Levonorgestrel-releasing Intrauterine System Research Articles

Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems

This study uses data from nationwide Danish registries to assesses breast cancer risk with continuous use of levonorgestrel-releasing intrauterine systems, accounting for other hormonal exposures.

Treating endometrial hyperplasia (EH) post-tamoxifen treatment in breast cancer survivors: what are our options?

Tamoxifen is known to raise the risk of endometrial hyperplasia and cancer. There is virtually limited literature on how to handle Tamoxifen-induced endometrial hyperplasia (EH) in a breast cancer survivor. Levonorgestrel-releasing intrauterine system (LNG-IUS) has been explored as preventive strategies, but its impact on breast cancer recurrence especially in Progesterone receptor (PR)-positive patient is not clear. Aromatase Inhibitors (AIs) have shown beneficial results in EH after tamoxifen and their role should be explored in further trials.

Study finds association between levonorgestrel exposure, depression

A cohort study based on national data in Denmark has found a dose‐dependent association between use of levonorgestrel‐releasing intrauterine systems (LNG‐IUSs) for contraception and risk of incident depression. The study's investigators pointed out that the 1‐year absolute risks of depression in users of LNG‐IUSs were relatively small. Study results were published online July 10, 2024 in the American Journal of Psychiatry.

Efficacy of drugs treatment in patients with endometrial hyperplasia with or without atypia: A systematic review and network meta-analysis.

Endometrial hyperplasia (EH) is a hyperplastic endometrial lesion with irregular gland size, increased glands, and increased glandular interstitial ratio. During follow-up, some EH progressed further to endometrial cancer. It is crucial to provide timely treatment for EH and improve the overall prognosis of EH patients. We searched the PubMed, ClinicalTrials.gov., and Embase databases for studies published from their inception to March 31, 2023. The methodological quality of each study was evaluated in accordance with the Cochrane Collaboration's tool for assessing the risk of bias. The RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis statistical analysis; and the relative risk and 95% confidence interval along with the mean difference and 95% confidence interval, were used as evaluation indexes. We included 21 randomized controlled trials involving a total of 2276 women with EH, 6 studies were of high quality, and 15 were of moderate quality. The blinding of subjects and intervention providers was identified as the main source of potential bias. Six interventions were addressed in the network meta-analysis: medroxyprogesterone acetate (MPA), plus metformin, norethisterone (NET), levonorgestrel-releasing intrauterine system (LNG-IUD), megestrol acetate, and other drugs. In the direct meta-analysis, we found the probability of endometrial complete regression (CR) in the LNG-IUD group to be significantly higher than those in the NET. In the network meta-analysis, we found the probability of CR in the NET group to be significantly lower than those in the MPA and plus metformin groups, the probability of CR in the LNG-IUD group to be significantly higher than those in the NET, the probability of CR in the other drugs group to be significantly higher than those in the LNG-IUD. The NET group had the lowest incidences of endometrial complete regression, plus metformin could have a better outcome. According to the 21 randomized controlled trials included in this study, MPA is the most effective for EH endometrial outcome when applied as a single agent, while the combination of metformin can achieve a more significant effect.

Analysis of assisted reproductive outcomes in patients with atypical endometrial hyperplasia and early-stage endometrial cancer after fertility-sparing treatment.

To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment. This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent invitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate. The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant. For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes.

Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation combined with different drugs in the treatment of adenomyosis

Objectives To observe the therapeutic efficacy of high-intensity focused ultrasound (HIFU) combined with different pharmacological treatments for adenomyosis. Materials and methods A total of 126 patients with adenomyosis who underwent HIFU combined with pharmacological treatment were retrospectively reviewed. Patients were treated with either dienogest (DNG) (Group A, N = 38) or GnRH-a (Group B, N = 88) for three months after HIFU, and received levonorgestrel-releasing intrauterine systems (LNG-IUS) at the end of the third month. Visual Analog Scale (VAS) and Pictorial Blood Loss Assessment Chart (PBAC) scores were used for evaluating symptom improvement. Results After propensity score matching (1:2), 38 patients were included in Group A and 76 in Group B. All patients showed significant improvement in VAS and PBAC scores after HIFU, but the PBAC score of Group A was significantly higher than that of patients in Group B at 18 months [11.50 (1.00, 29.50) vs. 0.00 (0.00, 16.50), p < 0.01] and 24 months [4.00 (0.25, 27.75) vs. 0.00 (0.00, 12.75), p = 0.04] after HIFU. Furthermore, patients in Group B had a greater uterine volume reduction at 24 months after HIFU than that of patients in Group A [51.00 (27.00, 62.00) vs. 30.00 (17.00, 42.75, p = 0.02)]. However, the adverse effects in Group A were lower than those in Group B [7 (15.79) vs. 35 (46.05), p < 0.01]. No significant difference was observed in the recurrence rate between the two groups. Conclusions HIFU combined with DNG and LNG-IUS is a safe and effective treatment for patients with adenomyosis.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol

BackgroundAround 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes.MethodsThis study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence.Ethics and disseminationThe protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association’s Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal.ConclusionsProspective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH.Trial registration numberChinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

Preventing recurrence of endometriosis-related pain by means of long-acting progestogen therapy: the PRE-EMPT RCT.

Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Recurrence of symptoms following an operation is common. Although hormonal treatment can reduce this risk, there is uncertainty about the best option. To evaluate the clinical and cost-effectiveness of long-acting progestogen therapy compared with the combined oral contraceptive pill in preventing recurrence of endometriosis-related pain and quality of life. A multicentre, open, randomised trial with parallel economic evaluation. The final design was informed by a pilot study, qualitative exploration of women's lived experience of endometriosis and a pretrial economic model. Thirty-four United Kingdom hospitals. Women of reproductive age undergoing conservative surgery for endometriosis. Long-acting progestogen reversible contraceptive (either 150 mg depot medroxyprogesterone acetate or 52 mg levonorgestrel-releasing intrauterine system) or combined oral contraceptive pill (30 µg ethinylestradiol, 150 µg levonorgestrel). The primary outcome was the pain domain of the Endometriosis Health Profile-30 questionnaire at 36 months post randomisation. The economic evaluation estimated the cost per quality-adjusted life-years gained. Four hundred and five women were randomised to receive either long-acting reversible contraceptive (N = 205) or combined oral contraceptive pill (N = 200). Pain scores improved in both groups (24 and 23 points on average) compared with preoperative values but there was no difference between the two (adjusted mean difference: -0.8, 95% confidence interval -5.7 to 4.2; p = 0.76). The long-acting reversible contraceptive group underwent fewer surgical procedures or second-line treatments compared with the combined oral contraceptive group (73 vs. 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). The mean adjusted quality-adjusted life-year difference between two arms was 0.043 (95% confidence interval -0.069 to 0.152) in favour of the combined oral contraceptive pill, although this cost an additional £533 (95% confidence interval 52 to 983) per woman. Limitations include the absence of a no-treatment group and the fact that many women changed treatments over the 3 years of follow-up. Use of telephone follow-up to collect primary outcome data in those who failed to return questionnaires resulted in missing data for secondary outcomes. The COVID pandemic may have affected rates of further surgical treatment. At 36 months, women allocated to either intervention had comparable levels of pain, with both groups showing around a 40% improvement from presurgical levels. Although the combined oral contraceptive was cost-effective at a threshold of £20,000 per quality-adjusted life-year, the difference between the two was marginal and lower rates of repeat surgery might make long-acting reversible contraceptives preferable to some women. Future research needs to focus on evaluating newer hormonal preparations, a more holistic approach to symptom suppression and identification of biomarkers to diagnose endometriosis and its recurrence. This trial is registered as ISRCTN97865475. https://doi.org/10.1186/ISRCTN97865475. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/114/01) and is published in full in Health Technology Assessment; Vol. 28, No. 55. See the NIHR Funding and Awards website for further award information. The NIHR recognises that people have diverse gender identities, and in this report, the word 'woman' is used to describe patients or individuals whose sex assigned at birth was female, whether they identify as female, male or non-binary.

Safety profile of levonorgestrel intrauterine system: Analysis of spontaneous reports submitted to FAERS

The levonorgestrel-releasing intrauterine system (LNG-IUS) is an established, long-acting contraceptive option. With the widespread use of the LNG-IUS, drug-reported adverse events (AEs) have also garnered significant attention. In this study, we conducted a real-world analysis using the FDA's Adverse Event Reporting System (FAERS) database to assess the incidence of AEs associated with LNG-IUS use. Data from FAERS spanning from 2004Q1 to 2024Q1 were reviewed, with a focus on reports in which LNG-IUS was the primary suspected and secondary suspect drug. Signal detection was carried out utilizing Standardized MedDRA Queries (SMQ) and Preferred Terms (PT), with reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) employed to identify Signals of Disproportionate Reporting (SDR) for AEs. A positive SDR was defined when all three methods indicated significance. Analysis of 13 SMQs revealed notable SDRs in ear and eye disorders, cardiac arrhythmias, and lipodystrophy. Of the 61 suspected SDRs identified at the PT level, nearly half were not previously documented in labeling. Key potential signals of AEs associated with LNG-IUS use included increased heart rate, papilledema, idiopathic intracranial hypertension, cervical dysplasia, ruptured ovarian cyst, and uterine embedment and perforation. The findings underscore the importance of signal detection using FAERS data for identifying safety concerns related to LNG-IUS. Long-term observational studies are warranted to confirm and further elucidate these potential safety signals.

The Effect of the Levonorgestrel-Releasing Intrauterine System on Myometrial Blood Flow in Patients With Heavy Menstrual Bleeding.

Background Abnormal uterine bleeding constitutes a vexing issue among female patients, substantially impacting their quality of life. Surgical interventions, particularly hysterectomy, contribute to the psychological, physical, and financial burden on families and, by extension, the healthcare system. Levonorgestrel-releasing intrauterine system (LNG-IUS) represents a conservative management approach and emerges as a beneficial option for affected patients. The present study aims to elucidate color Doppler changes in the uterine artery pre- and post-LNG-IUS insertion. Objective The primary objectives encompass an investigation into the variations in Doppler indices (resistance index (RI) and pulsatility index (PI)) within the arcuate and radial branches of the uterine artery, as well as the assessment of endometrial thickness before LNG-IUD insertion, at three months, and six months post-insertion. Secondary outcomes include evaluating changes in pictorial blood assessment chart (PBAC) scores before insertion, at three months, and at six months after LNG-IUS insertion. Methods A cross-sectional study was conducted at the Department of Obstetrics and Gynecology at All India Institute Of Medical Sciences (AIIMS), Nagpur. A cohort of 25 women underwent LNG-IUS insertion. The endometrial cavity, RI, and PI of both arcuate and radial arteries were assessed before LNG-IUS insertion and at three and six months after insertion. Results The PI of the arcuate artery exhibited minimal alteration over the six-month duration, with a p-value of 0.43. Conversely, the RI demonstrated a statistically significant increase over the same period (p = 0.03). Conversely, the radial artery exhibited no statistically significant changes in either PI or RI (p = 0.39 or 0.13, respectively). Conclusion Following six months of LNG-IUS utilization, a substantial reduction in endometrial thickness and menstrual flow was observed, concomitant with an improvement in hemoglobin levels. Notably, the PI of both the arcuate and radial arteries demonstrated no significant change. Although the RI of the arcuate artery increased, its clinical relevance may be limited. Consequently, the observed reduction in menstrual bleeding cannot conclusively be ascribed to diminished blood flow in uterine arteries.

Levonorgestrel intrauterine system versus dienogest effect on quality of life of women with deep endometriosis: a randomized open-label clinical trial

ABSTRACT Women with deep infiltrating endometriosis (DIE) can benefit from the use of progestins. Our aim is to explore if levonorgestrel-releasing intrauterine system (LNG-IUS) non inferior to dienogest (DNG) in improving deep endometriosis women’s quality of life (QoL). This randomized open-label clinical trial included forty women with DIE assessed using clinical history and physical examination, transvaginal ultrasonography and magnetic resonance of the pelvis without any previous surgical treatment, with two treatments arms. The two groups underwent a 3-month washout of hormonal treatments, and then received either DNG or LNG-IUS for 6 months. QoL was assessed prior to and 6 months after the intervention, using the SF36 and the EHP30. DNG and LNG-IUS showed an increase on all domains of the SF36 (p < .001). There was no difference between treatments on the improvement observed (p > .05 for all domains). DNG and LNG-IUS, also, showed improvement on all domains of EHP30 (p < .001), except “relationship with children” and “feelings about pregnancy.” However, there was no statistical difference between treatments for all sections scores (p > .05). The treatment of deep endometriosis symptoms using either DNG or LNG-IUS in women with no prior surgical treatment is associated with improvement in QoL. Trial Registration Number: This trial is registered on “The Brazilian Registry of Clinical Trials (ReBECID: RBR-8fjx2jp),” that is part of Primary Registries in the WHO Registry Network, under the title: “Dienogest versus Levonorgestrel IUS on deep endometriosis patient´s QoL without surgery” on June 14, 2021; https://ensaiosclinicos.gov.br/rg/RBR-8fjx2jp.

Biological characteristics related to treatment effects of the levonorgestrel-releasing intrauterine system on adenomyosis-associated dysmenorrhoea

Research questionTo investigate the correlations among the biological expression of steroid receptors, fibrosis levels in adenomyotic lesions, and the treatment effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) on alleviation of dysmenorrhea. DesignIn this retrospective cohort study, 125 women with adenomyosis who underwent hysterectomy were included. The tissue samples were collected from 41 patients who had been treated by the LNG-IUS prior to surgery and these patients were further categorized into an effective group (n = 18) and a failure group (n = 23) according to their self-reported relief from dysmenorrhea after 6-month treatment. The expression levels of estrogen receptor-α (ER-α), progesterone receptor (PR), and the extent of fibrosis levels in the adenomyotic lesions were measured by immunohistochemistry and Masson's trichrome staining respectively. ResultsPatients in the failure group demonstrated lower expression levels of ER-α and PR and more pronounced fibrosis in the stroma of adenomyotic lesions compared to those in the effective group. In the glandular epithelium of lesions, ER-α expression was significantly reduced in the failure group, whereas no notable difference in PR expression was observed. Notably, the staining intensity of ER-α in the stroma of the lesions was found to have the strongest positive correlation with the degree of symptom alleviation for dysmenorrhea (r=0.47) with an area under the curve of 0.894 for prediction. ConclusionsThe findings suggest that the reduced expressions of steroid receptors in adenomyotic lesions especially ER-α in the stroma were associated with an increased likelihood of treatment failure of LNG-IUS in alleviating dysmenorrhea.

Association Between Intrauterine System Hormone Dosage and Depression Risk.

The authors compared the associated risk of incident depression between first-time users of low-, medium-, and high-dose levonorgestrel-releasing intrauterine systems (LNG-IUSs). This national cohort study was based on Danish register data on first-time users of LNG-IUSs, 15-44 years of age, between 2000 and 2022. Cox regression and a G-formula estimator were used to report 1-year average absolute risks, risk differences, and risk ratios of incident depression, defined as initiation of an antidepressant or receipt of a depression diagnosis, standardized for calendar year, age, education level, parental history of mental disorders, endometriosis, menorrhagia, polycystic ovary syndrome, dysmenorrhea, leiomyoma, and postpartum initiation. In total, 149,200 women started using an LNG-IUS, among whom 22,029 started a low-dose one (mean age, 22.9 years [SD=4.5]), 47,712 a medium-dose one (mean age, 25.2 years [SD=6.2]), and 79,459 a high-dose one (mean age, 30.2 years [SD=5.6]). The associated subsequent 1-year adjusted absolute risks of incident depression were 1.21% (95% CI=1.06-1.36), 1.46% (95% CI=1.33-1.59), and 1.84% (95% CI=1.72-1.96), respectively. For the users of high-dose LNG-IUSs, the risk ratios were 1.52 (95% CI=1.30-1.74) and 1.26 (95% CI=1.10-1.41) compared with users of the low- and medium-dose LNG-IUSs, respectively. For users of medium-dose LNG-IUSs, the risk ratio was 1.21 (95% CI=1.03-1.39) compared with users of low-dose LNG-IUSs. First-time use of an LNG-IUS was positively associated with incident depression in an LNG-dose-dependent manner across low-, medium-, and high-dose LNG-IUSs. Although the observational design of the study does not permit causal inference, the dose-response relationship contributes to the body of evidence suggesting a relationship between levonorgestrel exposure and risk of depression.

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.

A Case in Which Flexible Hysterofiberscopic Observation Was Useful for Removal of the Arm of a Levonorgestrel-releasing Intrauterine System That Had Pierced the Cervical Wall.

A Case in Which Flexible Hysterofiberscopic Observation Was Useful for Removal of the Arm of a Levonorgestrel-releasing Intrauterine System That Had Pierced the Cervical Wall.

Fertility-sparing re-treatment for endometrial cancer and atypical endometrial hyperplasia patients with progestin-resistance: a retrospective analysis of 61 cases

ObjectiveThis study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility.MethodsOur study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3–4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy.ResultsOverall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages.ConclusionGnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.

Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

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

Safety of Progestogen Hormonal Contraceptive Methods during Lactation: An Overview.

Breastfeeding is a process for not only nourishing infants but also for building a unique emotional bond between mother and child. Therefore, the ideal contraception during lactation should not affect lactation (milk composition, milk volume) and offspring development. This study aims to analyze the literature on the safety of progestogen hormonal contraceptive methods during lactation. We conducted a thorough search across various databases, including the National Library of Medicine (PubMed), and the Cochrane Database, Drugs and Lactation Database (LactMed). Our search utilized specific phrases such as: "lactation" and "breastfeeding" and "oral contraception" with "drospirenone" or "desogestrel", with "subcutaneous etonogestrel implant" or "etonogestrel implant", with "levonorgestrel-releasing intrauterine system", and "emergency contraception", with "levonorgestrel" or "ulipristal acetate". Based on published scientific reports, progestogen hormonal contraceptives can be considered a relatively safe solution for women desiring to continue feeding their infant with their milk while using hormonal contraception. It is important to seek guidance on selecting the best contraception method based on the latest medical knowledge, tailored to the individual needs and clinical circumstances of each woman and place of residence. A woman should always be informed of the potential risks of such a treatment and then allowed to make her own decision based on the knowledge received from a specialist.

Efficacy of hysteroscopic levonorgestrel‑releasing 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).

Comparative analysis of endometrium after using levonorgestrel-releasing intrauterine system and copper intrauterine device

BACKGROUND: To date, the risks of pelvic inflammatory diseases, including chronic endometritis, associated with the use of various intrauterine contraceptives, have remained debatable. AIM: The aim of this study was to conduct a comparative analysis of the endometrial status in women of reproductive age after the use of copper- or levonorgestrel-releasing intrauterine device. MATERIALS AND METHODS: Morphological and immunohistochemical studies of endometrial biopsies obtained by aspiration Pipelle biopsy were performed after intrauterine device extraction in 18 patients who used a copper-containing intrauterine device and in 12 women who used the levonorgestrel-releasing intrauterine device Mirena. Monoclonal mouse antibodies to CD20, CD138, and α-smooth muscle actin (DAKO, Denmark) were used. Criteria for inclusion of patients in the study are reproductive age, use of an intrauterine device for five years, absence of complications associated with the intrauterine device during its use. Exclusion criteria are a history of pelvic inflammatory diseases, sexually transmitted infections, habitual miscarriage, two or more intrauterine interventions. RESULTS: After using a copper-containing intrauterine device, signs of chronic inflammation were found in the endometrium such as cytogenic stroma fibrosis with pronounced infiltration by inflammatory cells, positive expression of CD138 (33.3% of observations), CD20 (88.9% of observations with an average number of 27.4 ± 5.7), α-smooth muscle actin (up to 70% of the cytogenic stroma area), and the presence of lymphatic follicles consisting of B lymphocytes (33.3% of observations). During the use of the levonorgestrel-releasing intrauterine device, decidual transformation of cytogenic stroma cells, as well as secretion and atrophy of the glandular epithelium, were found in the endometrium. CD20-positive cells were detected in five out of 12 cases (41.6% of observations with an average number of 12.8 ± 4.6). Expression of CD138 and α-smooth muscle actin was not detected in any of the cases. CONCLUSIONS: The use of a copper-containing intrauterine device is associated with a high risk of developing chronic endometritis. The absence of signs of chronic inflammation in the endometrium after the use of a levonorgestrel-releasing intrauterine device is probably due to the protective effect of levonorgestrel on the uterine mucosa. Thus, levonorgestrel-releasing intrauterine devices, in comparison with copper-containing intrauterine devices, have a favorable safety profile relative to the endometrium and can be recommended for women of reproductive age, including those who have not given birth.