Cost-effectiveness analysis of levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg versus other long-acting reversible contraceptives for contraception in Spain.

INTRODUCTION: Condoms and combined oral contraceptive pills are widely used in Spain with high failure rates. Long-Acting Reversible Contraceptive (LARC) methods offer better efficacy and adherence and reduce unintended pregnancies (UP) compared with short-acting reversible contraceptive (SARC) methods. OBJECTIVE: To assess the cost-effectiveness of LNG-IUS 52 mg (Mirena®) versus other LARC for contraception in Spain. MATERIALS AND METHODS: A Markov model with annual cycles and an eight-year time horizon was developed from the Spanish national healthcare system (NHS) perspective, considering costs for contraceptive method acquisition, health care resources (HCR) and UP. Effectiveness was based on failure and discontinuation rates. Sensitivity analyses were performed to test the model's robustness. RESULTS: LNG-IUS 52 mg (Mirena®) resulted in lower costs and fewer UP versus LNG-IUS 13.5 mg (Jaydess®), Implant (Implanon®) and Copper IUD. LNG-IUS 52 mg (Levosert®) prevented the same UP events at a higher cost. LNG-IUS 19.5 mg (Kyleena®) was the most effective option, due to a lower discontinuation rate. CONCLUSIONS: LNG-IUS 52 mg (Mirena®) is the least costly LARC, driven by lower acquisition costs and reduced HCR utilisation. Increasing LNG-IUS 52 mg (Mirena®) uptake in contraception could generate further cost savings for the Spanish NHS and reduce economic burden of UP.

Levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena^®) is an effective and cost-saving long-acting reversible contraceptive (LARC) method compared with other similar methods in Spain over an eight-year time horizon, and Kyleena^® was the most effective option.

Usage of the levonorgestrel releasing intrauterine system in perimenopause.

Levonorgestrel releasing intrauterine system have excellent contraceptive efficacy with simultaneous lowering of menstruation's blood loss. It could be used for therapy of endometrial hyperplasia in perimenopause. In position of gestagen part of the hormone replacement therapy it has high control of endometrial proliferation. It is conjoined with the zero increasing of risk of thromboembolic disease in combination with transdermal oestrogen's application.

Efficacy of hysteroscopic levonorgestrel­releasing intrauterine device fixation in the treatment of adenomyosis: A cohort study.

The present study aimed to investigate the efficacy of hysteroscopic levonorgestrel-releasing intrauterine device (LNG-IUD) fixation surgery in the treatment of adenomyosis through a cohort study. The cohort study was performed at the Affiliated Jinhua Hospital of Wenzhou Medical University (Jinhua, China). A total of 31 women with adenomyosis were initially recruited from June 2020 to June 2022 and divided into an experimental group and a control group. The experimental group underwent hysteroscopic LNG-IUD fixation surgery and the control group underwent conventional implantation of the levonorgestrel-releasing intrauterine system. The assessed efficacy outcomes included the time of LNG-IUD expulsion, postoperative vaginal bleeding time, dysmenorrhea, and the menstrual blood loss score (MBLS). A total of 31 participants completed the research. The LNG-IUD expulsion rate was 6.25 and 60% (P<0.05) in the experimental and control group, respectively. The LNG-IUD in place time was 20.50 months (Q1, 15.75; Q3, 24.00) in the experimental group and 10.00 months (Q1, 6.50; Q3, 15.00) in the control group (P<0.05); the time of vaginal bleeding after surgery in the experimental and control groups were 12.50 days (9.25, 16.25) and 120.00 days (75.00, 120.00), respectively (P<0.05). Multiple-factor Cox regression analysis revealed that the LNG-IUD expulsion in patients with adenomyosis is associated with the hysteroscopic LNG-IUD fixation surgery [hazard ratio (HR), 1954.09], uterine cavity depth (HR, 16.63), MBLS (HR, 1.14), history of gonadotropin-releasing hormone agonist treatment in the previous 6 months (HR, 2.10), history of vaginal delivery (HR, 1.79) and history of cervical laceration (HR, 3.69). In conclusion, hysteroscopic LNG-IUD fixation reduces the rate of LNG-IUD expulsion, prolongs the time of LNG-IUD in the uterine cavity, reduces the time of postoperative vaginal bleeding, relieves the symptoms of dysmenorrhea and reduces the menstrual volume in the patients with adenomyosis. The present trial was retrospectively registered in the Chinese Clinical Trial Registry on 28th December 2023 (registration no. ChiCTR2300079233).

The use of LNG-IUS-19.5 mg in daily gynecological routine practice in Germany: data from the Kyleena™ Satisfaction Study (KYSS).

PURPOSE: The Kyleena™ Satisfaction Study (KYSS) provided the first data on 19.5 mg levonorgestrel-releasing intrauterine system (LNG-IUS-19.5 mg) use in routine clinical practice. Here we report results from the German participants in KYSS. METHODS: This prospective, observational, single-arm cohort study recruited women who independently chose to use LNG-IUS-19.5 mg during routine counseling in Germany. Overall satisfaction and bleeding profile satisfaction, continuation rates, and safety profile were evaluated at 12 months or premature end of observation (EoO). RESULTS: In the German study population, LNG-IUS-19.5 mg placement was attempted in 508 women and successful in 506 women. Mean age was 32.3 years, and 60.0% (n = 305/508) were parous. Placement was considered easy and associated with no more than mild pain, even in younger and nulliparous participants. Of those with satisfaction data available, 87.6% (n = 388/443) were satisfied with LNG-IUS-19.5 mg at 12 months/EoO. Satisfaction was similar for parous (86.9%, n = 238/274) and nulliparous (88.8%, n = 150/169) women, and was independent of age, prior contraceptive method, or reason for choosing LNG-IUS-19.5 mg. Most participants (73.6%, n = 299/406) were also satisfied with their bleeding profile at 12 months/EoO, independent of parity, age, prior contraceptive method, presence of amenorrhea or dysmenorrhea severity. The 12-month continuation rate was 84.1% (n = 427/508). Most discontinuations were due to loss to follow-up (8.5%, n = 43/508) or treatment-emergent adverse events (TEAEs) (4.7%, n = 24/508). TEAEs were reported in 12.6% (n = 64) of participants, with 9.3% (n = 47) considered to have an LNG-IUS-19.5 mg-related TEAE. CONCLUSION: Our real-world findings on LNG-IUS-19.5 mg use in German KYSS participants reflected its suitability for a broad population, including young and nulliparous women. CLINICAL TRIAL REGISTRATION: NCT03182140 (date of registration: June 2017).

Laparoscopic adenomyomectomy combined with levonorgestrel-releasing intrauterine system is effective for long-term management of adenomyosis.

BACKGROUD: Laparoscopic adenomyomectomy combined with intraoperative placement of levonorgestrel-releasing intrauterine device (LNG-IUS) is a novel conservative surgical procedure for adenomyosis. Our study aimed to compare the efficacy of surgery with or without intraoperative placement of LNG-IUS treatment in adenomyosis. METHODS: We retrospectively reviewed the medical records of adenomyosis patients who received laparoscopic adenomyomectomy from January 2014 to April 2020, finally including 70 patients undergoing surgery-LNG-IUS as group A and 69 patients undegoing surgery only as group B. Risk factors for three-year relapse were analyzed using Cox's multivariate proportional hazard analysis. RESULTS: Visual analog scale and Mansfield-Voda-Jorgensen Menstrual Bleeding Scale scores of group A at 3, 6, 12, 24, and 36 months were significantly lower than those of group B at the corresponding points (P < .001 for both scales). Individuals in both groups showed statistically significant symptom relief. The recurrence rate in group A was significantly lower than that in group B at 36 months after the surgery (2.94% vs. 32.84%, P < .001). A cox proportional hazard model showed that relapse was significantly associated with coexisting ovarian endometriosis (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 1.33-7.02, P = .015). Patients who received surgery-LNG-IUS had a lower risk of recurrence than those with surgery-alone (aHR, 0.07; 95% CI, 0.016-0.31, P < .001). CONCLUSIONS: Conservative surgery with intraoperative placement of LNG-IUS is effective and well-accepted for long-term therapy with a lower recurrence rate for adenomyosis. Coexistent ovarian endometriosis is a major factor for adenomyosis relapse.

Modified Fixation of Levonorgestrel-releasing Intrauterine System for the Treatment of Adenomyosis / 中山大学学报(医学科学版)

ObjectiveTo introduce a fixation technique with the modified levonorgestrel-releasing intrauterine system （LNG-IUS） and evaluate its efficacy in the treatment of adenomyosis patients with previous LNG-IUS expulsion. MethodsA retrospective analysis was done on 22 adenomyosis patients who underwent modified LNG-IUS fixation due to LNG-IUS expulsion at three hospitals from June 2022 to June 2023. The baseline clinical characteristics， operative and postoperative details were collected and analyzed. The Visual analogu scale （VAS） scores and pictorial blood loss assessment chart （PBAC） scores were measured and compared before， 3 and 6 months after the LNG-IUS fixation. ResultsThe mean operative time was （19.51±7.41） min and intraoperative bleeding was （6.71±5.30） mL. Of the patients， 13 were operated under local anaesthesia and the other 9 under intravenous anaesthesia. There were 4 operations performed by a resident doctor， 15 by an attending doctor and 3 by a senior doctor. No intraoperative or postoperative complication was found. The mean follow-up was 11.51 months and no patient had a recurrence of LNG-IUS expulsion during the follow-up period. The mean level of hemoglobin at 1 month after operation was significantly higher than that before （P<0.001）. VAS scores and PBAC scores at 3 and 6 months postoperatively were all improved significantly than those preoperatively （P<0.001）. ConclusionsEffectively preventing the recurrence of LNG-IUS expulsion， modified LNG-IUS fixation is a safe and efficient method for adenomyosis patients with previous LNG-IUS expulsion. Modified LNG-IUS fixation deserves the clinical application due to its easy operation and wide range of use on women.

Levonorgestrel-releasing intrauterine system effects on metabolic variables in PCOS.

BACKGROUND: We aimed to determine and compare the reproductive hormone level and metabolic of patients with polycystic ovary syndrome (PCOS) when treated with a levonorgestrel-releasing intrauterine system (LNG-IUS). OBJECTIVES: Sixty-four women with PCOS (Group A) and sixty-six healthy women inserted with a LNG-IUS for conception (Group B) were recruited from the Department of Obstetrics and Gynecology in Jinhua Hospital Zhejiang University School of Medicine. METHOD: We compared the general characteristics of the cases between the two groups, including age, body mass index (BMI), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), abdominal circumference (AC) and waist circumference (WC). Each patient was evaluated by transvaginal ultrasonography (TVS) to determine the number of oocytes and ovarian volume, and the intima-media thickness (IMT) of the common carotid artery was measured on an ECG image from the left common carotid artery before and six months, 12 months and 24 months after patients were inserted with the LNG-IUS. Hormone levels (follicle stimulating hormone, luteinizing hormone, serum estradiol and total testosterone), serum insulin, sex hormone binding globulin (SHBG), total cholesterol (TC), high density lipoprotein (HDL), and triglyceride (TG), were evaluated before and six months, 12 months and 24 months after patients were inserted with an LNG-IUS. The levels of testosterone (T) in the non-HA (hyperandrogenemia) group and HA group in PCOS group were compared with the baseline. We also compared cases without insulin resistance in the PCOS group with their baseline. RESULTS: Prior to LNG-IUS insertion, the PCOS group had significantly higher total testosterone levels (p < 0.05), lower HDL levels (p < 0.05), and a greater ovarian volume (p < 0.05) than the control group. Compared to baseline values, there was a significant increase in fasting glycemia at six months after LNG-IUS insertion (p < 0.05). Mean ovarian volume was significantly smaller than the volume prior to LNG-IUS insertion (p < 0.05); LDL and TC were significantly reduced when compared to baseline evaluation in the PCOS group. The remaining variables did not differ significantly during the 24 months follow-up period. The control group did not show any significant changes when compared to the period before LNG-IUS insertion. When the groups were compared after the 24-month follow-up, WC, AC, FSH, LH, T, SHBG, HDL, FINs, FAI and ovarian volume were significantly different when compared between the two groups (p < 0.05) . CONCLUSION: The LNG-IUS is an effective and safe non-surgical device and the use of this system for 24 months did not result in significant changes in the clinical and metabolic variables in women with PCOS and healthy control females.

Ulipristal acetate versus levonorgestrel-releasing intrauterine system for heavy menstrual bleeding (UCON): a randomised controlled phase III trial.

Background: Heavy menstrual bleeding affects one in four women and negatively impacts quality of life. Ulipristal acetate is prescribed to treat symptoms associated with uterine fibroids. We compared the effectiveness of ulipristal acetate and the levonorgestrel-releasing intrauterine system at reducing the burden of heavy menstrual bleeding, irrespective of the presence of fibroids. Methods: This randomised, open-label, parallel group phase III trial enrolled women over 18 years with heavy menstrual bleeding from 10 UK hospitals. Participants were centrally randomised, in a 1:1 ratio, to either three, 12-week treatment cycles of 5 mg ulipristal acetate daily, separated by 4-week treatment-free intervals, or a levonorgestrel-releasing intrauterine system. The primary outcome, analysed by intention-to-treat, was quality of life measured by the Menorrhagia Multi-Attribute Scale at 12 months. Secondary outcomes included menstrual bleeding and liver function. The trial is registered with ISRCTN, 20426843. Findings: Between June 5th, 2015 and February 26th, 2020, 236 women were randomised, either side of a recruitment suspension due to concerns of ulipristal acetate hepatoxicity. Subsequent withdrawal of ulipristal acetate led to early cessation of recruitment but the trial continued in follow-up. The primary outcome substantially improved in both groups, and was 89, (interquartile range [IQR] 65 to 100, n = 53) and 94, (IQR 70 to 100, n = 50; adjusted odds ratio 0.55, 95% confidence interval [CI] 0.26-1.17; p = 0.12) in the ulipristal and levonorgestrel-releasing intrauterine system groups. Rates of amenorrhoea at 12 months were higher in those allocated ulipristal acetate compared to levonorgestrel-releasing intrauterine system (64% versus 25%, adjusted odds ratio 7.12, 95% CI 2.29-22.2). Other outcomes were similar between the two groups and there were no cases of endometrial malignancy or hepatotoxicity due to ulipristal acetate use. Interpretation: Our findings suggested that both treatments improved quality of life. Ulipristal was more effective at inducing amenorrhoea. Ulipristal has been demonstrated to be an effective medical therapeutic option but currently its use has restrictions and requires liver function monitoring. Funding: UK Medical Research Council and National Institute of Health Research EME Programme (12/206/52).

Individualized conservative therapeutic strategies for adenomyosis with the aim of preserving fertility.

Adenomyosis is a diffuse or localized organic disease caused by benign invasion of endometrial glands and stroma into the myometrium. It is a common disease that seriously affects reproductive health of women in childbearing age. Due to the unknown etiology and pathophysiological mechanism, and the lack of unified diagnostic criteria and effective treatment methods, total or subtotal hysterectomy has become a radical treatment for adenomyosis, which will lead to the complete loss of fertility. With the continuous exploration of the treatment to adenomyotic patients who have infertility or fertility intentions, new drugs, surgical methods and treating concepts appears. Adopt individualized conservative therapeutic strategies for patients with different conditions, preserve the uterus as much as possible and protect the patient's fertility, which will play an important role on the follow-up assisted reproductive treatment and long-term management of adenomyosis.

Efficacy of Oral Medications or Intrauterine Device-Delivered Progestin in Patients with Endometrial Hyperplasia with or without Atypia: A Network Meta-Analysis.

The aim of this systematic review was to evaluate the efficacy of oral medication or intrauterine device-delivered progestins in patients with endometrial hyperplasia (EH) with or without atypia. We systematically examined PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov to identify studies reporting the regression rate of patients with EH who received progestins or non-progestins. The regression rates after different treatments were compared using a network meta-analysis in terms of the relative ratios (RRs) and 95% confidence intervals (CIs). Begg-Mazumdar rank correlation and funnel plots were performed to evaluate the publication bias. Five non-randomized studies and 21 randomized controlled trials involving 2268 patients were included in the network meta-analysis. The levonorgestrel-releasing intrauterine system (LNG-IUS) was associated with a higher regression rate than medroxyprogesterone acetate (MPA) (RR 1.30, 95% CI 1.16-1.46) in patients with EH. Among those without atypia, the LNG-IUS was associated with a higher regression rate than any of the three types of oral medications (MPA, norethisterone, or dydrogesterone (DGT)) (RR 1.35, 95% CI 1.18-1.55). According to the network meta-analysis, combining the LNG-IUS with MPA or metformin increased regression rate, while DGT was associated with the highest regression rate among all oral medications. The LNG-IUS may be the best choice for patients with EH, and combining it with MPA or metformin may further improve its efficacy. DGT may be the preferred choice for patients who are unwilling to use the LNG-IUS or who cannot tolerate its side effects.

Comparing levonorgestrel intrauterine system with hysteroscopic niche resection in women with postmenstrual spotting related to a niche in the uterine cesarean scar: a randomized, open-label, controlled trial.

BACKGROUND: Postmenstrual spotting and chronic pelvic pain after cesarean delivery are associated with the presence of niches. Levonorgestrel intrauterine system (52 mg) and hysteroscopic niche resection have been shown to relieve niche-related symptoms at 6 months after the intervention. OBJECTIVE: This trial aimed to compare the effectiveness of 52-mg levonorgestrel intrauterine system with that of hysteroscopic niche resection in reducing niche-related postmenstrual spotting. STUDY DESIGN: This randomized, open-label, controlled trial was conducted at a medical center in Shanghai, China. Women with symptoms of postmenstrual spotting after cesarean delivery, with a niche depth of at least 2 mm and residual myometrium of at least 2.2 mm on magnetic resonance imaging, and no intention to conceive within the next year were randomly assigned to receive treatment with 52-mg levonorgestrel intrauterine system or hysteroscopic niche resection. The primary outcome was the reduction in postmenstrual spotting at 6 months after randomization, defined as the percentage of women with a reduction of at least 50% in spotting days relative to baseline. Efficacy and safety were assessed using intention-to-treat analysis. RESULTS: Between September 2019 and January 2022, 208 women were randomized into the levonorgestrel intrauterine system group (N=104) or the hysteroscopic niche resection group (N=104). At the 6-month follow-up, a 50% reduction in spotting had occurred in 78.4% (80/102) of women in the levonorgestrel intrauterine system group and in 73.1% (76/104) of women in the hysteroscopic niche resection group (relative risk, 1.07 [95% confidence interval, 0.92-1.25]; P=.370). Spotting decreased over time (Ptrend=.001), with a stronger reduction observed in the levonorgestrel intrauterine system group (P=.001). There was also a significant interaction between time and treatment (P=.007). From 9 months onward, a more significant reduction in spotting was observed in the levonorgestrel intrauterine system group than in the hysteroscopic niche resection group (9 months, 89.2% vs 72.1%; relative risk, 1.24 [95% confidence interval, 1.08-1.42]; 12 months, 90.2% vs 70.2%; relative risk, 1.29 [95% confidence interval, 1.12-1.48]). Moreover, compared with the hysteroscopic niche resection group, the levonorgestrel intrauterine system group had significantly fewer postmenstrual spotting days and total bleeding days from 6 months onward (all P<.001), and less pelvic pain from 3 months onward (all P<.010). No intervention-related complications were reported in any group. During follow-up, 11 (10.8%) women reported hormone-related side effects, and 2 women (2.0%) in the levonorgestrel intrauterine system group had spontaneous partial expulsion. Meanwhile, 3 unintended pregnancies were reported in the hysteroscopic niche resection group. CONCLUSION: In women with niche-related postmenstrual spotting, the levonorgestrel intrauterine system was not more effective than hysteroscopic niche resection in reducing the number of spotting days by at least 50% at 6 months. However, the levonorgestrel intrauterine system was superior in reducing spotting from 9 months onward, and it reduced the absolute number of spotting days from 6 months onward and pelvic pain from 3 months onward.

Perforation of levonorgestrel-releasing intrauterine system found at one month after insertion: A case report.

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is widely used in contraception, menorrhagia, dysmenorrhea and to prevent endometrial hyperplasia during estrogen supplementation. Perforation is more often seen after early postpartum placement. Perforation of the LNG-IUS occurring one month after placement is rare. CASE SUMMARY: A 42-year-old female complained of progressive dysmenorrhea and increased menstrual volume. She was diagnosed with adenomyosis and the LNG-IUS was inserted in her uterine cavity. Routine ultrasound examination one month later revealed that the intra-uterine device (IUD) was not found in the uterine cavity, and further X-ray and pelvic magnetic resonance imaging showed an abnormal signal area in the left posterior region of the uterus. Laparoscopic exploratory surgery was performed and the LNG-IUS was found in the left uterosacral ligament. CONCLUSION: Perforation of a LNG-IUS occurring one month after placement is rare, and is more common in inexperienced operators and after early postpartum placement. When the operation is difficult, ultrasound monitoring is recommended to reduce the risk of IUD perforation. For patients with inadequate surgery, postoperative imaging is recommended to detect potential risks as soon as possible.

Levonorgestrel-Releasing Intrauterine System: A Promising Choice after Uterovaginal Anastomosis in Patients with Cervical Dysgenesis.

BACKGROUND: Cervical dysgenesis is categorized into cervical fragmentation, cervical fibrous cord, and cervical obstruction. The definitive management for cervical dysgenesis is either uterovaginal anastomosis (UVA) or hysterectomy. OBJECTIVE: To compare the prevalence of dysmenorrhea, hematometra, and need for dilatation after UVA with and without postprocedural placement of a levonorgestrel intrauterine system (LNG-IUS). METHODS: This was a retrospective cohort study in which 14 patients with cervical dysgenesis were included. Patients had undergone UVA between May 2015 and January 2022 at the Department of Obstetrics and Gynecology of the Cairo University Teaching Hospital. Six patients who had an LNG-IUS inserted after UVA were included in group A, and 8 patients who had undergone UVA without LNG-IUS insertion were included in group B. Transabdominal and/or transvaginal ultrasound was performed monthly for the first 3 months after LNG-IUS insertion in group A and after UVA in group B. Thereafter, the patients were followed up every 6 months. The primary outcomes were dysmenorrhea, hematometra, and need for dilatation of the anastomosis site. RESULTS: The number of patients who developed hematometra was significantly lower in group A than in group B (0 [0%] vs 6 [75%], P = .01). The number of patients who required dilatation was significantly lower in group A than in group B (0 [0%] vs 6 [75%], P = .01). There was no significant difference in the incidence of dysmenorrhea between the 2 groups. CONCLUSION: We recommend offering LNG-IUS after UVA for adolescents who present with cervical dysgenesis. LNG-IUS decreases the recurrence of hematometra and subsequent surgical interventions.

Influence of the levonorgestrel-releasing intrauterine system on the risk of breast cancer: a systematic review.

PURPOSE: The intention of this systematic review was to analyze the literature on breast cancer (BC) and the use of the levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: The literature was searched in Medline, Embase, Cochrane Library, CINAHL, Web of Science and ClinicalTrials.com and included search terms related to breast cancer and LNG-IUS. After elimination of duplicates, 326 studies could be identified and were assessed according to inclusion and exclusion criteria. In the end, 10 studies met the defined criteria and were included in the systematic review. RESULTS: 6 out of the 10 selected studies were cohort studies, three were case-control studies and one a systematic review/meta-analysis. 6 found a positive association between BC and the use of LNG-IUS. One study only found an increased risk for invasive BC in the subgroup of women aged 40-45 years. In contrast, three studies showed no indication of a higher BC risk. CONCLUSION: The results imply an increased BC risk in LNG-IUS users, especially in postmenopausal women and with longer duration of use. Positive effects of the LNG-IUS such as reduced risks for other hormonal cancers have been observed, were, however, not focus of this systematic review. The heterogeneity of the analyzed studies and vast number of confounding factors call for further investigations in this issue. Patients should be advised according to their individual risk profile and hormone-free alternatives may be considered for women with a history of BC.

Use of 52-mg Levonorgestrel-Releasing Intrauterine System in Adolescents and Young Adult Women: 3-Year Follow-Up.

STUDY OBJECTIVE: To evaluate continuance rates, bleeding patterns, and patient satisfaction with 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) use in adolescents and young adult women during the first 3 years of use DESIGN: We conducted an observational prospective study. SETTING: Family Planning Service of a tertiary hospital in Brazil PARTICIPANTS: One hundred adolescents and young women aged 16-24 years. INTERVENTION: Insertion of 52-mg LNG-IUS for the main purpose of contraception. Follow-up visits were conducted at 12, 24, and 36 months after insertion. MAIN OUTCOME MEASURES: Continuance rates, reasons for discontinuation of the method, and women's satisfaction and bleeding patterns RESULTS: Among those who were not lost to follow-up, LNG-IUS continuance rates were 89.1% (82/92), 82.9% (72/87), and 75.3% (64/85) in the first, second, and third years of use, respectively. The main reason for discontinuation was acne, followed by expulsion of/malpositioned LNG-IUS. Other reasons for discontinuation were irregular uterine bleeding, dysmenorrhea, and abdominal pain. The amenorrhea rates were 50%, 54.1%, and 39% at 12, 24, and 36 months, respectively. Spotting rates increased during the first 3 years of use (20.8%, 16.7%, and 26.6%, respectively). Adolescents and young women using the LNG-IUS showed high rates of satisfaction, with 93.9%, 100%, and 96.8% of women being very satisfied/satisfied in the first 3 years of use. Only 2 participants who continued using the LNG-IUS reported being very dissatisfied/dissatisfied in the third year of follow-up. CONCLUSION: The LNG-IUS showed high rates of continuation and satisfaction in the first 3 years of use in Brazilian adolescents and young adults. Most women reported a favorable bleeding pattern.

Levonorgestrel-Releasing Intrauterine System Utilization in Patients with Developmental Delays.

INTRODUCTION: Adolescent females with developmental delays (DDs) experience unique physical and emotional challenges related to menstruation. Providers often recommend hormonal medication for menstrual management. The objective of our study was to describe the utilization and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) in adolescents with DDs. METHODS: We utilized the Pediatric Health Information System to identify females aged 10-25 with DDs who underwent an LNG-IUS insertion between 2011 and 2020. Using a gynecologic procedure and diagnosis codes, we assessed indications for and complications of LNG-IUS use. We also evaluated early LNG-IUS removal. RESULTS: One thousand five hundred and sixty female patients with DDs underwent LNG-IUS insertion. LNG-IUS insertion under anesthesia was most commonly performed in patients with autism and Down syndrome, and unspecified menstrual issues were documented for 40% of the cohort. Perforation was observed in 11 patients (1%), and mechanical complications (malpositioned IUS or lost threads) were observed in 23 patients (1%). DISCUSSION: This is the largest analysis of LNG-IUS use in patients with DDs to our knowledge and shows the utilization of LNG-IUS in patients with DDs. We provide descriptive information that providers can use to accurately advise their patients with DDs on the risks and benefits of LNG-IUS use for menstrual management.

Levonorgestrel-Releasing Intrauterine System Improves Menorrhagia-Related Quality of Life in Patients with Symptomatic Adenomyosis.

Levonorgestrel-releasing intrauterine system (LNG-IUS) relieves dysmenorrhea and heavy menstrual bleeding (HMB) in adenomyosis. However, its efficacy on health-related quality of life (HR-QOL) in patients with symptomatic adenomyosis remains unclear. The menorrhagia multi-attribute scale (MMAS), which measures HR-QOL improvement through the treatment of HMB, has never been used for evaluating menorrhagia-specific HR-QOL in patients with symptomatic adenomyosis. Hence, this study aimed to investigate the efficacy of LNG-IUS in improving menorrhagia-specific HR-QOL in these patients using the MMAS. The participants were diagnosed by magnetic resonance imaging. We also assessed the relationships between menorrhagia-specific HR-QOL, blood hemoglobin levels, and the degree of dysmenorrhea before and during LNG-IUS treatment. The LNG-IUS treatment improved the menorrhagia-specific HR-QOL more effectively in incipient type adenomyosis than in advanced type adenomyosis. The efficacy of LNG-IUS treatment on dysmenorrhea evaluated by the visual analog scale score tended to be better in the incipient type than in the advanced type. By the treatment of LNG-IUS, the blood hemoglobin level was not improved in the advanced type but in the incipient type. Furthermore, dysmenorrhea and HMB-related anemia were associated with HR-QOL impairment, and LNG-IUS treatment may improve the HR-QOL by relieving the symptoms. In conclusion, the effectiveness of LNG-IUS on HR-QOL is decreased by advanced adenomyosis. Thus, magnetic resonance imaging use should be reinforced to predict LNG-IUS efficacy in improving the HR-QOL of patients with adenomyosis.

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

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

Vaginal micronized progesterone versus the levonorgestrel-releasing intrauterine system for treatment of non-atypical endometrial hyperplasia: A randomized controlled trial.

OBJECTIVE: To compare the efficiency of vaginal micronized progesterone (VMP) with the levonorgestrel-releasing intrauterine system (LNG-IUS) in patients with non-atypical endometrial hyperplasia. A validated Menorrhagia Impact Questionnaire (MIQ) was used to assess the quality of life before and after the procedure. METHODS: In this prospective trial, 144 women were randomly assigned to the VMP or LNG-IUS group. The primary endpoint was the regression rate of endometrial hyperplasia after 3 months of treatment. The protocol was approved by the institutional ethics committee and registered at ClinicalTrials.gov (NCT03992937). RESULTS: In all, 138 patients were analyzed. The regression rate was not significantly different between the groups (95.8% with LNG-IUS vs. 90.8% with VMP; P = 0.194). Differences between pre- and post-treatment MIQ scores were similar, except that better scores were obtained in the VMP group for the perception of the amount of blood loss (P = 0.035). CONCLUSION: VMP is as effective as the LNG-IUS as a local treatment of endometrial hyperplasia without atypia. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03992937.

Clinical evaluation of high-intensity focused ultrasound ablation combined with mifepristone and levonorgestrel-releasing intrauterine system to treat symptomatic adenomyosis.

OBJECTIVE: To evaluate the clinical efficacy of the combination of high-intensity focused ultrasound (HIFU), mifepristone, and levonorgestrel-releasing intrauterine system (LNG-IUS) in adenomyosis treatment. METHODS: HIFU treatment was performed in 123 patients with symptomatic adenomyosis who had refused treatment with gonadotropin-releasing hormone agonist (GnRH-a) at Anyang Maternal and Child Health Care Hospital. In the control group, 34 patients were treated with HIFU alone, 29 patients with HIFU combined with mifepristone, 10 patients with HIFU combined with LNG-IUS. In the study group, 50 patients were treated with HIFU combined with mifepristone and LNG-IUS. RESULTS: Uterine volume, dysmenorrhea pain score, menstruation volume score, and serum CA125 level were significantly lower after treatment with HIFU combined with mifepristone and LNG-IUS than before treatment (p < .05). Moreover, hemoglobin level was significantly higher than that before treatment (p < .05). After 24 months, the efficacy of HIFU combined with mifepristone and LNG-IUS was significantly higher than that of HIFU alone, HIFU combined with mifepristone or HIFU with LNG-IUS (p < .05). CONCLUSIONS: Combination therapy of HIFU, mifepristone, and LNG-IUS is an effective, safe, and inexpensive treatment for patients with symptomatic adenomyosis. This combination therapy demonstrates superior efficacy to treatment with HIFU alone, HIFU combined with mifepristone, and HIFU combined with LNG-IUS.