Levonorgestrel-releasing Intrauterine System Research Articles

Levonorgestrel-Releasing Intrauterine System as a Contraceptive Method in Nulliparous Women: A Systematic Review.

The aim of this review was to summarize the available evidence about the use of levonorgestrel-releasing intrauterine system (LNG-IUS) as a contraceptive method in nulliparous women. For this purpose, studies evaluating the efficacy, safety, bleeding pattern, satisfaction and discontinuation of the levonorgestrel-releasing intrauterine system in nulliparous women were analyzed. Only original research articles published in English between 1990–27th March 2020 were considered eligible. Reviews, book chapters, case studies, conference papers, opinions, editorials and letters were excluded. The systematic literature search of PubMed/MEDLINE, Scopus, Embase and Cochrane Library databases identified 816 articles, 23 of which were analyzed. The available evidence indicates that LNG-IUS is an effective and safe contraceptive method for nulliparous women that achieves high levels of satisfaction among patients. Moreover, nulliparous women seem to experience fewer expulsions than parous ones. Bleeding pattern is acceptable for the majority of patients, and bleeding disorders mainly occur in the first months after the insertion. More in-depth, long-term prospective studies are needed in this patient group to determine risk factors for the occurrence of side effects and associated discontinuations, which should not, however, delay the wider use of the method in this group, given the number of advantages.

Adjuvant therapy of Chinese herbal medicine for the treatment of adenomyosis: A protocol for systematic review.

Background:Adenomyosis is benign gynecologic condition with complex etiologies. Common symptoms associated with adenomyosis (AM) include menorrhagia, dysmenorrhea, chronic pelvic pain, metrorrhagia, and dyspareunia. Although Chinese herbal medicine (CHM) has often been utilized for managing AM in clinical practice in China, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a systematic review to assess the effectiveness and safety of CHM combined with Levonorgestrel-releasing intrauterine system for AM.Methods:The following 7 databases will be searched from the publishment to December 2019: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Digital Periodicals (WAN FANG), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP). The primary outcomes will be relief in pain and uterine bleeding. The secondary outcomes include the adverse effects, CA125 variation in peripheral blood, reduction in uterine volume, and endometrial thickness. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis will be conducted. We will use risk ratio with 95% confidence interval for dichotomous data and the mean difference for continuous data.Results:This study will provide the latest analysis of the currently available evidence for the efficacy of the adjuvant therapy of CHM for the treatment of AM.Registration number:OSF (DOI 10.17605/OSF.IO/A2GHY)Ethics and dissemination:No ethical issues are required. The findings will be published in a peer-reviewed scientific journal.

Free-of-charge long-acting reversible contraception: two-year discontinuation, its risk factors, and reasons

Since 2013, the residents of the city of Vantaa, Finland, have been offered their first long-acting reversible contraceptive method (levonorgestrel-releasing intrauterine system, implant, and copper intrauterine device) free of charge. The primary aim of this study was to assess the 2-year cumulative discontinuation rates of long-acting reversible contraceptive methods when provided free of charge for first-time users in a real-world setting. Additional aims were to describe factors associated with discontinuation and to evaluate the reasons for discontinuation. This is a retrospective register-based cohort study of 2026 nonsterilized women aged 15 to 44 years, who initiated a free-of-charge long-acting contraceptive method in 2013-2014 in the city of Vantaa. Removals within 2 years after method initiation and reasons for discontinuation were obtained from electronic health records and from national registers. We calculated the 2-year cumulative incidence rates of discontinuation with 95% confidence intervals for each method. Furthermore, we assessed crude and adjusted incidence rate ratios of discontinuation with 95% confidence interval by Poisson regression models comparing implants and copper intrauterine device with levonorgestrel-releasing intrauterine systems. During the 2 -year follow-up, 514 women discontinued, yielding a cumulative discontinuation rate of 28.3 per 100 women-years (95% confidence interval, 26.2-30.4). Among the 1199 women who initiated the levonorgestrel-releasing intrauterine system, the cumulative discontinuation rate was 24.2 per 100 women-years (95% confidence interval, 21.7-26.9); among the 642 implant users, 33.3 per 100 women-years (95% confidence interval, 29.5-37.4); and among the 185 copper intrauterine device users, 37.8 per 100 women-years (95% confidence interval, 31.0-45.7). Compared with women aged 30 to 44 years, women aged 15 to 19 years (adjusted incidence rate ratio, 1.58; 95% confidence interval, 1.17-2.14) and 20 to 29 years (adjusted incidence rate ratio, 1.35; 95% confidence interval, 1.11-1.63) were more likely to discontinue. We observed a higher discontinuation rate in women who had given birth within the previous year (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.13-1.65), spoke a native language other than Finnish or Swedish (adjusted incidence rate ratio, 1.31; 95% confidence interval, 1.06-1.63), and had a history of a sexually transmitted infection (adjusted incidence rate ratio, 1.62; 95% confidence interval, 1.07-2.46). No association was found in marital status, overall parity, history of induced abortion, socioeconomic status, education level, or smoking status. The most common reason for discontinuation was bleeding disturbances, reported by 21% of women who discontinued the levonorgestrel-releasing intrauterine system, by 71% who discontinued the implant, and by 41% who discontinued the copper intrauterine device. One in 4 women who discontinued the copper intrauterine device reported heavy menstrual bleeding, whereas only 1% who discontinued the levonorgestrel-releasing intrauterine system and none who discontinued implants reported this reason. Abdominal pain was the reported reason for discontinuation in 20% of both intrauterine device users and in only 2% who discontinued implants. At 2 years, the use of implants and copper intrauterine devices was more likely to be discontinued than that of the levonorgestrel-releasing intrauterine system. Women younger than 30 years and those who gave birth in the preceding year, spoke a native language other than Finnish or Swedish, or had a history of sexually transmitted infections were more likely to discontinue. The levonorgestrel-releasing intrauterine system was least likely to be removed owing to bleeding disturbances.

Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

The effect of a levonorgestrel-releasing intrauterine device on female sexual function

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.

Indications and reasons for discontinuing the levonorgestrel-releasing intrauterine system (LNG-IUS)

Abstract Objectives: to identify the main indications and reasons for discontinuing the use of the Levonorgestrel-Releasing Intrauterine System (LNG-IUS). Methods: a cross-sectional study was carried out from medical records of 327 women who used the LNG-IUS 52mg between January 2011 and December 2016 at a public hospital in the Northeast of Brazil. Results: the main indications for the use of the LNG-IUS were: contraception (32.7%), myoma/metrorrhagia (28.7%) and endometriosis/pelvic pain (22.3%). Of the 327 women, 68 (20.8%) had discontinued using the device. The most frequent reasons for discontinuation were: expulsion (9.2%), LNG-IUS expiration (3.7%), bleeding (2.4%) and pain (1.5%). Most patients had no difficulty in the insertion and did not require anesthesia/sedation. Among the 30 women who expelled the device, 17 (56.7%) had used it for metrorrhagia and myoma, 8 (26.7%) for contraception, and 5 (16.6%) for endometriosis/pelvic pain. Conclusions: the LNG-IUS is a well-accepted contraceptive method, with therapeutic applications for some gynecological conditions and a low expulsion rate.

Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users.

Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users.

Use of a levonorgestrel 52-mg intrauterine system in the control of abnormal uterine bleeding in women with inherited bleeding disorders

ObjectiveTo evaluate the efficacy of a levonorgestrel 52-mg intrauterine system (LNG 52-mg IUS) in controlling abnormal uterine bleeding and improving quality of life in women with inherited bleeding disorders. Study designWe assessed 20 participants laboratory diagnosed with inherited bleeding disorders, who presented with abnormal uterine bleeding and were registered in a Central Blood Center. The primary outcomes were menstrual bleeding volume and quality of life before and after LNG 52-mg IUS placement. We used the Pictorial Blood Loss Assessment Chart (PBAC) score for measuring menstrual bleeding and the Short Form-36 Health Survey to assess quality of life before and after LNG 52-mg IUS placement. We also conducted blood tests to evaluate the hematimetric level. Follow-up visits were conducted at 1, 3, 6, and 12 months after LNG 52-mg IUS placement. Statistical analyses were performed using the Friedman non-parametric test. ResultsThe use of LNG 52-mg IUS reduced uterine bleeding in women with inherited bleeding disorders. The median PBAC score was higher before LNG 52-mg IUS placement than at 3, 6, and 12 months after placement (p < 0.001). The amenorrhea rate was 70% after 12 months. There was an improvement in all eight parameters of quality of life (p < 0.001). The mean hemoglobin, ferritin, and serum iron levels were also higher at 12 months than before LNG 52-mg IUS placement. ConclusionLNG 52-mg IUS placement can effectively control abnormal uterine bleeding in women with inherited bleeding disorders and consequently improve their quality of life. ImplicationsThe results from our study suggest that women with inherited bleeding disorders who present with heavy menstrual bleeding can benefit from the use of a levonorgestrel-releasing intrauterine system similar to women without bleeding disorders.

Prevention of Benign Endometrial Polyp Recurrence Using a Levonorgestrel-releasing Intrauterine System in Premenopausal Patients: A Retrospective Cohort Study

To evaluate the levonorgestrel-releasing intrauterine system (LNG-IUS) to prevent the recurrence of endometrial polyps (EPs) after hysteroscopic polypectomies in premenopausal female patients. A retrospective cohort study. A tertiary-care women's hospital. A total of 451 premenopausal female patients underwent hysteroscopic polypectomies between January 1, 2016, and December 31, 2017. Treatment with LNG-IUS after hysteroscopic polypectomies. After the hysteroscopic polypectomies and placement of LNG-IUS, transvaginal ultrasounds were performed every 6 months to measure the recurrence of EPs. Overall, 5 (3.47%) of 144 patients in the LNG-IUS cohort and 49 (15.96%) of 307 patients in the control cohort experienced EP recurrence within the follow-up period of up to 3 years. The recurrence exhibited a strongly negative correlation when LNG-IUS was inserted (relative risk, 0.218; 95% confidence interval, 0.089-0.535; p <.05), but this did not significantly correlate with age, polyp size, number of polyps, previous history of polypectomy, and abnormal uterine bleeding. For the LNG-IUS and control cohorts, the recurrence in the first postoperative year was 1.39% and 6.19%, respectively, and 5.41% and 19.23% in the second postoperative year, respectively. LNG-IUS reduces the recurrence of postoperative EPs in premenopausal patients.

Current and Future Medical Therapies for Adenomyosis.

There is no approved medical therapy for adenomyosis and limited evidence to guide treatments in part due to the complexity of nonhistologic diagnosis and the prevalence of concomitant gynecologic conditions. Most available evidence focuses on the treatment of heavy menstrual bleeding, painful menses, and pelvic pain. Data evaluating fertility outcomes, sexual function, and quality of life following treatment are lacking. Additionally, there is no disease-specific measure of quality of life for adenomyosis. The levonorgestrel-releasing intrauterine system appears to be the most effective first-line therapy based on efficacy compared with oral agents, maintenance of steady-state hormonal levels, and contraceptive benefit. In areas where it is marketed, the progestin dienogest appears superior to combined oral contraceptives. Long-acting gonadotropin-releasing hormone agonists are effective and should be considered second-line therapy but are limited by hypogonadal effects. Additional data regarding oral gonadotropin-releasing hormone antagonists are required. While aromatase inhibitors demonstrate improvement in heavy menstrual bleeding and pelvic pain, further research is needed to determine their role in the management of adenomyosis. Progesterone receptor modulators may have a role for this disease if released again to market with appropriate safety parameters. Finally, modulation of prolactin and/or oxytocin may provide novel nonsteroidal treatment options.

Effects of LNG-IUS on sexual function and sexual quality in women of childbearing age

Objective: To investigate the effects of levonorgestrel releasing intrauterine system (LNG-IUS) on sexual function and sexual quality in women of childbearing age. Methods: A total of 203 healthy women who were using IUD for long-term contraception were enrolled in the study. Among them, 130 were placed LNG-IUS as the study group and 73 were placed the copper intrauterine devices (Cu-IUDs) as the control group. The two groups were further divided into three subgroups by age. The basic information and questionnaires were adopted before and 2 years after using IUDs, including age, the time of using IUD, side-effects after using IUD, frequency and satisfaction of sex after using IUD. The Female Sexual Function Index (FSFI) was evaluated on 2 years after. Results: In the 30-39 age subgroup, the frequency of sex was significantly decreased after using LNG-IUS (P<0.05). Rests of the subgroup shows no significantly different in the frequency of sex (P>0.05). The sexual satisfaction in all subgroups also shows no significantly different before and after using IUDs (P>0.05). There was no significant difference in the individual score and total scores of FSFI between the study group and control group (P>0.05). Conclusion: The LNG-IUS has no adverse effects on female sexual function and sexual quality in the reproductive age.

Differential Effects of the Hormonal and Copper Intrauterine Device on the Endometrial Transcriptome

The contraceptive effectiveness of intrauterine devices (IUDs) has been attributed in part to a foreign body reaction in the endometrium. We performed this study to better understand mechanisms of action of contraceptives of by studying their effects on endometrial and cervical transcriptomes. We collected endometrial and cervical biopsies from women using the levonorgestrel-releasing intrauterine system (LNG-IUS, n = 11), copper intrauterine device (cu-IUD, n = 13) or levonorgestrel-containing combined oral contraceptives (COC, n = 12), and from women not using contraceptives (control group, n = 11). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. In endometrial samples from cu-IUD users, there were no genes with statistically significant differential expression compared to controls. In LNG-IUS users, 2509 genes were differentially expressed and mapped predominantly onto immune and inflammatory pathways. The cervical samples showed no statistically significant differential gene expression compared to controls. Hormonal and copper IUDs have significantly different effects on the endometrial transcriptome, with the LNG-IUS transcriptome showing pronounced inflammation and immune activation compared to controls whereas the cu-IUD transcriptome was indistinguishable from luteal phase endometrium. These findings argue against a foreign body reaction as a common mechanism of action of IUDs.

Benefits of vaginal dinoprostone administration prior to levonorgestrel-releasing intrauterine system insertion in women delivered only by elective cesarean section: a randomized double-blinded clinical trial.

This study aimed at investigating the efficacy and safety of dinoprostone 3mg vaginally prior to levonorgestrel-releasing intrauterine system (LNG-IUS) insertion in women undergoing elective cesarean delivery (CD). We conducted a prospective, randomized, double-blinded, placebo-controlled trial at family planning clinic of Cairo University hospitals from August 2019 to January 2020. We included 200 women aged ≥ 18years who previously delivered by elective CD willing to receive LNG-IUS. Women were randomly assigned with a 1:1 allocation ratio to receive 3mg vaginal dinoprostone or placebo tablets two hours before LNG-IUS insertion. Our main outcomes were patient-reported pain during insertion and 30min post-procedure, ease of insertion, satisfaction, duration of insertion, and different side effects. Patient-perceived pain during LNG-IUS insertion was significantly reduced in dinoprostone compared to placebo (4.1 ± 1.7 vs 6.4 ± 1.3; p < 0.001). Dinoprostone reduced pain scores 30min post-procedure compared to placebo, but the difference was not statistically significant (3.5 ± 1.1 vs 3.7 ± 1.6; p = 0.25). Satisfaction score was higher in dinoprostone compared to placebo (7.9 ± 1.0 vs 5.9 ± 0.8; p < 0.001). The insertion was significantly easier and shorter in dinoprostone than placebo (3.9 ± 1.1 vs 5.9 ± 1.1; p < 0.001) and (5.6 ± 0.9 vs 7.2 ± 0.8; p < 0.001), respectively. Adverse events were not significantly different between both groups. Dinoprostone administration 2h before LNG-IUS insertion in women delivered by elective CD effectively reduced pain during insertion and 30min post-procedure. Women received dinoprostone had easier and shorter insertion and were more satisfied with tolerable side effects.

Efficiency of the combination of transdermal estrogens and a hormone-releasing intrauterine system for the correction of menopausal symptoms

Hypothesis/aims of study. The aim of this study was to assess the efficiency of Mirena (levonorgestrel-releasing intrauterine system) combined with EstroGel (17-estradiol transdermal gel) being applied in the test group of peri- and postmenopausal women as menopausal hormonal therapy.&#x0D; Study design, materials and methods. The study involved 62 patients aged 42 to 55 years. The main group included 33 women who were prescribed Mirena in combination with EstroGel. The control group consisted of 29 women who were prescribed a combined two-phase tablet preparation containing micronized 17-estradiol as an estrogen component and dydrogesterone as a gestagen component. The condition of the patients was evaluated at the beginning of therapy and after 3, 6 and 12 months.&#x0D; Results. During therapy, patients in the main group decreased climacteric symptoms and improved lipid profile and blood biochemical parameters characterizing the hepatobiliary system. Patients in the control group had a comparable decrease in menopausal symptoms; however, there were changes in biochemical parameters, such as hypertriglyceridemia and a significant increase in bilirubin and transaminases, which required discontinuation of therapy. All the patients using Mirena in combination with EstroGel demonstrated good tolerability, efficiency of the therapy and no significant symptoms requiring its withdrawal. During the menopausal hormonal therapy, there were no cases of relapse of endometrial hyperplasia, growth of myomatous nodes and an increase in endometriosis prevalence. Patients in the control group during the first three months of therapy noted acyclic spotting, breast engorgement and tenderness, headaches, and exacerbation of cholelithiasis, which resulted in decreased adherence to therapy.&#x0D; Conclusion. The use of estrogen transdermally in combination with the intrauterine administration of levonorgestrel is an effective and safe method that helps to relieve menopausal symptoms and to improve the health and quality of life of women with extragenital pathology, endometrial and mammary gland hyperplastic processes, endometriosis, and menometrorrhagia.

Consecutive Use of the 52 mg Levonorgestrel-releasing Intrauterine System: Variations in Bleeding Patterns.

Changes in bleeding patterns could influence the decisions of healthcare professionals to change the levonorgestrel-releasing intrauterine system (LNG-IUS) before 7 years of use, the recommended period of extended use. We evaluated changes in the bleeding patterns of users of the 52 mg LNG-IUS at the end of use of the first (IUS-1) and during the second device (IUS-2) use. We performed an audit of the medical records of all women who used two consecutive LNG-IUSs at the Family Planning clinic. We evaluated the sociodemographic/gynecological variables, the length of use, and the bleeding patterns reported in the reference periods of 90 days before removal of the IUS-1 and at the last return in use of IUS-2. We used the McNemar test to compare bleeding patterns. Statistical significance was established at p < 0.05. We evaluated 301 women aged (mean ± SD) 32 (±6.1) years, with lengths of use of 68.9 (±16.8) and 20.3 (±16.7) months for the IUS-1 and IUS-2, respectively. No pregnancies were reported. Bleeding patterns varied significantly among women who used the IUS-2 for ≥ 7 months to 6 years when compared the bleeding patterns reported in IUS-1 use. Eighty-nine out of 221 (40%) women maintained amenorrhea and infrequent bleeding; 66 (30%) evolved to bleeding patterns with light flow, and 66 (30%) maintained or evolved to heavy flow patterns (p = 0.012). No differences were observed among the 80 women with ≤ 6 months of use. Changes in bleeding patterns occur during the use of LNG-IUS and should not be decisive for the early replacement of the device.

Levonorgestrel Intrauterine System Effects versus Copper Intrauterine Device on Changing Of Menstruation and Uterine Artery Doppler

Background: The most effective methods for birth control are the long-acting reversible contraceptives LARCs include Paragard IUD in silver, Mirena IUD in hormonal (progesterone) and hormonal contraceptive implant. The intrauterine levonorgestrel-releasing system (LNG-IUS) and the intrauterine copper unit (Cu-IUD) influenced changing of menstruation and uterine artery Doppler indices Aim of the work: Comparison of the effects of copper intrauterine device (Cu-IUD) and an intrauterine levonorgestrel releasing system (LNG-IUS) on changing of menstruation and Doppler indices of uterine arteries. Methods: This was RCT was completed between February 2017 to January 2020 at the Obstetrics and Gynecology department, Tanta University hospitals. There were two group first group A :LNG-IUS (N=200) and second group B CuIUD (N=200), they were randomly assigned to 400 multiparous women preferring intrauterine contraception., the UA pulsatility index (PI) and the resistant index (RI) were determined at the beginning, and the associations with irregular bleeding were evaluated three and six months after insertion. Results: In group A: LNG-IUS, some women registered irregular bleeding (28 percent) than in the Cu-IUD group (52 percent) at the beginning of the study (P&lt;0.001). There was bleeding irregularity (73 percent) in the group (A): LNG-IUS and severe menstrual bleeding (68 percent) in the Cu-IUD group. The uterine artery PI was associated with bleeding irregularity at value of 1.40, with a curve area (AUC) of 0.91, 90 percent sensitivity, and 100 percent specificity. Uterine artery RI was associated with 0.65 with 0.22 AUC bleeding irregularity, 95 percent sensitivity and accuracy 100 percent. Conclusion: LNG - IUS related irregular bleeding was linked to changes in the blood flow of uterine arteries that were not evident among Cu - IUD users.

Analysis of the effect and safety of levonorgestrel-releasing intrauterine system on patients with breast cancer who take tamoxifen

Objective To analyze the effect and safety of levonorgestrel-releasing intrauterine system(LNG-IUS) for the premenopausal patients with breast cancer who took tamoxifen as adjuvant therapy. Methods From June 2014 to June 2016, 84 patients with breast cancer who met the inclusion criteria in the First People′s Hospital of Xiaoshan District were randomly divided into two groups according to the digital table.The treatment group (39 cases) underwent LNG-IUS insertion, while the control group (45 cases) received no LNG-IUS insertion.The general condition of patients before the use of tamoxifen and LNG-IUS was evaluated.Transvaginal ultrasound was used to measure the thickness of endometrium, hysteroscope was used for pathological examination of endometrium and the measurement of ER/PR expression, and blood lipid level was also detected.All above was done before the treatment of tamoxifen and LNG-IUS, 1 year after treatment and 2 years after treatment. Results Before the therapy, there were no statistically significant differences between the two groups in general condition and uterine cavity condition(all P>0.05). After 1 year, the incidences of endometrial polyp, endometrial hyperplasia/secretion, benign lesion and endometrial atrophy in the treatment group were 2.6%, 5.1%, 15.4%, 76.9%, respectively, which in the control group were 6.7%, 20.0%, 17.8%, 55.6%, respectively.the differences between the two groups were statistically significant(χ2=4.06, 4.22, all P<0.05). After 2 years, the incidences of endometrial polyp, endometrial hyperplasia/secretion, benign lesion and endometrial atrophy in the treatment group were 0.0%, 2.6%, 84.6%, respectively, which in the control group were 11.1%, 15.6%, 60.0%, respectively, the differences between the two groups were statistically significant(χ2=4.608, 4.092, 6.203, all P<0.05). Conclusion LNG-IUS can prevent the benign endometrial lesions of breast cancer patients caused by tamoxifen therapy after surgery, and can decrease the incidence of endometrial polyp and endometrial hyperplasia/secretion, while increase the incidence of endometrial atrophy, without increasing the recurrence risk of breast cancer. Key words: Intrauterine devices, Medicated; Levonorgestrel; Tamoxifen; Breast neoplasms; Premenopause; Endometrium

Endometriosis-associated pain scores and biomarkers in users of the etonogestrel-releasing subdermal implant or the 52-mg levonorgestrel-releasing intrauterine system for up to 24 months

Objectives: The aims of the study were to correlate endometriosis-associated pain, evaluated by visual analogue scale (VAS) scores, with serum levels of etonogestrel (ENG), levonorgestrel (LNG), CA-125 and soluble CD23 in users of the ENG implant or the 52-mg LNG-releasing intrauterine system (52 mg LNG-IUS) for up to 2 years after device placement.Methods: A randomised trial was conducted at the University of Campinas Medical School, Brazil. All participants (n = 103) had had endometriosis-associated chronic pelvic pain or dysmenorrhoea, or both, for more than 6 months. Participants were randomly assigned to use an ENG implant (experimental treatment) or a 52-mg LNG-IUS (active comparator). Follow-up was conducted 6 monthly for up to 24 months after device placement. Dysmenorrhoea and chronic pelvic pain were evaluated using a VAS and the scores were correlated with serum levels of ENG, LNG, CA-125 and soluble CD23.Results: Both progestin-only contraceptives significantly reduced VAS scores for dysmenorrhoea and chronic pelvic pain and reduced serum levels of soluble CD23 (p < 0.001). Serum levels of CA-125 decreased only in the ENG implant group after 24 months’ use of the device (p < 0.001). No correlation was found between pain scores and ENG or LNG serum levels over time (p > 0.005).Conclusion: Both contraceptives improved dysmenorrhoea and chronic pelvic pain scores in women with endometriosis-associated pain and they reduced serum levels of soluble CD23; however, serum levels of CA-125 were reduced only in ENG implant users over the 24-month study period.

Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis.

Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50years, ≥50years, and mixed). We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR)=1.16 (95% CI 1.06-1.28, I2 =78%, P<.01); for women aged <50years, OR=1.12 (95% CI 1.02-1.22, I2 =66%, P=.02); and for women aged ≥50years, OR=1.52 (95% CI 1.34-1.72, I2 =0%, P=.84). Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.

Baseline Serum HE4 But Not Tissue HE4 Expression Predicts Response to the Levonorgestrel-Releasing Intrauterine System in Atypical Hyperplasia and Early Stage Endometrial Cancer.

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a conservative management option for atypical hyperplasia (AH) and low grade early stage endometrial cancer (EEC), but around 1 in 3 patients fail to respond to treatment. The aim of this study was to investigate if serum and/or tissue HE4 expression could predict response to LNG-IUS therapy. Patients with AH or presumed Stage I EEC had serum and endometrial samples taken at baseline and at 3-month intervals over 12 months post-insertion of LNG-IUS. 74 patients were recruited and baseline demographics recorded. Of 57 patients for whom response was histologically determinable, 39 (68%) were responders and 18 (32%) non-responders. Mean baseline serum HE4 was significantly lower in responders (62.1 ± 1.1 pM, 95% confidence interval (CI) 52.7–73.2), compared to non-responders (125.6 ± 1.3 pM, 95% CI 74.5–211.7, p = 0.014), including when considering age, BMI, menopausal status, smoking status, and histological grade as covariables (p = 0.005). Baseline tissue HE4 expression was not significantly different in responders compared to non-responders (p = 0.999). Responders showed a significant mean reduction (−9.8 ± 3.4%, 95% CI −16.7 to −2.8%, p = 0.008) in serum HE4 between baseline and 3 months (p = 0.008), whereas non-responders showed no significant change (p = 0.676). Neither responders nor non-responders showed a significant percentage change in serum HE4 from baseline beyond 3 months (p > 0.05). Change in serum HE4 between baseline and 3 and 6 months and tissue HE4 tissue expression between baseline and 3, 6, and 12 months was not significantly different in responders compared to non-responders (p > 0.05). This study suggests that baseline serum HE4, but not baseline tissue HE4 expression, is independently predictive of response to the LNG-IUS and could be used to guide management decisions.