Treatment Of Heavy Menstrual Bleeding Research Articles

Retrospective study on the outcomes and satisfaction with endometrial ablation by bipolar energy (NovaSure®) for the treatment of heavy menstrual bleeding.

To determine the effectiveness, safety, and participant satisfaction with endometrial ablation by bipolar energy (NovaSure®) in the treatment of heavy menstrual bleeding (HMB), and to investigate factors associated with poorer outcomes. Multicenter retrospective observational study based on medical record review of the outcomes related to endometrial ablation by the bipolar-energy technique procedure to treat HMB in the setting of three university teaching hospitals in Spain. A total of 333 women were included in the study. Most bipolar-energy ablations were successful (85.12%; n = 269 out of 316), with amenorrhea the most frequent outcome (39.6%, n = 131 out of 316). The majority of participants had no complications (95.5%; n = 317 out of 332), and of those who did, only 2.1% were related to the technique. No further treatment was required for HMB in 82.8% of women (n = 274 out of 331), and surgery was avoided in 91.8%; only 5.9% of women underwent ablation-related hysterectomy. In women with previous transverse cesarean sections (CS), 91.0% avoided subsequent surgical treatment. Eighty-six percent of women (n = 221 out of 257) were satisfied with the procedure. Bipolar-energy ablation is very effective and safe for the treatment of HMB and yielded a high rate of participant satisfaction in our setting. The presence of comorbidities or previous CSmay slightly reduce the effectiveness of the method, while performing concomitant surgery (mainly curettage) increases the rate of complications. Notably, despite the known increased risk of hysterectomy, most participants with previous CSs who underwent ablation avoided major surgery.

Patients’ motives and considerations on treatment decision-making for heavy menstrual bleeding: a qualitative study

BackgroundSeveral treatment modalities for heavy menstrual bleeding are available. However, many women report being unsatisfied in their search for an appropriate and effective treatment. The aim of this study is to gain insights in the experienced impact of heavy menstrual bleeding and the motives and considerations of women during the decision-making process for treating heavy menstrual bleeding.MethodsAn interpretative qualitative study was performed, using in-depth interviews. In total, 14 semi-structured interviews were conducted with patients who consulted a physician for treatment of heavy menstrual bleeding. Participants were recruited via the Netherlands Patients Federation (N = 10) or via the outpatient clinic in the Máxima Medical Center (N = 4). The interviews were conducted by phone or online between February 2020 and March 2021. In the interviews three topics were addressed: (1) participant’s experience with heavy menstrual bleeding, (2) experience with patient journey of treatment decision-making and (3) elaborating on alternative treatments for heavy menstrual bleeding. A thematic analysis was conducted.ResultsFourteen participants aged between 30 and 59 years old were interviewed. Three main themes emerged; “Considerations in taking the (next) step to seek help”, “Various sources of information can contribute, confuse or frighten decision-making process” and “A physician’s understanding and a relationship of trust are needed to guide the decision-making process”.ConclusionOur results show that women’s considerations and decision making strongly depend on the obtained information and experience, the relationship with the physician, the influence of the social environment, the pre-visit expectations/desires, the fear of treatment complications and uncertainty of the effect of the treatment. It is a physicians role to create a trusting and open atmosphere during consultation. Patient-centered communication is helpful to share knowledge, and gain insights into a patient’s hopes, fears and worries.

P-321 Uterine fibroids secrete vasodilatory factors that induce their response via the opioid pathway

Abstract Study question Do uterine fibroids produce vasoactive factors that could affect vasculature and induce fibroid associated symptoms? Summary answer Ex vivo secretions from uterine fibroids induce a vasodilatory response in rat mesenteric arteries that is mediated via the opioid receptor pathway. What is known already Uterine fibroids (leiomyoma) are a common but clinically neglected gynaecological condition, where benign smooth muscle tumours arise from the myometrium and cause heavy menstrual bleeding (HMB), pain and infertility. Fibroids affect up to one in two women of reproductive age and are the main reason for failure of both medical and surgical treatments in women with HMB. Fibroids are proposed to affect the systemic vasculature system, with angiogenic growth factors and abnormal vasculature implicated in fibroid pathophysiology. However, the precise mechanism of fibroid induced HMB has yet to be fully elucidated. Study design, size, duration Fibroid and myometrium biopsies were prospectively collected from 13 patients undergoing MyoSure, myomectomy or hysterectomy for the treatment of HMB associated with fibroids at Liverpool Women’s Hospital, a tertiary referral centre. The collection and use of human tissue was ethically approved, and all participants gave informed written consent. Tissue biopsies were incubated in a basal medium for 24 hours. Conditioned medium was collected and used for wire myography assays to examine vascular reactivity. Participants/materials, setting, methods Second order mesenteric arteries from female Wistar rats were mounted on a wire myograph system and toned with uridine triphosphate (UTP) before being exposed to control (non-conditioned), normal myometrium (n = 4) or fibroid (n = 9) conditioned medium. Vascular activity was measured relative to UTP induced vasoconstriction. To determine the mediatory factors of observed vasoreactivity, inhibitors of well characterised pathways were systematically tested in the presence of conditioned medium. Main results and the role of chance Fibroid conditioned medium caused a marked dilation of UTP induced vasoconstriction in rat mesenteric arteries, which was significantly greater than that induced by non-conditioned, or control myometrium conditioned medium. Blockage of ATP-sensitive potassium (KATP) channels with PNU37883A completely inhibited fibroid induced vasodilation. However, blockage of other potassium channels did not inhibit dilation, suggesting that a KATP-mediated PKA-dependent pathway is being stimulated. To test the potential involvement of endothelial-derived nitric oxide synthase in vasodilation, vessels were treated with the inhibitor L-NAME, which partially blocked fibroid induced vasodilation. The specificity of nitric oxide synthase inhibition was confirmed by treating vessels with acetylcholine or carbachol, which induced vasodilation via activation of nitric oxide synthase. In the presence of L-NAME, the vasodilatory effects of acetylcholine and carbachol were blocked, thus confirming inhibitor specificity. An adenosine receptor inhibitor, theophylline, had no effect on fibroid induced vasodilation, thus ruling out the adenosine pathway. Blockage of bradykinin and adrenergic receptors also failed to prevent fibroid induced dilation in mesenteric arteries. However, blocking opioid receptors with naloxone completely inhibited vasodilation in the presence of fibroid conditioned medium. These findings suggest that fibroid induced vasodilation is mediated via endothelial nitric oxide synthase and an unknown opioid compound. Limitations, reasons for caution This study was performed using excised tissue in an ex vivo environment, which may not fully simulate the fibroid secretome in vivo. Although rat mesenteric arteries are a well-established model, human uterine arteries may be more appropriate to study fibroid induced vasoreactivity. Wider implications of the findings Fibroids are responsible for up to half of all hysterectomies and healthcare costs run into the billions globally. This study demonstrates that fibroid secreted factors can impact vasoreactivity, which has important connotations for disease pathophysiology regarding HMB. Targeting vasoactive compounds produced by fibroids may be a future novel treatment option. Trial registration number NA

A plain language summary of the perspectives of women who were interviewed about their experiences with uterine fibroids.

This summary describes what researchers learned during interviews of women with uterine fibroids and heavy menstrual bleeding (or period bleeding). At this time, little is known about how women perceive the impact of uterine fibroids on their lives and more information is needed. The goal of this study was to provide new information about the symptoms women have and how these symptoms affect their everyday lives. These interviews were done to better understand how uterine fibroid symptoms affect the lives of women in their own words. Thirty women from the United States, who had completed a clinical trial for a new treatment for heavy menstrual bleeding and uterine fibroids, agreed to be interviewed. The women described what their experiences with uterine fibroids were and the impact these experiences with uterine fibroids had on their lives before participating in the clinical trial. The most common symptoms of uterine fibroids the women described were heavy bleeding with their menstrual periods, pain in the pelvis or groin area, the passing of blood clots, and anemia (or low hemoglobin in red blood cells). Women said their symptoms affected them physically, emotionally, socially, and financially. They also said their symptoms made it hard to do daily activities, sleep, have a sex life, and go to work or school. Women who have heavy menstrual bleeding and uterine fibroids experience various uterine fibroid symptoms, and these symptoms affect most parts of the their lives.

Heavy menstrual bleeding in adolescence: who to investigate and how to manage it

Key content Adolescent heavy menstrual bleeding (HMB) is commonly related to hypothalamic pituitary ovarian axis immaturity, which improves with age. This article outlines when and how to investigate for underlying pathological causes. Medical treatment for adolescent HMB consists predominantly of hormonal contraceptives. Preparation choice depends upon patient preference, comorbidities and co‐existing conditions. Acute adolescent HMB is rare; a suggested framework for assessing and managing such cases is provided within this article. Learning objectives To understand how to clinically evaluate adolescent HMB. To understand when and how to investigate adolescent HMB. To understand the different medical treatment options for HMB, their efficacy, risks and alternatives. To understand the management of acute adolescent HMB. Ethical issues Duties of confidentiality must be balanced against safeguarding concerns.

A Comprehensive Approach: Correlating Ultrasound Imaging with Endometrial Histopathological Analysis in Perimenopausal Women with Heavy MenstrualBleeding.

Abnormal uterine bleeding (AUB) is a common troublesome symptom in the perimenopausal age group. The most common type of AUB in this age group is heavy menstrual bleeding. There is a risk of endometrial carcinoma and atypical endometrial hyperplasia in women with AUB in the age group of 40-50 years. Hence early evaluation is of paramount importance in managing women with perimenopausal heavy menstrual bleeding. The current study was undertaken to study the correlation between ultrasound findings and various benign and malignant endometrial histologies in perimenopausal women with heavy menstrual bleeding. Women aged 40-55 years presenting with heavy menstrual bleeding at the gynaecology outpatient department at Sree Balaji Medical College and Hospital, Chennai, India, were included in the study. Patients on anti-platelet and anti-coagulation therapy and patients already on hormonal treatment for heavy menstrual bleeding were excluded from the study. The demographic factors, symptom profiles, ultrasound findings, and histopathological reports were tabulated and analysed. Of the 147 women included in the study, 75 (51%) were aged 45-50 years and 107 (73%) had two or more pregnancies. Fibroid was the common non-endometrial cause of heavy menstrual bleeding in 52 (35%) cases. The proliferative pattern was the most common non-pathological histology identified in 46 (31%) cases. Endometrial hyperplasia without atypia was the most common pathological histology observed in the study population. Endometrial thickness of more than 8 mm was strongly associated with premalignant or malignant endometrial lesions. Our study has attempted to identify the correlation between ultrasound evaluation of perimenopausal women with heavy menstrual bleeding and endometrial pathology. Ultrasound, being cost-effective and widely available, is proven to be a tool for first-line investigation of perimenopausal women with heavy menstrual bleeding that guides further evaluation and management.

Hysteroscopic Partial Endometrial Resection Versus Thermal Balloon Ablation for Treatment of Heavy Menstrual Bleeding in Premenopausal Women

Hysteroscopic Partial Endometrial Resection Versus Thermal Balloon Ablation for Treatment of Heavy Menstrual Bleeding in Premenopausal Women

Meclizine improves endometrial repair and reduces simulated menstrual bleeding in mice with induced adenomyosis

BackgroundAdenomyosis is one of the structural causes of abnormal uterine bleeding, which often presents as heavy menstrual bleeding (HMB). Mostly due to poor understanding of its pathophysiology, medical management of adenomyosis-induced HMB is still a challenge. We have previously reported that glycolysis is crucial to endometrial repair following menstruation and that suppressed glycolysis can cause HMB. Objective(s)To test the hypothesis that meclizine, a drug with excellent safety profile, alleviates HMB in mice with induced adenomyosis using a simulated menstruation model. Study DesignAdenomyosis was induced in 36 female C57BL/6 mice using endometrial-myometrial interface disruption. Three months after induction, the mice were randomly divided into three groups: low- and high-dose meclizine, and controls. Treatment with meclizine or vehicle started shortly before the simulated menstruation procedure and ended before progesterone withdrawal. The amount of blood loss was quantitated and uterine tissue was harvested for histological evaluation of the grade of endometrial repair. We performed immunohistochemistry analysis of 4 proteins critically involved in glycolysis, namely glucose transporter 1 (Glut1), hexokinase 2 (Hk2), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) and pyruvate kinase 2 (Pkm2). The extent of tissue fibrosis in both ectopic and eutopic endometrium was evaluated using Masson trichrome staining. ResultsIn mice with induced adenomyosis, meclizine accelerated endometrial repair in a dose-dependent manner and reduced the amount of menstrual bleeding. Meclizine administration raised endometrial immunoexpression of Hk2 and Pfkfb3 but not of Glut1 or Pkm2.The extent of endometrial fibrosis was reduced following the meclizine administration. Remarkably, these favorable changes were accompanied with suppression of lesional progression, as evidenced by the dose-dependent reduction in the extent of fibrosis (a surrogate for lesional progression). Conclusion(s)These encouraging results, taken together, suggest that glycolysis may be a promising therapeutic target and that meclizine may hold a therapeutic potential as a non-hormonal treatment for adenomyosis-induced HMB without exacerbating the disease.

The efficacy of medical management of leiomyoma-associated heavy menstrual bleeding: a mini review

Leiomyomas, or fibroids, are benign uterine tumors that are commonly associated with abnormal uterine bleeding-L particularly heavy menstrual bleeding (HMB). Treatment options include expectant, medical, image-guided, and surgical. Medical management of HMB is the preferred first-line treatment and includes nonsteroidal anti-inflammatory drugs, contraceptive hormones, tranexamic acid, levonorgestrel intrauterine system, gonadotropin-releasing hormone (GnRH) antagonists and antagonists, selective progesterone receptor modulators, selective estrogen receptor modulators, and aromatase inhibitors. Although alternatives such as vitamins and supplements have been suggested, there is currently a lack of robust evidence of their efficacy. Many of these therapies treat the symptoms rather than the underlying pathology. Progestin-based therapies are the most commonly utilized, although research supporting their effectiveness in the treatment of HMB is modest. Although GnRH agonists and antagonists, which are federal drug administration-approved therapies, provide substantial improvement in abnormal uterine bleeding-L with HMB, the effects typically last for the duration of therapy. Patients may also face financial barriers to GnRH analog therapy. Future studies are required to delineate the nonhormonal treatment options and the long-term management of leiomyoma-associated HMB.

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.

Low-Dose Elagolix for the Treatment of Heavy Menstrual Bleeding in Patients With Uterine Leiomyomas: A Randomized Controlled Trial.

To evaluate the safety and efficacy of elagolix 150 mg once-daily monotherapy in patients with heavy menstrual bleeding associated with uterine leiomyomas. A phase 4, randomized, double-blind, placebo-controlled, 6-month treatment study was conducted in premenopausal patients aged 18-51 years with heavy menstrual bleeding (defined as menstrual blood loss greater than 80 mL during one menstrual cycle) associated with uterine leiomyomas. Patients were randomized 2:1 to receive elagolix 150 mg once daily or placebo. The primary endpoint was reduction in menstrual blood loss volume to less than 80 mL at the final month and at least a 50% reduction in menstrual blood loss volume from baseline to the final month. Of 82 randomized patients, 54 received elagolix 150 mg and 28 received placebo. With elagolix, 49.4% (95% CI 35.1-63.8%) of patients met the primary endpoint, compared with 23.3% (95% CI 7.2-39.5%) of patients who received placebo ( P =.035). Statistically significant differences between elagolix and placebo in mean reduction of menstrual blood loss from baseline were seen as early as month 1 ( P <.05 for months 1-3 and 5). Significantly more patients receiving elagolix experienced suppression of bleeding compared with placebo ( P =.036). Greater improvements were observed in the elagolix group (vs placebo) in the proportion of patients with amenorrhea, in hemoglobin concentrations, and in health-related quality of life. No serious or severe adverse events were reported for elagolix, compared with 7.1% of participants in the placebo group having serious adverse events (coronavirus disease 2019 [COVID-19] n=1, enlarged uvula n=1). Three patients (5.6%) discontinued elagolix due to adverse events. Elagolix 150 mg once-daily monotherapy significantly improved heavy menstrual bleeding associated with uterine leiomyomas compared with placebo in premenopausal patients. Treatment with elagolix 150 mg once daily was generally well-tolerated in this study, with no new safety signals. AbbVie Inc. ClinicalTrials.gov , NCT03886220.

Primary Hemostasis Disorders as a Cause of Heavy Menstrual Bleeding in Women of Reproductive Age.

Heavy menstrual bleeding (HMB) is a common clinical condition affecting adolescent and adult women and compromising their quality of life. Primary hemostasis disorders, affecting platelet plug formation, can be the underlying cause of HMB. They comprise a heterogeneous group of diseases with Von Willebrand disease (VWD) being the most commonly diagnosed; other disorders in this group that have been linked to HMB include (a) Glanzmann thrombasthenia, (b) Bernard-Soulier syndrome, (c) Hermansky-Pudlak syndrome, (d) immune thrombocytopenia (ITP), and (e) Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Diagnosing these diseases can be challenging, as the basic laboratory investigations can be within the normal range. Thus, identification of specific clinical features and a thorough hematologic workup can be very important, providing the correct diagnosis. Proper diagnosis of the underlying disorder is important, as management may vary accordingly. Although disease-specific management guidelines exist for some of these disorders such as VWD and ITP, due to the rarity of most primary hemostasis disorders, the best approach for the management of HMB in these women remains elusive. The goal of this study was to create an informative, comprehensive review of the primary hemostasis disorders that have been linked to HMB. This study provides a summary of the basic published information regarding epidemiology, pathophysiology, clinical phenotype, diagnosis, and treatment of HMB in those diseases and serves as a reference guide for further reading.

A randomized trial comparing the 52-mg levonorgestrel system with combination oral contraceptives for treatment of heavy menstrual bleeding

The levonorgestrel intrauterine system and combined oral contraceptives are the 2 most commonly used nonsurgical treatments for heavy menstrual bleeding in the United States. However, there are limited data on their relative effectiveness and on their impact on bleeding-specific quality of life. This study aimed to compare the effectiveness of the 52-mg levonorgestrel intrauterine system with that of combined oral contraceptives for improving quality of life among individuals who self-report heavy menstrual bleeding. We hypothesized that the levonorgestrel intrauterine system would be more effective than combined oral contraceptives at 6 and 12 months after treatment. We conducted a pragmatic randomized trial of individuals who self-reported heavy menstrual bleeding. Individuals were eligible if they did not have contraindications to either the levonorgestrel intrauterine system or combined oral contraceptives and were determined to have a nonstructural cause of heavy menstrual bleeding. Eligible and consenting participants were randomly assigned in a 1:1 ratio to receive a 52-mg levonorgestrel intrauterine system or a monophasic 30- or 35-μg ethinyl estradiol-containing combined oral contraceptive. The main outcome was mean change in bleeding-related quality of life, measured by the 20-question Menstrual Bleeding Questionnaire (score range, 0-75) at 6 and 12 months. Differences in group means and confidence intervals for the Menstrual Bleeding Questionnaire score were computed by multivariable linear mixed-effects regression; 24 participants per group were needed to detect a 10-point difference in change in mean Menstrual Bleeding Questionnaire score between individuals treated with the levonorgestrel intrauterine system and those treated with combined oral contraceptives at each follow-up time point. A total of 62 individuals were randomly assigned to treatment (n=29 allocated to levonorgestrel intrauterine system and n=33 allocated to combined oral contraceptives) and included in the intention-to-treat analyses; 19 of 29 received the levonorgestrel intrauterine system and 31 of 33 received combined oral contraceptives. Eleven percent identified as Black or African American and 44% identified as Hispanic or Latina. Participant characteristics were similar among study groups. Bleeding-related quality of life increased in both study arms, as reflected by a significant decrease in Menstrual Bleeding Questionnaire scores beginning at 6-week follow-up. In the main intention-to-treat analyses (n=62), there were no differences in mean change in Menstrual Bleeding Questionnaire scores at 6 months (difference=-2.5; 95% confidence interval,-10.0 to+5.0) or 12 months (difference=-1.1; 95% confidence interval,-8.7 to+6.5). Findings were similar in the subsets of participants with any follow-up visits (n=52) and who completed all follow-up visits (n=42). In the per-protocol analyses (n=47), a significantly greater decrease in Menstrual Bleeding Questionnaire score was observed in the levonorgestrel intrauterine system arm at 6 months after treatment (difference=-7.0; 95% confidence interval,-13.8 to-0.2) but not at 12 months (difference=-4.8; 95% confidence interval,-11.8 to 2.3) compared with the combined oral contraceptive arm. No differences in change of bleeding-related quality of life were observed between the levonorgestrel intrauterine system and combined oral contraceptives at 6 or 12 months. Patients should be counseled that the levonorgestrel intrauterine system and combined oral contraceptives are both effective options for improving bleeding-related quality of life.

Efficacy and safety of vilaprisan in women with uterine fibroids: data from the ASTEROID 3 randomized controlled trial

Vilaprisan is a highly potent selective progesterone receptor modulator shown to reduce heavy menstrual bleeding, induce amenorrhea, and diminish uterine fibroid volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids. Randomized, double-blind, placebo-controlled, multicenter phase 3 study. Hospitals and medical centers. Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle. Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed. Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study. Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies. Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted. NCT03400943 (ClinicalTrials.gov).

Endometrium Ablation using a Foley catheter with a cost-effective technique in a hospital environment.

Objective: To evaluate the effectiveness of employing Foley’s catheter and modified thermal balloon ablation to treat heavy menstrual bleeding (HMB). Study Design: Prospective Interventional Randomized Control study. Setting: Departments of Gynecological of Three Semi Government Hospitals of the City. Period: January 2021 to September 2022. Material &amp; Methods: In the study, 12 patients between the ages of 42 and 50 who complained of menorrhagia and who had not responded to treatment for at least 6 months were recruited. Pre-ablation endometrial curettage was performed on each patient. A 30-50 ml latex covered Foley’s Catheter was evaluated after being introduced into uterine cavity, inflated as much as the cavity would allow under moderate pressure, and changed every two minutes with fresh boiling saline for eight minutes. Following that, hysteroscopic examination and a 6-month follow-up were performed to look for endometrial scarring. Results: Significantly shorter hospital stays, shorter recovery times following surgery, and quicker return to normal daily and sexual activities. Regarding problems, menstrual alterations, amenorrhea rate, and failure rate during the course of follow-up, there was no discernible difference between patients. This method has a success rate of almost 88%. Conclusion: In situations with limited resources, improved thermal balloon ablation with a Foley’s catheter can be a potential treatment for HMB. It is a more affordable option that the preliminary endometrial ablation approaches.

Qualitative study exploring which research outcomes best reflect women’s experiences of heavy menstrual bleeding: stakeholder involvement in development of a core outcome set

ObjectiveThis work contributed to the development of a core outcome set (COS) for heavy menstrual bleeding (HMB). The objective was to determine which research outcomes best reflect how HMB affects...

Endometrial ablation and resection versus hysterectomy for heavy menstrual bleeding: an updated systematic review and meta-analysis of effectiveness and complications.

To evaluate the clinical efficacy, safety, and cost-effectiveness of endometrial ablation or resection (E:A/R) compared to hysterectomy for the treatment of heavy menstrual bleeding (HMB). Literature-search was performed for all the randomized control trials (RCTs) comparing (E:A/R) versus hysterectomy for the treatment of HMB. The literature-search was last updated in November 2022. The primary outcomes were objective and subjective reduction in HMB and patient-satisfaction rates in improving the bleeding symptoms at 1-14 years. The data were analyzed using Review Manager software. Twelve RCTs with 2,028 women (hysterectomy: n=977 vs. E:A/R: n=1,051) were included. Hysterectomy was compared with endometrial ablation in 5 studies, endometrial resection in 5 studies, and both ablation and resection in 2 studies. The meta-analysis revealed that the hysterectomy group showed improved patient-reported and objective bleeding-symptoms more than those of the EA/R group with risk ratios (RR) of (MD, 0.75; 95% CI, 0.71 to 0.79) and (MD, 44.00; 95% CI, 36.09 to 51.91), respectively. The patient-satisfaction was higher post-hysterectomy up to a follow-up period of 2 years (RR, 0.90; 95% CI, 0.86 to 0.94) but this effect was absent with long term follow-up. This meta-analysis shows that E:A/R offers alternatives to hysterectomy. Although both procedures are highly effective, safe, and improve the quality of life, hysterectomy is significantly superior at improving the bleeding symptoms and patient satisfaction up to two-years. However, hysterectomy is associated with longer operating times and recovery periods and has a higher rate of postoperative complications. The initial cost of E:A/R is less than that of hysterectomy but further surgical requirements are common, therefore there is no difference in the cost for the long term follow-up.

Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB).

Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)? Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids. SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids. In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology. A cohort of 19 women aged 38-52years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI). Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (P = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (P = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (P = 0.17). The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected. The imaging protocol that we have developed represents a generic paradigm for measuring the volume of the uterus and uterine fibroids that can be readily incorporated in future studies of medical treatments of HMB. In the present study, SPRM-UPA failed to produce a significant reduction in the volume of the uterus or the total volume of fibroids (which were present in approximately half of the patients) after either two or three 12-week courses of treatment. This finding represents a new insight in respect of the management of HMB using treatment strategies that target hormone-dependence. The UPA Versus Conventional Management of HMB (UCON) trial was funded by the EME Programme (Medical Research Council (MRC) and National Institutes of Health Research (NIHR)) (12/206/52). The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care.Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. H.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (All paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., and Myovant Sciences GmbH. H.C. has received royalties from UpToDate for an article on abnormal uterine bleeding. L.W. has received grant funding from Roche Diagnostics (Paid to Institution). All other authors have no conflicts to declare. The study reported here is an embedded mechanism of action study (no comparator) within the UCON clinical trial (registration ISRCTN: 20426843).

Standardising outcome reporting for clinical trials of interventions for heavy menstrual bleeding: Development of a core outcome set.

To develop a core outcome set for heavy menstrual bleeding (HMB). Core outcome set (COS) development methodology described by the COMET initiative. University hospital gynaecology department, online international survey and web-based international consensus meetings. An international collaboration of stakeholders (clinicians, patients, academics, guideline developers) from 20 countries and 6 continents. Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two-round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS. Outcome importance was assessed in the Delphi survey on a 9-point scale. From the 'long list' of 114, 10 outcomes were included in the final COS: subjective blood loss; flooding; menstrual cycle metrics; severity of dysmenorrhoea; number of days with dysmenorrhoea; quality of life; adverse events; patient satisfaction; number of patients going on to have further treatment for HMB and haemoglobin level. The final COS includes variables that are feasible for use in clinical trials in all resource settings and apply to all known underlying causes of the symptom of HMB. These outcomes should be reported in all future trials of interventions, their systematic reviews, and clinical guidelines to underpin policy.