compared with oral progestogens by logistic regression adjusting for confounding. The time from diagnosis to regression was explored through a survival analysis., Main Results and the Role of Chance: The follow-up rate was 95.3%. The mean length of follow-up in the two groups was 66.9 ± SD 35.1 months for the LNG-IUS and 87.2 ± SD 45.5 months for the oral progestogen group. Regression of hyperplasia was achieved in 94.8% (237/250) of patients with the LNG-IUS compared with 84.0% (79/94) of patients treated with oral progestogens (adjusted odds ratio (OR) = 3.04, 95% CI 1.36-6.79, P = 0.001). Hysterectomy rates were lower in the LNG-IUS group during follow-up (22.1, 55/250 versus 37.2%, 35/94, adjusted OR = 0.48, 95% CI 0.28-0.81, P < 0.004). Endometrial cancer was diagnosed in 8 (33%) women who had hysterectomy because of a failure to regress to normal histology during follow-up (n = 24)., Limitations, Reasons for Caution: The observational design cannot exclude residual confounding from unmeasured variables., Wider Implications of the Findings: In treating EH, LNG-IUS achieves higher regression rates and lower hysterectomy rates than oral progestogens and should be the first-line therapy. Failure to achieve regression carries a high risk of underlying endometrial cancer and hysterectomy is advised.

This study was designed to evaluate the feasibility and effectiveness of hysteroscopy in the management of symptoms related to endometrial polyps and submucous leiomyomas in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). Twenty-three LNG-IUS users presenting with endometrial polyps and/or submucous leiomyomas and irregular uterine bleeding were recruited for hysteroscopic examination and surgery. Intrauterine pathology was investigated and treated by hysteroscopic resection with the LNG-IUS in situ, and the effect of the procedure on symptoms was evaluated after three to six months. Intrauterine pathology was successfully resected by hysteroscopy in 23 (100.0%) out of 23 cases. Following hysteroscopy, 18 (78.3%) women reported amenorrhea, one (4.3%) regular spotting, three (13.0%) irregular spotting and one (4.3%) patient resumed normal menstrual cycle. We conclude that 19 (82.6%) patients were postoperatively asymptomatic. All procedures were uncomplicated and 4 (17.4%) were carried out without general anesthesia as office procedures. Endometrial polyps and submucous leiomyomas can develop in LNG-IUS users, and this can cause irregular uterine bleeding. Hysteroscopic resection of these pathologies is a feasible method in the clinical management of symptoms. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of levonorgestrel 52 mg intrauterine system for intermenstrual bleeding in patients with previous cesarean delivery scar defects (PCDSs). Methods: The medical records of 28 consecutive patients with previous cesarean delivery scar defect and intermenstrual bleeding who had undergone conservative treatment with levonorgestrel 52 mg intrauterine system were reviewed. The efficacy of treatment and frequency of adverse events were measured retrospectively. Results: After 1 year of treatment, 22 patients (78.6%) reported an improvement in symptoms. The mean duration of menstruation were 18 and 5 days before and after treatment, respectively. No uterine perforations or pelvic inflammatory diseases occurred during or after the insertion procedures. Eighteen (64.3%) patients did not experience any adverse events, and the patients with adverse events reported that they could be managed by adjusting their medications or observation. Conclusion: Levonorgestrel intrauterine system may have a role in the safe and effective management of intermenstrual spotting in patients with PCDSs. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to assess whether the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) were lower among women using the progestin-only pill (POP) or levonorgestrel-releasing intrauterine system (LNG-IUS) and similar to the decrease observed in combined oral contraceptive (COC) pill users.Methods: This retrospective study comprised 565 hormonal contraceptive users (COC, POP, LNG-IUS or contraceptive vaginal ring) and 983 non-hormonal contraceptive users, who were seen in two Danish fertility assessment and counselling clinics between 2015 and 2019. Adjusted multiple regression analysis was used to examine the differences in AMH and AFC between hormonal and non-hormonal contraceptive users.Results: Compared with non-hormonal contraceptive users, AMH was 31.1% lower among COC users [95% confidence interval (CI) -39.6%, -25.9%; p < 0.001], 35.6% lower among POP users (95% CI -49.0%, -18.6%; p < 0.001) and 17.1% lower among LNG-IUS users (95% CI -31.4%, 0.002%; p = 0.052); no significant differences were seen among vaginal ring users. Compared with non-hormonal contraceptive users, AFC was 31.3% lower among COC users (95% CI -35.0%, -25.3%; p < 0.001) and 29.7% lower among POP users (-39.1%, -17.9%; p < 0.001); no significant differences were seen among LNG-IUS or vaginal ring users. Ovarian volume was more than 50% reduced among COC and vaginal ring users (p < 0.001) but was unchanged among POP and LNG-IUS users.Conclusion: Assessment of ovarian reserve markers among users of all types of hormonal contraception should be interpreted cautiously and the type of contraceptive method considered. [ABSTRACT FROM AUTHOR]

Dustin J Costescu Department of Obstetrics and Gynaecology, McMaster University, Hamilton, ON, Canada Abstract: Unintended pregnancy is a significant global problem. In 2008, there were over 100 million unplanned pregnancies worldwide, representing approximately 41% of global conceptions. Family planning strategies in many countries are shifting from increasing the uptake of contraception among nonusers to increasing the uptake of the most effective methods among users of less effective methods. One of the most effective and acceptable methods of contraception is the levonorgestrel-releasing intrauterine system (LNG IUS); however, its uptake varies widely by country. This article reviews the currently available LNG IUSs, the rationale for increasing uptake of these methods, and evidence regarding safety, and discusses counseling strategies to best inform women about this option for contraception. Keywords: LNG IUS, long-acting contraception, intrauterine contraception, levonorgestrel, contraception, family planning

Background: Dysfunctional uterine bleeding (DUB) is one of the commonest condition for which patient seeks out medical consultation. The prevalence increases with the increase of age peaking before menopause. Objectives: The aim of this work is to evaluate the effect of this new form of levonorgestrel-releasing IUD on the treatment of patients with abnormal uterine bleeding. Patients and Methods: A prospective age-specific comparative analysis of 61 peri-menopausal women presented with dysfunctional uterine bleeding who constituted the study group. They underwent hysteroscopy and endometrial sampling during an 18 months period from June 2014 to January 2016 at Ain Shams University Materity Hospital. Prior to metraplant-E application, all the patients in this study were in the age of 25-58 years old. Results: The role of Metraplant-E in the treatment of abnormal uterine bleeding (AUB) was evaluated. Sixtyone women with failed attempt(s) of medical treatment unwilling or unfit for hysterectomy were treated with Metaplant-E. Menstrual blood loss was assessed by pictoral bleeding assessment chart (PBAC), bleeding index (B.I) and total bleeding score (T.B.S/month). The bleeding patterns in the form of the mean menstrual blood loss estimated by bleeding index and the mean menstrual loss estimated by the total bleeding score/month and PBAC decreased significantly (p = 0.001). The quality of life scale (Likert scale) improved significantly (p = 0.001). All 15 cases who had endometrial sampling demonstrated progestational effect on histo-pathological examination. Conclusion: Metraplant-E was found to be effective in managing dysfunctional menorrhagia on both clinical and histopathological levels. [ABSTRACT FROM AUTHOR]

Uterine fibroids are considered to be the most frequently occurring tumours in females. The majority of fibroids do not require any treatment. When symptomatic, the major ailments include abnormal uterine bleeding, painful menstruation, pelvic pressure or pain, urinary problems, constipation, infertility, and recurrent pregnancy loss. Surgery remains a mainstay of symptomatic uterine fibroids therapy; however, minimally-invasive techniques and pharmacological management have become more available. The levonorgestrel intrauterine system (LNG-IUS) is a T-shaped device with a vertical stem containing a reservoir of levonorgestrel and is widely known for its contraception effect. Moreover, the non-contraceptive benefits of the LNG-IUS have been previously confirmed by numerous studies. LNG-IUS causes reduction of the duration and the amount of menstrual bleeding, with minimal side effects due to release of hormones at the targeted organ. Currently, results from systematic reviews show that LNG-IUS may be an effective and safe treatment for symptomatic uterine fibroids in premenopausal women. However, further studies are required to consolidate the usage of LNG-IUS in the treatment of symptomatic uterine fibroids. [ABSTRACT FROM AUTHOR]

The concept of using a frameless intrauterine device (IUD) instead of the conventional plastic framed IUD is not new. Frameless copper IUDs have been available since the late 1990s. They rely on an anchoring system to retain in the uterine cavity. The clinical experience with these IUDs suggests that frameless IUDs fit better as they are thin and, therefore, do not disturb or irritate the uterus. High tolerance and continuation rates have been achieved as complaints of pain are virtually nonexistent and the impact on menstrual blood loss is minimal. Conventional levonorgestrel-releasing intrauterine systems (LNG-IUSs) are very popular as they significantly reduce menstrual bleeding and provide highly effective contraception. However, continuation of use remains problematic, particularly in young users. Total or partial expulsion and displacement of the LNG-IUS also occur too often due to spatial incompatibility within a small uterine cavity, as strong uterine contractions originate, attempting to get rid of the bothersome IUD/ IUS. If not expelled, embedment ensues, often leading to chronic pain and early removal of the IUD/IUS. Several studies conducted recently have requested attention to the relationship between the LNG-IUS and the endometrial cavity. Some authors have proposed to measure the cavity width prior to inserting an IUD, as many uterine cavities are much smaller than the currently existing LNG-IUSs. A frameless fibrous drug delivery system fits, in principle, in all uterine cavities and may therefore be preferable to framed drug delivery systems. This review examines the clinical performance, acceptability, and potential of the frameless LNG-IUS (FibroPlant®) when used for contraception, treatment of heavy menstrual bleeding, dysmenorrhea, and endometrial suppression in women using estrogen replacement therapy, endometrial hyperplasia, and other gynecological conditions. The review concludes that FibroPlant LNG-IUS offers unique advantages in reducing side effects. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our study was to compare acceptability of the copper intrauterine device (Cu-IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) among women living with the human immunodeficiency virus (HIV).Methods: We randomly assigned 703 HIV-positive women in Uganda to receive either a Cu-IUD or an LNG-IUS and followed them for at least one year. During the follow-up visits, face-to-face interviews were conducted with the women and acceptability of the Cu-IUD or LNG-IUS was assessed, using a Likert scale, at one, three, six and twelve months. At the final follow-up visit, women were also assessed for satisfaction with either method.Results: Between 9 September 2013 and 31 December 2014, 703 women were recruited and assigned as follows: 349 to a Cu-IUD group and 354 to an LNG-IUS group. Acceptability decreased from 94.3% at one month to 87.7% at 12 months in the Cu-IUD group and from 96.3% at one month to 86.7% at 12 months in the LNG-IUS group (p = 0.97). Satisfaction with intrauterine contraception was reported by 83.7% (283/338) in the Cu-IUD group and by 90.4% (302/334) in the LNG-IUS group (p = 0.50).Conclusions: There was no significant difference in acceptability between the LNG-IUS and Cu-IUD among HIV-positive women. Satisfaction rates were high and similar in the two groups. Both the Cu-IUD and LNG-IUS are acceptable forms of contraception for HIV-positive women and should be made available to women in HIV care to increase their contraceptive method options.Clinical Trial Registration: The trial is registered at the Pan African Clinical Trials Registry (PACTR 201308000561212). [ABSTRACT FROM AUTHOR]