Levonorgestrel-releasing Intrauterine System Group Research Articles

A 52-mg levonorgestrel-releasing intrauterine system vs bipolar radiofrequency nonresectoscopic endometrial ablation in women with heavy menstrual bleeding: long-term follow-up of a multicenter randomized controlled trial

BACKGROUNDThe symptom of heavy menstrual bleeding has a significant impact on professional, physical and social functioning. In 2021, results from a randomized controlled trial comparing a 52 mg levonorgestrel-releasing intrauterine system and radiofrequency non-resectoscopic endometrial ablation as treatments for women with heavy menstrual bleeding were published. Both treatment strategies were equally effective in treating heavy menstrual bleeding during a two-year follow-up. However, long-term results are also relevant for both patients and health care providers. OBJECTIVEThe aim of this study was to assess long-term differences in reintervention risk and menstrual blood loss in women with the symptom of heavy menstrual bleeding treated according to a strategy starting with a 52 mg levonorgestrel-releasing intrauterine system or radiofrequency non-resectoscopic endometrial ablation. STUDY DESIGNThis study was a long-term follow-up study of a multi-center randomized controlled trial (MIRA trial) in which women were allocated to either a 52 mg levonorgestrel-releasing intrauterine device (n=132) or radiofrequency non-resectoscopic endometrial ablation (n=138). Women from the original trial were contacted to fill out six questionnaires. The primary outcome was reintervention rate after allocated treatment. Secondary outcomes included surgical reintervention rate, menstrual bleeding measured by the Pictorial Blood Loss Assessment Chart, (disease-specific) quality of life, sexual function and patient satisfaction. RESULTSFrom the 270 women that were randomized in the original trial, 196 women (52 mg levonorgestrel-releasing intrauterine system group: n=94; radiofrequency non-resectoscopic endometrial ablation group: n=102) participated in this long-term follow-up study. Mean follow-up duration was 7.4 years (range 6-9 years). The cumulative reintervention rate (including both medical and surgical reinterventions) was 40.0% (34/85) in the 52 mg levonorgestrel-releasing intrauterine system group and 28.7% (27/94) in the radiofrequency non-resectoscopic endometrial ablation group (relative risk: 1.39; 95% confidence interval: 0.92-2.10). The cumulative rate of surgical reinterventions only was significantly higher for patients with a treatment strategy starting with a 52 mg levonorgestrel-releasing intrauterine system compared to radiofrequency non-resectoscopic endometrial ablation (35.3% [30/85] vs. 19.1% [18/94]; relative risk: 1.84; 95% confidence interval: 1.11-3.10). However, hysterectomy rate was similar: 11.8% [10/94] in the 52 mg levonorgestrel-releasing intrauterine system group and 18.1% [17/102] in the radiofrequency non-resectoscopic endometrial ablation group (relative risk: 0.65; 95% confidence interval: 0.32-1.34). Most reinterventions took place during the first 24 months of follow-up. A total of 171 Pictorial Blood Loss Assessment Chart scores showed a median bleeding score of 0.0. No clinically relevant differences were found regarding quality of life, sexual function and patient satisfaction. CONCLUSIONThe overall risk of reintervention after long-term follow-up was not different for women treated according to a treatment strategy starting with a 52 mg levonorgestrel-releasing intrauterine system as compared to a strategy starting with radiofrequency non-resectoscopic endometrial ablation. Yet, women allocated to a treatment strategy starting with a 52 mg levonorgestrel-releasing intrauterine system had a significantly higher risk for surgical reintervention, which was driven by an increase in subsequent endometrial ablation. Both treatment strategies remain effective in lowering menstrual blood loss over the long-term. The results of this long-term follow-up study help physicians to optimize counseling of women suffering from the symptom of heavy menstrual bleeding. Optimized counseling will enable women to make a well-informed choice regarding treatment.

The role of levonorgestrel-releasing intrauterine system for recurrence prevention after conservative surgery among patients with coexistent ovarian endometrioma and diffuse adenomyosis: A retrospective case control study with long-term follow up.

When ovarian endometrioma coexist with adenomyosis, the risk of postoperative recurrence increased. How is the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on symptomatic recurrence for those patients was unknown. This study retrospectively analyzed 119 women with coexistent endometrioma and diffuse adenomyosis who received laparoscopic excision of pelvic endometriosis from January 2009 to April 2013. Women were categorized into two groups: intervention group with LNG-IUS and control group with expectant observation after surgery. Data were compared in terms of preoperative history, laboratory and intraoperative findings, and clinical outcomes during follow-up, including pain regression, changes in uterine volume and recurrence. During a median 79 months (range, 6-107) of follow-up, patients with LNG-IUS experienced a significantly lower symptomatic recurrence of either ovarian endometrioma or dysmenorrhea (11.1% vs. 31.1%, p=0.013), compared with women under expectant observation by Kaplan-Meier survival analysis (χ2=5.448, p=0.020) and Cox univariate assessment (hazard ratio of 0.336, 95% confidence interval 0.128-0.885, p=0.027). Patients treated with LNG-IUS demonstrated a more prominent reduction in uterine volume (-14.1±20.9vs. 8.7±48.8, p=0.003) and higher percentage of complete pain remission (95.6% vs. 86.5%). For multivariate analysis, use of LNG-IUS (aHR 0.159, 95%CI 0.033-0.760, p=0.021) and severity of dysmenorrhea (aHR 4.238, 95%CI 1.191-15.082, p=0.026) were two independent factors associated with overall recurrence. Postoperative insertion of LNG-IUS may prevent recurrence in symptomatic women with comorbidity of ovarian endometrioma and diffuse adenomyosis.

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

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

The effect of a single session of videogame-training on balance performance in children with cerebral palsy

Endometrial hyperplasia is associated with varying risk of endometrial cancer. The aim of this review is to assess effectiveness of levonorgestrel-releasing intrauterine system (LNG-IUS), compared to systemic progestins, in management of endometrial hyperplasiaA search on studies comparing LNG-IUS to systemic progestins was conducted on Scopus, Web of science, Cochrane, PubMed and Embase databases, from the date of inception to September 20th, 2020. Studies were excluded if they were non-comparative, animal studies, review articles, case reports, case series, and conference papers. Primary outcomes include resolution/regression rate, failure rate, and hysterectomy rate. Analysis was pooled using random effect model and was expressed as pooled odds ratios (OR) and 95% confidence interval (CI). Quality assessment was performed using Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) assessment tool. MOGGE Meta-analysis Matrix was used to illustrate multiple subgroup analyses.Out of 341 studies retrieved from literature search, 12 were eligible. LNG-IUS yielded significantly higher resolution/regression rate (91.3% vs 68.6%, OR 3.42, 95% CI 1.86-6.30). Failure and hysterectomy rates were significantly lower in LNG-IUS group compared to systemic progestins’ group (19.2% vs. 32.3%, OR 0.34, 95% CI 0.20-0.57 and 9.3% vs. 24.1%, OR 0.41, 95% CI 0.29-0.57, respectively). Subgroup analysis of studies including complex hyperplasia only did not show significant difference in resolution/regression rate was not statistically significant.LNG-IUS is associated with high success rate in management of women with endometrial hyperplasia. However, specific effectiveness of LNG-IUS on more advanced histologic subtypes is less studied.

Levonorgestrel-releasing intrauterine system versus oral medroxyprogesterone acetate in infertile women with endometrial hyperplasia without atypia

Research questionHow 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)? DesignThis 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. ResultsBaseline 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%). ConclusionEndometrial 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.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding

Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding. This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding. This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function. We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups. Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared withwomen who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments.

Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

Comparison of diagnostic accuracy between endometrial curettage and aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group study.

ObjectiveTo compare the diagnostic accuracy of dilatation and curettage (D&C) versus endometrial aspiration biopsy in follow-up evaluation of patients treated with progestin for endometrial hyperplasia (EH)MethodsA prospective multicenter study was conducted from 2015 to 2018. Patients with EH were treated with progestin, one of the following three treatment regimens: oral medroxyprogesterone acetate (MPA) 10 mg/day for 14 days per cycle, continuous MPA 10 mg/day or the levonorgestrel-releasing intrauterine system (LNG-IUS). At 3 or 6 months of treatment, endometrial tissues were obtained via 2 methods in each patient: aspiration biopsy, followed by D&C. The primary outcome was the consistency of the histologic results between the 2 methods. The secondary outcome was the regression rate at 6 months of treatment.ResultsThe study population comprised 65 patients (55 with non-atypical hyperplasia, 10 with atypical hyperplasia). During the follow-up, a comparison of the pathologic results from aspiration biopsy and D&C was carried out for the 65 cases. Thirty-eight cases were diagnosed as EH by D&C. Among these, only 24 were diagnosed with EH from aspiration biopsy, for a diagnostic concordance of 63.2% (ĸ=0.59). Forty-four patients were followed up at 6 months, and the regression rate was 31.8% (14/44). Responses were obtained for 41.7% (5/12) of the cyclic MPA group, 58.3% (7/12) of the continuous MPA group and 10% (2/20) of the LNG-IUS group.ConclusionAs a follow-up evaluation of patients treated with progestin for EH, aspiration biopsy is less accurate than D&C and might not be a reliable method.Trial RegistrationClinicalTrials.gov Identifier: NCT02412072

The influence of the levonorgestrel‐releasing intrauterine system position on bleeding patterns in reproductive age women

To determine whether users of the non-fundal levonorgestrel-releasing intrauterine system (LNG-IUS) present with unfavorable bleeding patterns more frequently than fundal LNG-IUS users. A prospective cohort was conducted from June, 2016 to January, 2018 involving women aged 18-45years who wished to use the LNG-IUS as contraception and had no contraindications, endometrial polyps, submucosal myomas, irregular menstrual cycle, or anticoagulant use. Two study groups comprised women using fundal insertion and non-fundal insertion LNG-IUS. Bleeding was evaluated using a diary and pictogram chart. Of the 92 women who participated in the study, those with non-fundal LNG-IUS insertion sustained bleeding at rates greater than 83% (31) in the first 3months of use, and 58% (14) at 6months, versus 51% (22) at 3months and 33% (19) at 6months in those with fundal insertion (P=0.002 at 3months; P=0.037 at 6months). Blood loss in the non-fundal LNG-IUS group was higher than in the fundal LNG-IUS group according to pictograms drawn by participants. Women with non-fundal LNG-IUS placement had a higher frequency of sustained bleeding and blood loss volume according to self-reported charts than those with fundal LNG-IUS placement.

Effect of pretreatment with a levonorgestrel-releasing intrauterine system on IVF and vitrified-warmed embryo transfer outcomes in women with adenomyosis.

Does the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) improve the ongoing pregnancy rate of vitrified-warmed embryo transfer in women with adenomyosis undergoing IVF? This retrospective study included 358 women with adenomyosis undergoing IVF. Of these, 134 women were enrolled in the LNG-IUS group and another 224 women were in the control group. All women were screened for adenomyosis by transvaginal ultrasound and magnetic resonance imaging (MRI). There was no significant difference in the ages of women, FSH, cause of infertility, body mass index, total dose of gonadotrophin used and number of oocytes collected between the two groups. All comparisons performed were between patients undergoing vitrified-warmed embryo transfer. Statistical differences were found in the ongoing pregnancy rates (41.8% vs 29.5%, P = 0.017) between the LNG-IUS group and control group. Logistic regression analysis showed that the odds ratio (OR) of ongoing pregnancy was significantly increased with LNG-IUS usage (adjusted OR = 1.628, 95% confidence interval 1.011-2.622). Also, differences were found in implantation rates (32.1% vs 22.1%, P = 0.005) and clinical pregnancy rates (44% versus 33.5%, P=0.045) between the LNG-IUS group and control group. The results of this study offer some support for evaluating the effect of pretreatment with LNG-IUS in women with adenomyosis in future randomized controlled trials.

Effects of a levonorgestrel intrauterine system versus acopper intrauterine device on menstrual changes and uterine arteryDoppler.

To compare the effects of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a copper intrauterine device (Cu-IUD) on menstrual changes and uterine artery Doppler indices. A randomized clinical trial was conducted at Menoufia University Hospital, Egypt, between December 2016 and August 2017. 306 multiparous women desiring intrauterine contraception were randomly assigned to LNG-IUS (n=152) or Cu-IUD (n=154). Uterine artery pulsatility index (PI) and resistant index (RI) were measured before use, and 3 and 6months after insertion, and associations with abnormal bleeding were evaluated. Irregular bleeding was initially reported by 31 (74%) of 42 women in the LNG-IUS group, and heavy menstrual bleeding by 53 (67%) of 79 women in the Cu-IUD group. Incidence of abnormal bleeding decreased over the 6-month study period. Uterine artery PI was significantly correlated with abnormal bleeding at a cutoff of 1.35 with area under the curve (AUC) 0.93, sensitivity 88%, and specificity 100%, whereas uterine artery RI was significantly correlated with abnormal bleeding at a cutoff of 0.62 with AUC 0.1, sensitivity 96%, and specificity 100%. LNG-IUS-related abnormal bleeding was associated with changes in uterine artery blood flow that were not evident among Cu-IUD users. Pan African Clinical Trials Registry: PACTR201701001900640.

High intensity focused ultrasound treatment of adenomyosis: a comparative study

Objective: To compare the treatment efficacy and safety of high intensity focused ultrasound (HIFU) on its own, HIFU combined with levonorgestrel-releasing intrauterine system (LNG-IUS) and HIFU combined with gonadotropin-releasing hormone agonist (GnRHa).Method: Seventy-eight patients with adenomyosis who underwent HIFU treatment were retrospectively analyzed. Among them, 45 patients were treated only with HIFU, 15 patients were treated with HIFU combined with LNG-IUS and 18 patients were treated with HIFU combined with GnRHa. Dysmenorrhea scores, menstrual blood volumes, uterine volumes and adenomyotic lesion volumes were evaluated 1, 6 and 12 months after HIFU.Result: After treatment, dysmenorrhea score, menstrual blood volume, uterine volume and adenomyotic lesion volume significantly decreased in all three groups (p < 0.05). No significant difference was observed among the HIFU group, HIFU with LNG-IUS group and HIFU with GnRHa group 1 month after HIFU. However, 6 and 12 months after HIFU, dysmenorrhea score, menstrual blood volume, uterine volume and adenomyotic lesion volume decreased significantly more in the HIFU with LNG-IUS group and HIFU with GnRH-a group than in the group treated with HIFU on its own (p < 0.05).Conclusion: HIFU can be effectively used in the management of adenomyosis. Based on the results of this study with a limited number of patients, our study suggested that combining HIFU with LNG-IUS or GnRHa may provide a superior clinical effect compared to HIFU treatment on its own.

Efficacy of levonorgestrel releasing intrauterine system as a postoperative maintenance therapy of endometriosis: A meta-analysis

ObjectiveTo compare the efficacy of levonorgestrel releasing intrauterine system (LNG-IUS) with other treatments as a postoperative maintenance therapy for endometriosis in terms of pain reduction, recurrence prevention, side effects and patients’ satisfaction. Study designWe searched MEDLINE, EMBASE, and the Cochrane Library from January 1986 until February 2018. Two evaluators independently extracted and reviewed prospective and retrospective articles based on pre-determined selection criteria. Outcomes were expressed as mean difference (MD), risk ratios (RR) or odds ratios (OR) in a meta-analysis model, using Revman software. ResultsAmong the 962 studies, 7 studies were selected: 7 studies included 4 randomized controlled trials with 212 patients, 1 prospective cohort study with 88 patients, and 2 retrospective studies with 191 patients. A meta-analysis showed that LNG-IUS was significantly effective in reducing pain after surgery (MD = 12.97, 95% confidence interval (CI): 5.55–20.39), with a comparable effect to gonadotropin-releasing hormone analogues (MD = −0.16, 95% CI: −2.02 to 1.70). LNG-IUS was also effective in decreasing the recurrence rate (RR = 0.40, 95% CI: 0.26–0.64), with an effect comparable to OC (OR = 1.00, 95% CI: 0.25–4.02) and danazol (RR = 0.30, 95% CI: 0.03–2.81). Furthermore, patients’ satisfaction with LNG-IUS was significantly higher than that with OC (OR = 8.60, 95% CI: 1.03–71.86). However, vaginal bleeding was significantly higher in the LNG-IUS group than in the gonadotropin-releasing hormone analogue group (RR = 27.0, 95% CI: 1.71–425.36). ConclusionOur meta-analysis found a positive effect of LNG-IUS as a postoperative maintenance therapy for endometriosis on pain relief, prevention of dysmenorrhea recurrence, and patients’ satisfaction.

Cardiovascular risk markers among obese women using the levonorgestrel-releasing intrauterine system: A randomised controlled trial

According to international guidelines, women with obesity without other comorbidities can safely use any hormonal contraceptive (HC). However, limited information is available about contraceptive safety for women with obesity since obesity is an exclusion criterion of most contraceptive clinical trials. As such little is known about the possible risks of HC exposure for women with obesity without comorbidities. One way to assess possible long-term risks in this population, even prior to the development of any clinical disease, is to measure alterations in subclinical atherosclerosis markers. We evaluated the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on subclinical markers of cardiovascular risk in women with obesity. This is a randomised clinical trial in which 106 women with obesity [body mass index (BMI)≥30kg/m2] were randomised to the LNG-IUS (n=53) or to non-hormonal methods (n=53) and followed for 12 months. We evaluated waist circumference (WC), blood pressure, blood glucose, insulin, lipid profile, and endothelial function markers (carotid intima-media thickness, brachial artery flow-mediated dilation, and carotid arterial stiffness). At 12 months, BMI (p=0.005), WC (p=0.045), and glucose levels (p=0.015) were significantly lower in the LNG-IUS group than in the control group. We did not find any clinically relevant changes in subclinical markers of cardiovascular risk among with obesity women at 12 months after LNG-IUS placement compared to users of non-hormonal contraceptive methods.

Comparison of Levonorgestrel-Releasing Intrauterine System, Medroxyprogesterone and Norethisterone for Treatment of Endometrial Hyperplasia without Atypia: A Randomized Clinical Trial

Objective:to assess the efficacy, acceptability and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) compared to oral Medroxyprogesterone (MPA) and Norethisterone (NETA) for treatment of endometrial hyperplasia (EH) without atypia in perimenopausal women. Methods:This randomized clinical study included 150 perimenopausal women with endometrial hyperplasia (EH) without atypia who were randomly assigned into three groups; 50 patients received 15 mg Medroxyprogesterone acetate (MPA), 50 patients received 15 mg Norethisterone acetate (NETA) and 50 patients in whom levonorgestrel-releasing intrauterine system (LNG-IUS) was inserted. Endometrial sampling was repeated after 6 months of therapy. Primary outcome was regression of EH while secondary outcomes included side effects, patient acceptability and cost of treatment over six months. Results:There was no significant difference between the three groups regarding regression of EH (p<0.05). The LNG-IUS has the highest cost and acceptability (p<0.001). There was a significant higher women suffering from nausea in NETA group (p<0.05), acne in MPA group(P<0.05) and vaginal discharge in LNG-IUS group(p<0.05). Conclusion:In low-income and developing countries where the LNG-IUS is non affordable or unavailable, the use of norethisterone seems a viable cost-effective therapy in patients with endometrial hyperplasia without atypia.

Acceptability of intrauterine contraception among women living with human immunodeficiency virus: a randomised clinical trial

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).

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. The overall quality of evidence was rated using GRADE methods. Four randomised controlled trials involving 543 women were identified and are included in this review. In the included studies, the active treatment arm was the 20 μg/day levonorgestrel-releasing intrauterine system (LNG-IUS) plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS led to a reduction in the incidence of endometrial polyps over both a 12-month period (Peto OR 0.22, 95% CI 0.08 to 0.64, 2 studies, n = 212, I² = 0%) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39, 4 studies, n = 417, I² = 0%, moderate quality evidence). Also the LNG-IUS led to a reduction in the incidence of endometrial hyperplasia over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67, four studies, n = 417, I² = 0%, moderate quality evidence). However, it should be noted that the number of events of endometrial hyperplasia was low (n = 6). None of the trials were sufficiently powered to detect whether LNG-IUS leads to significant changes in the incidence of endometrial cancer in tamoxifen users. At 12 months of follow-up abnormal vaginal bleeding or spotting was more common in the LNG-IUS treatment group (Peto OR 7.26, 95% CI 3.37 to 15.66, 3 studies, n = 376, I² = 0%, moderate quality evidence). By 24 months of follow-up, abnormal vaginal bleeding or spotting occurred less frequently compared to 12 months of follow-up in the LNG-IUS treatment group but was still more common than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10, 2 studies, n = 233, I² = 0%, moderate quality evidence). By 60 months of follow-up, no cases of abnormal vaginal bleeding or spotting were reported in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). There was no evidence of a difference between the LNG-IUS treatment group and controls for these outcomes. The quality of the evidence was judged as moderate, due to limited sample sizes and low event rates for the outcome comparisons. The LNG-IUS reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS increased abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. There is no clear evidence from the available randomised controlled trials that the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available randomised controlled trials that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.

Levonorgestrel-releasing intrauterine system versus low-dose combined oral contraceptive for treatment of adenomyosis uteri: a randomized clinical trial

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. © 2015 Elsevier Inc. All rights reserved.

Body composition and resting metabolic rate of perimenopausal women using continuous progestogen contraception

Objective The effect on body composition and in particular on fat mass (FM) of 12 months’ use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in the perimenopause.Methods An observational study comprised 102 perimenopausal women: 42 received a 75 μg DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and again after 12 months.Results FM did not change in the control group (− 0.5 ± 1.6%) but significantly increased in the LNG-IUS group (+ 1.1 ± 2.9%; p = 0.02 vs. controls) and in the DSG group (+ 2.8 ± 3.5%; p = 0.0001 vs. controls; p = 0.02 vs. LNG-IUS). Women treated with DSG or the LNG-IUS showed a non-significant increase in body weight, body mass index and waist circumference. RMR did not significantly vary in the control group (− 3.8 ± 292.9 kJ/ 24 h) and tended to decrease but not significantly in the LNG-IUS (115.5 ± 531.8 kJ/ 24 h) and DSG groups (305.9 ± 556.9 kJ/24 h).Conclusions The results of this preliminary study seem to indicate that in perimenopausal women continuous use of the DSG-only pill and to a lesser extent the LNG-IUS may favour FM accumulation.