Levonorgestrel-releasing Intrauterine System Research Articles

Ulipristal acetate versus levonorgestrel-releasing intrauterine system for heavy menstrual bleeding: the UCON randomised controlled trial and mechanism of action study

Background Heavy menstrual bleeding affects one in four women and negatively impacts quality of life. The levonorgestrel-releasing intrauterine system is an effective long-term treatment but is discontinued by many due to unpredictable bleeding, or adverse effects. The selective progesterone receptor modulator ulipristal acetate is used to treat symptomatic fibroids but long-term efficacy for the symptom of heavy menstrual bleeding, irrespective of presence of fibroids, is unknown. Objectives To determine whether ulipristal acetate is more effective at reducing the burden of heavy menstrual bleeding than levonorgestrel-releasing intrauterine system after 12 months of treatment in women with and without fibroids. We investigated mechanism of action of ulipristal acetate in a subset of 20 women. Design Randomised, open-label, parallel group, multicentre trial with embedded mechanistic study. Setting Ten UK hospitals. Participants Women with heavy menstrual bleeding aged 18 and over with no contraindications to levonorgestrel-releasing intrauterine system or ulipristal acetate. Interventions Three 12-week treatment cycles of 5 mg ulipristal acetate daily, separated by 4-week treatment-free intervals, or continuous levonorgestrel-releasing intrauterine system following allocation in a 1 : 1 ratio using a web-based minimisation procedure. Main trial outcome measures Primary outcome was quality-of-life measured by menorrhagia multi-attribute scale at 12 months. Secondary outcomes included menstrual bleeding and patient satisfaction. Impact on fibroid size, endometrial appearance and liver function was also collected. Mechanistic study outcome Cellular markers for endometrial cell structure and function, determined from endometrial biopsies; volume of uterus and fibroids and microcirculation parameters were determined from magnetic resonance images. Results Sample size was increased from 220 to 302 as a result of temporary halt to recruitment due to concerns of ulipristal acetate hepatoxicity. Subsequent withdrawal of ulipristal acetate and the COVID-19 pandemic led to a premature closure of recruitment, with 118 women randomised to each treatment and 103 women completing 12-month menorrhagia multi-attribute scale scores prior to this point. Primary outcome scores substantially improved in both arms, but at 12 months there was no evidence of a difference between those receiving three cycles of ulipristal acetate [median score category: 76–99, interquartile range (51–75 to 100), n = 53] and levonorgestrel-releasing intrauterine system [median score category: 76–99, interquartile range (51–75 to 100), n = 50; adjusted odds ratio 0.55, 95% confidence interval 0.26 to 1.17; p = 0.12]. Rates of amenorrhoea were much higher in those allocated ulipristal acetate compared with the levonorgestrel-releasing intrauterine system (12 months: 64% vs. 25%, adjusted odds ratio 7.12, 95% confidence interval 2.29 to 22.2). There was no evidence of a difference in other participant-reported outcomes. There were no cases of endometrial malignancy and no hepatotoxicity due to ulipristal acetate use. Mechanistic study results Ulipristal acetate produced a reversible reduction in endometrial cell proliferation, as well as reversible alteration of other endometrial cellular markers. Ulipristal acetate did not produce a reduction in the volume of the uterus irrespective of coexisting fibroids, nor an effect on uterine microvascular blood flow. Limitations The urgent safety measures and premature closure of recruitment impacted final sample size. Conclusions We found no evidence of a difference in quality of life between the two treatments, but ulipristal acetate was superior to levonorgestrel-releasing intrauterine system at inducing amenorrhoea. Ulipristal acetate currently has restricted availability due to concerns regarding hepatotoxicity. Future work There is a need to develop new, safe, effective and fertility-sparing medical treatments for heavy menstrual bleeding. The observed acceptability and effectiveness of ulipristal acetate warrants further research into the selective progesterone receptor modulator class of pharmacological agents. Study registration This trial is registered as ISRCTN 20426843.

Risk of Hysterectomy After Endometrial Ablation: A Systematic Review and Meta-analysis

ABSTRACT A common gynecological problem for approximately 30% of women at reproductive age in European countries is heavy menstrual bleeding (HMB). Although hysterectomy is a highly successful treatment for this benign problem, it also risks serious complications due to its nature as a major operation. Less invasive HMB treatment options include insertion of a levonorgestrel-releasing intrauterine system, medical treatment (such as tranexamic acid and oral contraceptive pill), or endometrial ablation (which aims to destroy endometrial tissue and the superficial myometrium to reduce/stop menstrual bleeding). Endometrial ablation failure may result in the objective outcome of hysterectomy. This meta-analysis and review aimed to assess hysterectomy risk following nonresectoscopic endometrial ablation treatment to improve understanding and HMB patient counseling. Various nonresectoscopic ablation techniques versus their associated hysterectomy rates were investigated, and subgroup analyses were performed. Following a comprehensive and thorough search process of the MEDLINE, CENTRAL, and EMBASE databases, 53 articles ultimately met the inclusion criteria for inclusion in the systematic review. Between 1992 and 2017, in the included studies, 48,071 patients underwent endometrial ablation. A high risk of bias was found in 13 studies (mainly due to selection or reporting bias), whereas 12 studies maintained low risk of bias. However, exclusion of the 13 high-risk studies for a subgroup analysis yielded similar results to the original meta-analysis. Results of the analysis indicated a consistently increasing post–endometrial ablation hysterectomy, with 2% increments annually between 1 and 5 years following the procedure, rising to 4.3% after 1 year and 12.4% after 5 years. In 2 studies, a post–10-year follow-up found a mean hysterectomy rate of 21.3%. Between both various study designs and the different varieties of devices used, no major differences in hysterectomy rates were found, respectively. Limitations of the review include a high risk for heterogeneity found among studies in almost all analyses utilized by this analysis. Publication bias and methodological issues (variation of population size and study type) lent to the heterogeneity. Because of this variation, the authors performed analyses of subgroups with different study designs. In addition, of the 53 studies included, 15 of them included fewer than 50 participants, which was corrected in this analysis via an inverse variance. Overall, the study indicated that hysterectomy risk following endometrial ablation increases from 4.3% at the 1-year mark to 12.4% at the post–5-year mark. Neither differences in nonresectoscopic endometrial ablation techniques nor study design seemed to affect hysterectomy rates. This systematic review's data can be applied to clinical practice and used for counseling patients about hysterectomy risks within 5 years of endometrial ablation.

Hysteroscopic suture of levonorgestrel-releasing intrauterine system: learning curve for in vitro simulation training.

To simulate hysteroscopic suturing in vitro and analyze the learning curve of gynecologists with different experience levels. Three gynecologists were trained on uterine models in a circulating water box. The posterior uterine wall was sutured 10 times under hysteroscopy for 5 consecutive days, and the time of each suture procedure was recorded. Doctors A, B, and C completed 50 posterior uterine sutures. After Dr. C completed 50 sutures on the posterior wall, he added 50 sutures on the anterior wall (Group D). The mean suturing time was 71.54 ± 68.158 s in Group A, 50.10 ± 28.060 s in Group B, 34.04 ± 10.457 s in Group C, and 30.38 ± 8.734 s in Group D. The difference between Groups C and B and between Groups B and A was statistically significant. There was no statistically significant difference between Groups C and D. Simulation curves were created using the number of features as the abscissa and cumulative sum as the coordinate, with peak curves of 19, 27, and 18 cases for Group A, B, and C, respectively. Doctors with experience in single-hole laparoscopic surgery or hysteroscopic suture surgery can significantly shorten the hysteroscopic suturing time.

Preservation of the reproductive health of military women: global experience and realities of Ukraine

A review of world literature and Ukrainian researches on the most common requests to gynecologists among military women, on the structure of pathology and treatment methods was made. Special attention is paid to the hormonal contraception, namely combined oral contraceptives (COCs) in the usual and continuous regime (avoiding the hormone-free interval) and the levonorgestrel-releasing intrauterine systems (LNG-IUDs).Cases of global practice of using COCs in extended regimen were considered, which showed that 47.2% of 1156 women chose a prolonged regimen of COCs, the main reason for this was the desire to avoid symptoms associated with menstruation. We consider this option very positive for military women, because some studies show that military women who took COCs in a continuous regimen were almost twice as favorable to their reception as those who used them in a regular mode.The positive aspects of the LNG-IUDs use in military women are presented, as a factor in the prevention of abnormal uterine bleeding, reducing the risk of iron deficiency in case of possible blood loss, and reducing the intensity of dysmenorrhea as a negative factor in the military conditions.Ways to increase compliance between a gynecologist and a military woman are also considered, using the example of global studies, which prove that insufficient awareness of patients about the possible ways and positive effects of using COCs in extended regimen reduced patients’ commitment to choosing new regimens.Conclusions. In today’s realities, the gynecological service in our country faces a number of new problems that require a strategic approach and solution. World practice and national studies prove that stress-induced hormonal disorders in military women, such as abnormal uterine bleeding, menstrual cycle disorders, dysmenorrhea, are negative factors in combat conditions, require the attention and resolution by doctors. One of the options for solving this problem can be the appointment of COCs according to the usual and extended scheme or appointment of LNG-IUDs.

The impact of self-administered vaginal isonicotinic acid hydrazide (INH) administration 12 hours prior to levonorgestrel-releasing intrauterine system in women delivered only by elective cesarean section: A randomized double blinded clinical trial

The impact of self-administered vaginal isonicotinic acid hydrazide (INH) administration 12 hours prior to levonorgestrel-releasing intrauterine system in women delivered only by elective cesarean section: A randomized double blinded clinical trial

LEVONORGESTREL RELEASING INTRAUTERINE SYSTEM (MIRENA) FOR ABNORMAL UTERINE BLEEDING- A USEFUL TOOL IN THE COVID TIMES

Objectives: To assess the effectiveness of the Levonorgestrel-releasing intrauterine system (LNG-IUS) in improving heavy menstrual bleeding (HMB) and evaluate satisfaction rates among women with heavy menstrual bleeding, treated with LNG–IUS. Material and methods: This prospective observational study with a one-year follow-up included 73 women of reproductive age 20 – 50 years with complaints of heavy menstrual bleeding (HMB). They presented to the Gynae ward and the outpatient department (OPD) of Khyber Teaching Hospital, Peshawar, Pakistan. Patients with more than 3 cm fibroids, pelvic inflammatory disease, bleeding of unknown cause, and any known pelvic malignancy were excluded. LNG-IUS (Mirena) was inserted in OPD routinely and in Operation Theater under anesthesia where the cervix could not be dilated. Patients were followed up in OPD at one month, 3 months, six months, and one year. Improvement in symptoms, satisfaction level, and Hemoglobin (Hb) before and after the procedure was documented on a Proforma. RESULTS: There was a progressive resolution in the amount of bleeding in patients followed at 1-month, 3-month, six months, and one year. The satisfaction rate was 92%. There was an improvement in Hb in 97% of patients. Only 04 out of 73 patients needed a hysterectomy. CONCLUSION: Levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective and tolerated treatment option for abnormal uterine bleeding. In the Covid times, it proved to be an effective first-line management of AUB. We recommend its use after careful selection of patients and also recommend a good counseling session before its use. Keywords: Abnormal uterine bleeding, heavy menstrual bleeding, LNG – IUS.

Metformin versus levonorgestrel-releasing intrauterine system in the management of endometrial hyperplasia: a randomized clinical trial

BackgroundEndometrial hyperplasia is one of the common causes of bleeding in perimenopausal women. Variable treatment options aim to induce regression. The current study evaluated the regression rate of endometrial hyperplasia after treatment with levonorgestrel intrauterine system (LNG- IUS) versus Metformin.MethodsThis randomized clinical trial was conducted at the obstetrics and gynecology department of Suez Canal University hospital. We recruited women diagnosed with endometrial hyperplasia without atypia. Patients were allocated into two groups. Group one included patients treated with levonorgestrel-releasing intrauterine system and group two treated with Metformin. The rate of regression of hyperplasia in both groups after six months of intervention was the main outcome measure.ResultsSignificant regression of hyperplasia was noted in the LNG-IUS group (96% versus 64%, p-value 0.009). There was a significant decrease in the endometrial thickness after treatment in both groups (17.65 ± 4.62 and 5.3 ± 2.01 in the LNG- IUS with a p-value < 0.001) (19.57 ± 6.84 and 11.22 ± 7.51 in the metformin group with a p-value < 0.001). Factors that correlated with the Δ endometrial thickness included parity in the LNG- IUS group (p-value 0.019) and age and BMI in the metformin group (p-value 0.043 and 0.004 respectively).ConclusionMetformin had a regressive effect on endometrial hyperplasia; however, it was not significant as that achieved with the levonorgestrel intrauterine system.Trial registrationsPACTR201908498370196.Date of registration: 21/8/2019.Date of first patient enrollment: 25/8/2019.URL: https://pactr.samrc.ac.za/Researcher/TrialRegister.aspx?TrialID=9335

Extended Use of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) 52 mg: A Population Pharmacokinetic Approach to Estimate In Vivo Levonorgestrel Release Rates and Systemic Exposure Including Comparison With Two Other LNG-IUSs

ABSTRACT With over 30 years of use, levonorgestrel-releasing intrauterine systems (LNG-IUSs) have proven to be highly effective methods of contraceptives. The active ingredient in LNG-IUS, levonorgestrel (LNG), is released directly into the uterine cavity, which causes suppression of endometrial maturation and thickened cervical mucus. A variety of LNG-IUS options exhibit well-established safety profiles and efficacy, providing anywhere between 2 and 18 times lower systemic exposure when compared with LNG-containing pills or implants. Patient-centered decision-making regarding product choice may be encouraged through standardized comparisons of LNG release and exposure during the time of their respective usage periods. Evaluation of the efficacy, safety, and PK of extended Mirena use from beyond 5 years to the conclusion of 8 years was designed in the Mirena Extension Trial (MET), thereby facilitating comparisons with LNG-IUS 19.5 mg and LNG-IUS 13.5 mg. Using validated liquid chromatography-tandem mass spectrometry methods and SHBG concentrations, the authors determined concentrations of plasma LNG levels. Dichloromethane was used for extracting residual LNG from the elastomer material from removed IUS devices, which was then quantified via liquid chromatography and external calibration on a reversed-phase column. Although previous models used measured LNG and SHBG (serum) concentrations, the population pharmacokinetics (popPK) allows for a uniform method of comparison among different pharmacologic studies. The popPK approach allows for a reliable estimates of in vivo LNG exposure and release during the entirety of the 8-year use period. The MET enrolled premenopausal women aged 18–35 years for a multicenter, single-arm study regarding patients who had used LNG-IUS 52 mg for the last 4.5–5 years for up to 8 years. The study took place from December 22, 2016 to May 28, 2021 throughout 54 US centers, with the primary outcome of contraceptive efficacy and failure rate. Participants each provided written, informed consent. Study strengths of the popPK approach included its robust methodology, its ability to provide in vivo release rate estimates, a stepwise demo of model suitability from use years 6 to 8, model-based estimation of unbound LNG, and the ability to provide estimates for both population and individual PK profiles from sparse available sampling. Limitations include the possibility of findings being group effects possibly inapplicable to all LNG-IUS users. In addition, the data fail to provide local endometrial and cervical LNG concentrations due to the systemic nature of the LNG exposure. Finally, the popPK Mondale should not be used for theoretical question addressing (such as creating rate release estimates outside of available data sets). In conclusion, a broad data set indicates that reliable LNG exposure is delivered by 8-year popPK and release models for up to 7 years of LNG-IUs 52 mg use. Efficacy is data-supported for 6–8 years of use, with constant LNG release throughout this time frame. Systemic LNG exposure from LNG-IUD 52 mg proved both comparable to other LNG-IUS devices and significantly lower than oral and implanted LNG-containing contraceptives.

The role of FIGO-PALM pathologies in heavy menstrual bleeding resistant to levonorgestrel-releasing intrauterine system (Mirena®) treatment

Objectives: To evaluate of the indications requiring surgical treatment after Levonorgestrel-Releasing Intrauterine System (LNG-IUS) (Mirena®) treatment due to heavy menstrual bleeding. Methods: This retrospectively designed study was created with 72 patients who applied to the university hospital gynecology outpatient clinics between January 2018 and April 2019 and were diagnosed with heavy menstrual bleeding and received LNG IUS (Mirena®) for treatment. Results: Surgery was not performed in 60 (83.33%) patients who had heavy menstrual bleeding and underlying organic pathology (FIGO-PALM group) These patients were treated with LNG-IUS. However, in 12 (16.67%) patients, LNG-IUS was removed and surgery was performed due to resistance to treatment within an average of 10.2 ± 8.0 months. There was no difference between the groups in terms of age, gravida, parity, body mass index and endometrial thickness p &amp;gt; 0.05 for all parameters), but the mean hemoglobin value in the surgical group was found to be significantly lower than the group without it (8.9 ± 1.2 g/dL vs 11 ± 1.6 g/dL, p = 0.03) In the surgical group, the median diameters of leiomyoma and myoma compressing the endometrium were found to be significantly higher (44 mm vs 34 mm, p = 0.03 and 42 mm vs 33 mm, p = 0.04; respectively). Conclusions: LNG-IUS (Mirena®) is a popular and effective treatment option for heavy menstrual bleeding. The necessity of surgical treatment due to resistance to LNG-IUS revealed that the underlying organic pathologies in these patients should be determined precisely and effective treatment options should be carefully selected before LNG-IUS is inserted.

P-751 Comparing levonorgestrel intrauterine system versus hysteroscopic niche resection in women with postmenstrual spotting related to a niche in the uterine caesarean scar

Abstract Study question To compare the effectiveness of levonorgestrel-releasing intrauterine system (LNG-IUS 52mg) with hysteroscopic niche resection in the reduction of niche-related postmenstrual spotting. Summary answer In women with niche-related postmenstrual spotting, LNG-IUS did not more often reduce spotting days with 50% at 6th month than hysteroscopic niche resection. What is known already Both Levonorgestrel intrauterine system (LNG-IUS) and hysteroscopic niche resection are widely implemented to reduce niche-related postmenstrual spotting. The study aimed to compare the effectiveness of LNG-IUS 52mg with hysteroscopic niche resection in the reduction of niche-related postmenstrual spotting. Study design, size, duration A randomised, open-label, controlled trial conducted at one medical center in Shanghai, China. From September 2019 to January 2022, we randomised 208 women to LNG-IUS (N = 104) or hysteroscopic niche resection (N = 104).The primary outcome was reduction of postmenstrual spotting at 6th month after randomisation, defined as percentage of women with a reduction of at least 50% in spotting days from baseline. Efficacy and safety were assessed by an intention-to-treat analyses. Participants/materials, setting, methods Women with symptoms of postmenstrual spotting after CS, with a niche depth of at least 2 mm and residual myometrium of at least 2.2mm on Magnetic Resonance Imaging (MRI), and no intention to conceive within the next year were randomly assigned to treatment with LNG-IUS 52mg or a hysteroscopic niche resection. Main results and the role of chance At 6th month follow-up, a 50% reduction of spotting had occurred in 78.4% (80/102) women in the LNG-IUS group and 73.1% (76/104) women in the hysteroscopic niche resection group (RR = 1.07, [95%CI 0.92-1.25]; P = 0.370). Spotting reduced over time (Ptrend=0.001), with a stronger reduction in the LNG-IUS group (P = 0.001), while there was also a significant interaction between time and treatment (P = 0.007). From nine months onwards, reduction of spotting occurred significantly more after LNG-IUS than hysteroscopic niche resection (9th month 89.2% vs. 72.1%, RR = 1.24, [95% CI 1.08-1.42]; 12th month 90.2% vs. 70.2%, RR = 1.29, [95% CI 1.12-1.48]). Moreover, compared with the hysteroscopic niche resection group, the LNG-IUS group had significantly fewer postmenstrual spotting days and total bleeding days from six months onwards (all P &amp;lt; 0.001), and less pelvic pain from three months onwards (all P &amp;lt; 0.010). Intervention-related complications were not reported in any of the groups. During follow-up, eleven (10.8%) women reported hormonal related side-effects and two (2.0%) women had spontaneous partial expulsion in the LNG-IUS group, while in the hysteroscopic niche resection group three unintended pregnancies were reported. Limitations, reasons for caution Due to the nature of the intervention, it was not possible to blind participants and gynaecologists for treatment allocation.The cut-off value chosen for our primary outcome and the moment of assessment for our primary endpoint can both be debated. Wider implications of the findings LNG-IUS provides an alternative treatment for women with niche-related gynaecological symptoms and no active desire to become pregnant. Trial registration number Chinese Clinical Research Center (ChiCTR1900025677)

Effects of high-intensity focused ultrasound combined with levonorgestrel-releasing intrauterine system on patients with adenomyosis

It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50–400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60–100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P < 0.05) decreased from 31.4 ± 3.5 days before treatment to 28.6 ± 1.9 days, the menstrual period was significantly shortened from 7.9 ± 1.2 days before HIFU to 6.5 ± 1.3 days, and the menstrual volume was significantly (P < 0.05) decreased from 100 to 49% ± 13%. The serum hemoglobin significantly (P < 0.05) increased from 90.8 ± 6.2 g/L before treatment to 121.6 ± 10.8 g/L at six months for patients with anemia. Among seventy-two (92.3%) patients who finished the six-month follow-up, sixty-five (90.3%) patients had the dysmenorrhea completely relieved, and the other seven (9.7%) patients had only slight dysmenorrhea which did not affect their daily life. Adverse events occurred in 24 (18.3%) patients without causing severe consequences, including skin burns in two (1.5%) patients, skin swelling in four (3.1%), mild lower abdominal pain and low fever in 15 (11.5%), and subcutaneous induration in three (2.3%). Six months after treatment, no other serious side effects occurred in any patients with follow-up. In conclusions, the use of high-intensity focused ultrasound combined with the levonorgestrel-releasing intrauterine system for the treatment of adenomyosis is safe and effective even though the long-term effect remains to be confirmed.

COMPARISON OF SAFETY AND EFFICACY OF ORAL PROGESTERONE WITH LEVONORGESTREL INTRAUTERINE SYSTEM IN MANAGEMENT OF DYSFUNCTIONAL UTERINE BLEEDING

The retrospective study was conducted in the Department of Obstetrics and Gynaecology, Nishtar Medical Hospital, Multan, to compare the safety and efficacy of oral progesterone and levonorgestrel-releasing intrauterine system (LNG-IUS) for the management of DUB. The study was conducted on 90 patients who fulfilled the inclusion criteria. Participants were randomly divided into groups A (LNG-IUS) and B (oral progesterone). The primary outcomes were Pictorial blood loss assessment chart (PBAC) scores. Secondary outcomes were the evaluation of adverse effects and Hb levels. A comparison of the mean PBAC score showed that LNG-IUS significantly reduced PBAC scores (P&lt; 0.0001). Comparison of post-treatment HB levels showed that LNG-IUS significantly increased Hb level, and the difference between both groups was statistically significant (P&lt; 0.0001). After 6 months, the incidence of adverse effects in group B was 60%, while in group A was 40%. However, hypomenorrhea was more prevalent in group A. It can be concluded that LNG-IUS is a more effective and safe treatment choice for Dub compared to oral progesterone.

Perimenopausal abnormal uterine bleeding

Abnormal uterine bleeding is a very frequent symptom in the perimenopause. The causes are numerous ranging from physiological reactions due to decreasing/instable ovarian function to premalignant and malignant conditions. Benign findings such as endometrial polyps and myomas are increasing with age, leading to more abnormal uterine bleeding in the perimenopause. Cervical and vaginal causes of abnormal uterine bleeding should also be excluded by speculum examination. Sexually transmitted diseases should be ruled out in the perimenopausal women in new relationships. Measurement of hemoglobine, human chorion gonadotropine and thyreoid hormones are relevant in selected cases. Transvaginal ultrasound is the primary diagnostic tool in perimenopausal abnormal uterine bleeding. Saline or gel contrast sonohysterography improves the diagnostic accuracy. Based on the findings by ultrasound, more invasive procedures such as blind endometrial biopsy or hysteroscopy can be planned. Once premalignant and malignant causes are excluded, the necessity for treatment can be evaluated in collaboration with the individual woman. Severe heavy menstrual bleeding causing anaemia will need immediate treatment. In less severe cases and in intermenstrual bleeding expectant management can be considered. Hormonal medical treatment e.g., progestins or insertion of levonorgestrel-releasing intrauterine system (LNG-IUS) is a possibility in case of anovulatory bleeding interfering with the quality of life. The amount of bleeding can be reduced both by antifibrinolytic and non-steroidal anti-inflammatory drugs and LNG-IUS. In case of focal intrauterine lesions, such as endometrial polyps or submucous myomas, operative hysteroscopic procedures are warranted in the treatment of abnormal uterine bleeding. Other minimally invasive procedures, such as endometrial ablation or endometrial resection, is a good choice in selected cases, but some women will need a hysterectomy as a definite treatment of abnormal uterine bleeding in perimenopause.

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

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. 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 5mg 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. 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. 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. UK Medical Research Council and National Institute of Health Research EME Programme (12/206/52).

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.

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.

Immediate Postpartum Long-Acting Reversible Contraception Uptake and Outcomes [ID: 1371558

INTRODUCTION: Tennessee Medicaid began covering immediate postpartum (IPP) long-acting reversible contraception (LARC) in November 2017 with the goal of reducing the rate of short-interval births (SIBs) (defined as less than 24 months after a previous birth). In 2014, 22.7% of births in Tennessee were SIBs. We sought to determine IPP LARC uptake and SIB outcomes for women who received IPP LARC after this policy was implemented. METHODS: A retrospective chart review of women who delivered from March to December 2018 and received IPP LARC was conducted. LARC receipt and SIB outcomes were determined utilizing local, regional, and state records (IRB: 4768, 2021-0303). RESULTS: Among the 406 IPP LARC recipients, the average age was 25.9 (15–42), and the average number of living children was 1.28 (0–6). LARC type elected was 4.7% copper intrauterine system (Cu-IUS), 39.9% levonorgestrel-releasing intrauterine system (LNG-IUS), and 55.4% contraceptive implant. Subsequent SIB was identified in only 5.4% (22). Of these, 2 received Cu-IUS, 10 received LNG-IUS, and 10 received contraceptive arm implants. Timing and reason for removal were documented for 7 of these. Expulsion was identified in 1 copper and 1 hormonal IUD. Removals due to side effects were reported in 3 implant and 2 hormonal IUD users. CONCLUSION: The rate of SIB among the IPP LARC recipients was much lower than the general rate among Tennessee women, highlighting the benefit of IPP LARC provision. Additionally, the high preference for contraceptive implants may reflect provider counseling on the increased risk of IUD expulsion when placed IPP or other factors that may be elucidated by future studies.

Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

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.

Abstract 5769: Disparities in uptake of levonorgestrel-releasing intrauterine system (LNG-IUS): implications for uterine cancer primary prevention

Abstract Introduction: Levonorgestrel-releasing intrauterine system (LNG-IUS) is associated with ~50% risk reduction for uterine cancer incidence and can be an effective primary prevention strategy. We aimed to understand current patterns of LNG-IUS use and identify disparities that could inform implementation strategies for more effective and equitable uterine cancer primary prevention. Methods: We analyzed LNG-IUS use among U.S. women aged 18-50 with the 2017-2019 National Survey of Family Growth. Statistical analysis was stratified by race, sociodemographic, and health factors. Predictors of LNG-IUS use were assessed through weighted multivariable logistic regression using the Wald chi-square test. Results: Current LNG-IUS use was significantly lower in Hispanic women compared to White women (AOR 0.65, P=0.049). Compared to women with up to a high school education, LNG-IUS use was higher for women with a college degree or higher in the overall sample (AOR 1.86, P=0.009), White women (AOR 1.91, P=0.04), and Black women (AOR 4.54, P=0.007), but not for Hispanic women (AOR 0.79, P=0.64). All racial/ethnic subgroups had lower odds of LNG-IUS for non-parous women than parous women (all P&amp;lt;0.002). Although a known uterine cancer risk factor, obesity was not associated with LNG-IUS use. Conclusions: Hispanic women, women with lower educational levels, and nulliparous women have disproportionately low LNG-IUS use despite being at increased uterine cancer risk. Community-based educational interventions for high-risk women and their providers on the benefits of LNG-IUS on uterine cancer prevention are needed to mitigate uterine cancer disparities. Table 1. Logistic Regression on Predictors for LNG-IUS Use in U.S. Women Aged 18-50 OVERALL (N=4107) WHITE (n=1948) HISPANIC (n=1052) BLACK (n=861) AOR (95% CI) AOR (95% CI) AOR (95% CI) AOR (95% CI) Race Ref 0.65* (0.42-0.98) 0.77 (0.46-1.27) Age 18-24 1.16 (0.55-2.46) 1.15 (0.45-2.94) 13.13* (1.42-121.3) 0.55 (0.11-2.83) 25-34 1.65 (0.88-3.10) 1.46 (0.69-3.13) 31.75** (4.04-249.5) 0.63 (0.18-2.14) 35-44 1.07 (0.55-2.10) 1.10 (0.49-2.47) 13.28* (1.51-116.6) 0.54 (0.14-2.02) 45-50 Ref Ref Ref Ref Education ≤High School Ref Ref Ref Ref Some College 1.56* (1.02-2.51) 1.56 (0.83-2.94) 1.05 (0.47-2.32) 3.90* (1.39-10.96) ≥Bachelor’s 1.86** (1.17-2.97) 1.91* (1.03-3.54) 0.79 (0.30-2.12) 4.54** (1.51-13.65) BMI Normal Ref Ref Ref Ref Overweight 1.44 (0.93-3.22) 1.40 (0.81-2.41) 0.96 (0.35-2.62) 1.54 (0.56-4.22) Obese 0.87 (0.57-1.31) 0.86 (0.52-1.43) 0.68 (0.28-1.63) 1.01 (0.35-2.89) Parity Parous 2.85*** (1.89-4.30) 2.21** (1.33-3.67) 7.30*** (2.61-20.38) 5.38*** (2.27-12.76) Nulliparous Ref Ref Ref Ref Abbreviations: AOR, adjusted odds ratio; BMI, body mass index; CI, confidence interval; Ref, reference group. *P&amp;lt;0.05; ** P&amp;lt;0.01; *** P&amp;lt;0.001 aEarly Menarche &amp;lt;12yo; Normal Menarche 12-14yo; Late Menarche &amp;gt;14yo. Citation Format: Paul G. Yeh, Iakovos Toumazis, Charlotte Sun, Karen Lu, Larissa A. Meyer. Disparities in uptake of levonorgestrel-releasing intrauterine system (LNG-IUS): implications for uterine cancer primary prevention. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5769.