Changes In Menstrual Blood Loss Research Articles

Comparison of efficacy between levonorgestrel intrauterine system and dienogest in adenomyosis: a randomized clinical trial.

Medical management of adenomyosis is an emerging perspective in modern gynecology. Though levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG) effectively relieve symptoms in adenomyosis, neither has been approved for the same indication. Our study aims to compare the efficacy and safety of these progestins in treating adenomyosis. To study the efficacy and safety of LNG-IUS versus DNG in patients with symptomatic adenomyosis. Open-labeled, parallel, single-centered, randomized clinical trial. Patients with adenomyosis-associated pain with or without abnormal uterine bleeding were randomly allocated to either LNG-IUS group or DNG group. The primary outcome was a reduction in painful symptoms after 12 weeks of treatment measured by visual analog scale (VAS) score. Changes in menstrual blood loss (MBL), improvement in quality of life (QoL), and adverse drug reactions were also analyzed. The VAS score significantly decreased from baseline in both groups. The baseline and post-treatment VAS scores in the LNG-IUS group were 6.41 ± 1.07 and 3.41 ± 1.04 (p = <0.001) and in the DNG group, were 6.41 ± 0.95 and 3.12 ± 1.40 (p = <0.001), respectively. A significantly greater proportion of patients in the LNG-IUS group experienced lighter MBL as compared to the DNG group [27/30 (90%) in the LNG-IUS group versus 17/22 (77.2%) in the DNG group (p = 0.006)]. Both the groups had improvement in QOL scores calculated by the World Heath Organisation QOL scale (WHOQOL BREF) questionnaire; however, it was more pronounced in the DNG group [(28.76 ± 30.47 in the LNG-IUS group versus 48.26 ± 44.91 in the DNG group (p = 0.04)]. Both the agents were safe as there were no reported major adverse drug reactions. DNG can be an effective and safe alternative to LNG-IUS for the medical management of adenomyosis. The trial was prospectively registered at the clinical trial registry - India (CTRI) vide CTRI number CTRI/2020/05/025186.

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms

Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment. To determine whether mifepristone is effective and safe for adenomyosis treatment. This multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020. Participants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks. The primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations. In total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was -6.63 (1.92) in the mifepristone group and -0.95 (1.75) in the placebo group (P < .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P < .001), CA125 (mean [SD] change from baseline: -62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P < .001), platelet count (mean [SD] change from baseline: -28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P < .001), and uterine volume (mean [SD] change from baseline: -29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P < .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported. This randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability. ClinicalTrials.gov Identifier: NCT03520439.

POSB139 Predicting Quality of Life through Changes in Menstrual Blood Loss in Patients with Uterine Fibroids

Heavy menstrual bleeding is the main symptom of uterine fibroids (UF), significantly affecting quality of life of women with symptomatic UF, and is measured in most clinical trials involving UF patients. The objective was to develop a predictive utility function based on incremental changes in menstrual blood loss (MBL) to estimate QoL in patients with symptomatic UF for use in health economic models.

Transcervical Fibroid Ablation with the Sonata® System for Treatment of Submucous and Large Uterine Fibroids

Study Objective To examine the role and benefits of transcervical fibroid ablation (TFA) in the treatment of submucous and large uterine fibroids. Design Subgroup analysis of two multicenter, prospective, controlled trials. Setting Academic and community hospitals in the UK, the Netherlands, the US and Mexico. Patients or Participants 197 women who underwent TFA with the Sonata® System within the FAST-EU and SONATA clinical trials. Interventions TFA was used to ablate fibroids under clinical trial protocol. Measurements and Main Results Key outcomes were changes in menstrual blood loss, symptom severity and health-related quality of life on the Uterine Fibroid Symptom and Quality-of-Life Questionnaire, health-related quality of life on the EQ-5D questionnaire, and surgical reinterventions for heavy menstrual bleeding. Among 197 women (with 534 treated fibroids), 86% of women with only submucous fibroids and 81% of women with large fibroids (>5 cm) experienced bleeding reduction within 3 months post-ablation. Overall symptom severity and health-related quality of life showed sustained, significant improvements over 12 months. Additional fibroid mapping of large fibroids with magnetic resonance imaging in the FAST-EU trial showed an average volume reduction of 68%. Among women with only submucous fibroids, the rate of surgical reintervention through 1 year of follow up was 3.7% in FAST-EU and 0.0% in SONATA. Conclusion With the Sonata System, TFA is an effective single-stage treatment option for non-pedunculated submucous myomata, and larger or deeper uterine fibroids (including fibroid clusters) for which hysteroscopic treatment is not suitable. To examine the role and benefits of transcervical fibroid ablation (TFA) in the treatment of submucous and large uterine fibroids. Subgroup analysis of two multicenter, prospective, controlled trials. Academic and community hospitals in the UK, the Netherlands, the US and Mexico. 197 women who underwent TFA with the Sonata® System within the FAST-EU and SONATA clinical trials. TFA was used to ablate fibroids under clinical trial protocol. Key outcomes were changes in menstrual blood loss, symptom severity and health-related quality of life on the Uterine Fibroid Symptom and Quality-of-Life Questionnaire, health-related quality of life on the EQ-5D questionnaire, and surgical reinterventions for heavy menstrual bleeding. Among 197 women (with 534 treated fibroids), 86% of women with only submucous fibroids and 81% of women with large fibroids (>5 cm) experienced bleeding reduction within 3 months post-ablation. Overall symptom severity and health-related quality of life showed sustained, significant improvements over 12 months. Additional fibroid mapping of large fibroids with magnetic resonance imaging in the FAST-EU trial showed an average volume reduction of 68%. Among women with only submucous fibroids, the rate of surgical reintervention through 1 year of follow up was 3.7% in FAST-EU and 0.0% in SONATA. With the Sonata System, TFA is an effective single-stage treatment option for non-pedunculated submucous myomata, and larger or deeper uterine fibroids (including fibroid clusters) for which hysteroscopic treatment is not suitable.

Transcervical fibroid ablation with the Sonata™ system for treatment of submucous and large uterine fibroids.

ObjectiveTo examine the role and benefits of transcervical fibroid ablation (TFA) in the treatment of submucous and large uterine fibroids.MethodsA subgroup of patients with submucous or large fibroids were analyzed from two prospective clinical trials (FAST‐EU and SONATA) of sonography‐guided TFA with the Sonata® system. Key outcomes were changes in menstrual blood loss, symptom severity and health‐related quality of life on the Uterine Fibroid Symptom and Quality‐of‐Life Questionnaire, health‐related quality of life on the EQ‐5D questionnaire, and surgical reinterventions for heavy menstrual bleeding.ResultsAmong 197 women (534 treated fibroids), 86% of women with only submucous fibroids and 81% of women with large fibroids (>5 cm) experienced bleeding reduction within 3 months post‐ablation. Overall symptom severity and health‐related quality of life showed sustained, significant improvements over 12 months. Additional fibroid mapping of large fibroids with magnetic resonance imaging in the FAST‐EU trial showed an average volume reduction of 68%. Among women with only submucous fibroids, the rate of surgical reintervention through 1 year of follow up was 3.7% in FAST‐EU and 0.0% in SONATA.ConclusionWith the Sonata system, TFA is an effective single‐stage treatment option for non‐pedunculated submucous myomata, and larger or deeper uterine fibroids (including fibroid clusters) for which hysteroscopic treatment is not suitable. ClinicalTrials.gov: FAST‐EU, NCT01226290; SONATA, NCT02228174.

Mifepristone Treats Symptomatic Adenomyosis: A Multicentre, Randomized, Double-Blind and Placebo-Controlled Trial

Background: Despite advancements in drug therapy, many patients with adenomyosis fail to achieve treatment goals. Therefore, new therapies need to be developed. Our aim was to evaluate the efficacy, safety and tolerability of mifepristone versus placebo in the treatment of painful adenomyosis. Methods: We conducted a randomized, multicenter, double-blind and placebo-controlled trial in 10 hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio to receive mifepristone or placebo orally once a day for 12 weeks. The randomization sequence was generated by the block-rank package of R software with a block size of four. Randomization was performed centrally with an interactive web response system. Regular trial visits were performed every 4 weeks and lasted to 4 weeks after treatment. Patients, investigators, clinicians and statisticians were masked to the treatment allocation throughout the study. The primary outcome was the change in adenomyosis-associated dysmenorrhea intensity evaluated by visual analog scale (VAS) in intention-to-treat population. Secondary outcomes were the changes in menstrual blood loss, the levels of hemoglobin and CA125, platelet count and uterine volume after 12-week treatment. Safety analyses were done in patients with at least one dose of the product intervention. This trial is registered with ClinicalTrials.gov, NCT03520439. Findings: Between May 2018 and April 2019, 134 adenomyosis patients with dysmenorrhea were randomly assigned. Eight patients without any valid data at baseline were excluded and 126 patients were included in efficacy analysis (61 to mifepristone and 65 to placebo). The mean changes in VAS score were −6.63 (standard deviation [SD] 1.92) in mifepristone group and −0.95 (SD 1.75) in placebo group (p < 0.0001). The total effective and complete remission rates for dysmenorrhea in mifepristone group were significantly higher than those in placebo group ( 91.80% vs. 23.08% and 88.52% vs. 6.15%, respectively ). All the secondary outcomes showed significant improvements after mifepristone treatment for menstrual blood loss, the levels of hemoglobin and CA125, platelet count and uterine volume (P < 0.0001 for all). Safety analysis revealed no significant difference between two groups, and no serious adverse events were reported. Interpretation: Treatment with mifepristone resulted in significantly lower pain scores for adenomyosis patients with dysmenorrhea . Secondary outcomes were all met with a significant improvement with no new safety concerns and well-toleration. These data support that mifepristone could serve as a new treatment option for adenomyosis patients to relieve the symptoms with safety. Trial Registration: This trial is registered with ClinicalTrials.gov, NCT03520439. Funding/Support: This study was supported by National Key R&D Program of China (Grant number: 2017YFC1001202), National Natural Science Foundation of China (Grant numbers: 81974225, 81671429 and 81802591), Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation (Grant number: 19331203) and Jiaxing Municipal Public Welfare Research Project (Grant number: 2021AY30004). Declaration of Interest: None to declare. Ethical Approval: Ethical approval was obtained by the institutional review board or ethics committee at each investigational site before the initiation of the trial.

Predictors of response for elagolix with add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids

BACKGROUND:Uterine fibroids are one of the most common neoplasms found among women globally, with a prevalence of approximately 11 million women in the United States alone. The morbidity of this common disease is significant because it is the leading cause of hysterectomy and causes significant functional impairment for women of reproductive age. Factors including age, body mass index, race, ethnicity, menstrual blood loss, fibroid location, and uterine and fibroid volume influence the incidence of fibroids and severity of symptoms. Elagolix is an oral gonadotropin-releasing hormone receptor antagonist that competitively inhibits pituitary gonadotropin-releasing hormone receptor activity and suppresses the release of gonadotropins from the pituitary gland, resulting in dose-dependent suppression of ovarian sex hormones, follicular growth, and ovulation. In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 studies, treatment of premenopausal women with elagolix with hormonal add-back therapy demonstrated reduction in heavy menstrual bleeding associated with uterine fibroids.OBJECTIVE:This analysis aimed to evaluate the safety and efficacy of elagolix (300 mg twice a day) with add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate once a day) in reducing heavy menstrual bleeding associated with uterine fibroids in various subgroups of women over 6 months of treatment.STUDY DESIGN:Data were pooled from Elaris Uterine Fibroid-1 and Uterine Fibroid-2 studies, which evaluated premenopausal women (18–51 years) with heavy menstrual bleeding (>80 mL menstrual blood loss per cycle, alkaline hematin methodology) and ultrasound-confirmed uterine fibroid diagnosis. Subgroups analyzed included age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume (largest fibroid identified by ultrasound). The primary endpoint was the proportion of women with <80 mL menstrual blood loss during the final month and ≥50% menstrual blood loss reduction from baseline to final month. Secondary and other efficacy endpoints included mean change in menstrual blood loss from baseline to final month, amenorrhea, symptom severity, and health-related quality of life. Adverse events and other safety endpoints were monitored.RESULTS:The overall pooled Elaris Uterine Fibroid-1 and Uterine Fibroid-2 population was typical of women with fibroids, with a mean age of 42.4 (standard deviation, 5.4) years and a mean body mass index of 33.6 (standard deviation, 7.3) kg/m2 and 67.6% of participants being black or African American women. A wide range of baseline uterine and fibroid volumes and menstrual blood loss were also represented in the overall pooled study population. In all subgroups, the proportion of responders to the primary endpoint, mean change in menstrual blood loss, amenorrhea, reduction in symptom severity, and improvement in health-related quality of life were clinically meaningfully greater for women who received elagolix with add-back therapy than those who received placebo and consistent with the overall pooled study population for the primary endpoint (72.2% vs 9.3%), mean change in menstrual blood loss (−172.5 mL vs −0.8 mL), amenorrhea (50.4% vs 4.5%), symptom severity (−37.1 vs −9.2), and health-related quality of life score (39.9 vs 8.9). Adverse events by subgroup were consistent with the overall pooled study population.CONCLUSION:Elagolix with hormonal add-back therapy was effective in reducing heavy menstrual bleeding associated with uterine fibroids independent of age, body mass index, race, ethnicity, baseline menstrual blood loss, fibroid location, and uterine and primary fibroid volume.

PCP49 - EXPLORING THE SENSITIVITY TO CHANGE OF THE SAMANTA QUESTIONNAIRE IN HEAVY MENSTRUAL BLEEDING: THE SAMIRA STUDY

Despite the important impact of Heavy Menstrual Bleeding (HMB) in many women’s lives, its management is complex due to the inconvenience of the techniques to assess the real blood loss and the poor correlation between blood loss and women’s perception. A 6 item-questionnaire in Spanish language has been elaborated to address the need to develop an easy-to-handle validated tool to identify HMB cases: the SAMANTA questionnaire. It has shown good sensitivity and specificity to discriminate between women with and without HMB. The main objective of SAMIRA study is to explore, under routine gynaecological practice, if the SAMANTA questionnaire, designed to diagnose HMB, can also be sensitive to change in women with HMB who have been treated for 12 months with a chronic hormonal treatment under therapeutic indication in Spain. This is an observational, prospective and cohort study with a 12 month follow-up that will be carried out in Spain. The sensitivity to change of SAMANTA scale will be explored by estimating the change from baseline to final score in relation to the change in different clinical measurements such as duration of period, blood loss and presence of amenorrhea, and in comparison with patient’s and clinician’s global impressions of severity and change of menstrual bleeding. The SAMIRA study aims to go one step further in order to evaluate whether the SAMANTA questionnaire is also able to detect changes in menstrual blood loss in women with HMB. If the SAMANTA questionnaire shows a consistent behaviour with the rest of clinical measurements, it can be hypothesized that it might be useful for clinicians not only to screen for HMB but also to evaluate the change in HMB severity in patients under a hormonal treatment.

Safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system in women with cardiovascular disease.

We sought to examine the safety and efficacy of a 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS), and to evaluate the changes in biomarkers of infection, anemia and cardiovascular conditions after LNG-IUS insertion in women with cardiovascular disease. We prospectively followed women with a cardiovascular disease in whom a 52-mg LNG-IUS was inserted between 2009 and 2015. The primary outcome was the frequency of cardiovascular and gynecologic side effects due to the LNG-IUS over the year after LNG-IUS insertion. The secondary outcomes were the changes in menstrual blood loss and biomarkers, e.g., white blood cell count and the levels of C-reactive protein, hemoglobin and brain natriuretic peptide. We also evaluated the 24-month continuation rate of LNG-IUS. A total of 34 women were prospectively followed-up, including two women with pulmonary hypertension. No cardiovascular side effects were identified during the 1 year after LNG-IUS insertion, other than one case of mild vasovagal reaction at insertion. Neither the white blood cell count nor the C-reactive protein value increased after LNG-IUS insertion. The menstrual blood loss was decreased in most subjects and the median hemoglobin levels increased significantly within 1 year after insertion (P < 0.001 and P = 0.002). Moreover, brain natriuretic peptide levels tended to decrease in correspondence with the hemoglobin elevation (P = 0.074). The 24-month LNG-IUS continuation rate was 97% (95% confidence interval 85-100). No clinically significant cardiovascular event was identified during the 1 year after 52-mg LNG-IUS insertion among women with cardiovascular disease. The 52-mg LNG-IUS may have specific favorable effects by decreasing the risk of iron deficiency anemia in these women.

Efficacy and Safety of Estradiol Valerate/Dienogest for the Management of Heavy Menstrual Bleeding: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase III Clinical Trial.

To investigate the efficacy and safety of estradiol valerate (EV)/dienogest (DNG) for the management of heavy menstrual bleeding (HMB) in Asian and non-Asian women desiring contraception. In this multicenter, double-blind, phase III study, women were randomized 2:1 to receive EV/DNG or placebo tablets daily for seven 28-day cycles. The primary endpoint was the absolute change in menstrual blood loss (MBL) volume between the run-in and efficacy phases (90 days each). Secondary endpoints included the proportion of women with successful treatment (i.e., no episodes of MBL ≥80 mL and a decrease of <50% in MBL), percent change in MBL from the run-in phase, and change in hemoglobin and serum ferritin levels. Adverse events (AEs) were monitored throughout the study. Of the 341 women (mean age 34.7 ± 7.7 years; 309 Asians, 32 non-Asians) randomized, 270 completed the study. Mean reduction in MBL volume from run-in phase was significantly greater with EV/DNG than placebo (366.75 mL vs. 149.14 mL; p < 0.0001), with ∼52% and 12% of women, respectively, experiencing successful treatment. Percent decrease in MBL volume from the run-in phase was significantly greater with EV/DNG than placebo (63.5% vs. 24.8%; p < 0.0001). Hemoglobin and serum ferritin levels were increased with EV/DNG compared with placebo. Study drug-related AEs were reported in 16.3% and 8.2% of women with EV/DNG and placebo, respectively, none of which were of severe intensity. EV/DNG may be a safe and effective option in the treatment of HMB in Asian and non-Asian women who desire contraception.

Pilot Study of the Mirabilis System Prototype for Rapid Noninvasive Uterine Myoma Treatment Using an Ultrasound-Guided Volumetric Shell Ablation Technique

Study ObjectiveThe primary objective of this pilot study was to evaluate the safety and acute tissue ablation efficacy of a transabdominal high-intensity focused ultrasound (HIFU) prototype device that uses ultrasound imaging guidance for rapid noninvasive ablation of uterine myomas. The secondary objective was to assess preliminary myoma-related symptom improvement and myoma volume reduction at 3 to 6 months post-treatment in subsets of patients. DesignMulticenter prospective single-arm pilot study (Canadian Task Force classification II-2). SettingUniversity-affiliated teaching hospital and private community hospital. PatientsWomen with a diagnosis of symptomatic uterine myomas planning to undergo hysterectomy. InterventionsSeventy-three women underwent transabdominal ultrasound-guided HIFU treatment using a volumetric ablation technique referred to as “shell ablation,” in which the HIFU energy is deposited in patterns that partially encapsulate the peripheral region of the targeted myoma(s). Patients were divided into 2 sequential cohorts, the development cohort (the first 37 patients treated) and the validation cohort (the final 36 patients treated). Development cohort treatments were performed for dose-ranging purposes to identify the optimum HIFU treatment parameters, whereas the validation cohort treatments were performed to validate these final settings. Sixty-five patients (89.0%) received only prophylactic oral, sublingual, or intramuscular analgesia before treatment, sometimes with oral anxiolytics. The remaining 8 patients (11.0%) were anesthetized before treatment. Sixty-seven patients (91.8%) then had scheduled hysterectomies between 0 and 179 days after treatment completion. Adverse events were monitored until study exit, which ranged from 10 to 191 days post-treatment. Measurements and Main ResultsThe primary efficacy endpoint measured in all 73 patients was the nonperfused volume (NPV) of tissue produced, which was assessed between 0 and 7 days post-treatment either by tissue sectioning after hysterectomy or by gadolinium-enhanced magnetic resonance imaging. Secondary efficacy endpoints were also measured in subsets of patients who were prospectively scheduled for delayed hysterectomies: Changes in menstrual blood loss (MBL), symptom severity (SS), and quality of life (QOL) scores were assessed using validated techniques at 3 months post-treatment in 10 patients and changes in treated myoma volume were assessed using magnetic resonance imaging at 3 to 6 months post-treatment in 14 patients. In all 73 patients, there were no reports of any serious adverse device effects, including no damage to any extrauterine collateral tissues or the abdominal skin. In the development cohort, a mean NPV of 17.9 ± 24.9 cm3 (range, 0–123.0) was produced in a mean total treatment time of 4.9 ± 2.4 minutes (range, 1.1–11.3). These metrics improved in the validation cohort, where a mean NPV of 44.9 ± 58.5 cm3 (range, 0–284.7) was produced in a mean total treatment time of 3.6 ± 2.1 minutes (range, 1.5–9.5). In the subsets of patients with data available, there was a significant improvement in QOL score (median, 16.5 point increase; p = .011), an improving trend in SS score (median, 13.5 point decrease; p = .254), and a significant improvement in treated myoma volume (mean, 24.0% decrease; p = .013). In 8 patients who had above-average MBL scores at baseline and regular menstrual cycle lengths during follow-up, there was also a significant improvement in MBL score (median, 40.8% decrease; p = .035). ConclusionUltrasound-guided HIFU ablation with the prototype device demonstrated an excellent safety profile and produced clinically relevant NPVs in a mean total treatment time of under 4 minutes using the final validated treatment settings. Short-term clinical efficacy metrics assessed in subsets of patients were encouraging, and larger studies should be conducted to confirm these results (ClinicalTrials.gov, NCT01946178).

Medical management of heavy menstrual bleeding: a comprehensive review of the literature.

Heavy menstrual bleeding (HMB) is a common complaint among reproductive-aged women, which negatively affects their health as well as their social, professional, and family lives. Modern medical management usually provides effective control of HMB irrespective of the underlying cause. Surgical interventions should be reserved for women with significant pelvic pathology and those unresponsive to medical therapy. The aim of this review was to provide a comprehensive summary of the efficacy and safety of available medical treatments of HMB. A comprehensive MEDLINE and EMBASE literature search was undertaken using selected terms associated with HMB to identify clinical studies published before March 20, 2013, that reported changes in menstrual blood loss in women receiving medical intervention. The effectiveness of treatments to reduce HMB due to endometrial dysfunction in descending order was as follows: (1) the levonorgestrel-releasing intrauterine system (LNG-IUS) (initial release rate of 20 μg of LNG per 24 hours), (2) combined hormonal contraceptives (oral or transvaginal), (3) tranexamic acid, and (4) long-course oral progestogens (≥3 weeks per cycle). The LNG-IUS was found to reduce HMB due to some structural causes (leiomyomas and adenomyosis). The reduction in menstrual blood loss achieved with nonsteroidal anti-inflammatory drugs and short-course oral progestogens (≤14 days per cycle) is less impressive but may be sufficient for women who have marginally increased blood loss. For women not seeking pregnancy, the LNG-IUS is the first-line medical therapy for HMB, with combined hormonal contraceptives as second choice. For other women, fewer effective options exist.

Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest

ABSTRACTObjectives To evaluate the efficacy of oestradiol valerate/dienogest (E2V/DNG) for the treatment of heavy and/or prolonged menstrual bleeding without organic pathology based on the analysis of data from two identically designed double-blind, randomised studies.Methods Women aged ≥ 18 years with heavy and/or prolonged menstrual bleeding were randomised to E2V/DNG (n = 269) or placebo (n = 152) for 196 days. Objective changes in menstrual blood loss (MBL) volume were assessed using the alkaline haematin method.Results After six months of treatment, median MBL decreased by 88% with E2V/DNG compared with 24% with placebo. The greatest reduction was achieved at the first withdrawal bleed after treatment initiation and it was sustained with no loss of effect throughout treatment.Conclusion E2V/DNG was more effective than placebo in reducing MBL in women with heavy and/or prolonged menstrual bleeding without organic pathology. The reduction was largely achieved as early as the first withdrawal bleed, with further gradual improvement throughout treatment.

The levonorgestrel-releasing intrauterine system provides a reliable, long-term treatment option for women with idiopathic menorrhagia

Idiopathic menorrhagia (IM) is an important clinical challenge. The levonorgestrel-releasing intrauterine system (LNG IUS) provides an effective treatment option as shown by multiple small clinical studies. In this analysis of combined data, we describe the time course of relative change in menstrual blood loss (MBL) from baseline up to 5years. The results of two different methods to assess MBL were merged. We pooled and analyzed five prospective, randomized clinical studies investigating the effect of the LNG IUS on IM in a total of 230 women. Four studies assessed MBL by using the pictorial blood loss assessment chart (PBAC) and one study used the alkaline hematin method. We gathered data on percentage change from baseline after 3 and 6months, and annually up to 5years. In addition we analyzed results on hemoglobin (Hb) and serum ferritin (S-Fe). MBL data was available after 3 and 6months from 165 and 152 patients, respectively, and after 1year from 51 patients. Long-term data up to 3 and 5years was available for 28 and 10 patients, respectively. Not all studies provided data for all time points. Median (interquartile range) MBL decreased from baseline by -84.5% (-93.3; -63.6%) after 3months, by -92.9% (-97.6; -81.1%) and by -93.8% (-98.8; -81.1%) after 6months and 1year, respectively (P<0.0001, all time points). After 2and 5years the decrease was more than 96%. In parallel, Hb and S-Fe increased significantly. The LNG IUS rapidly induced clinically and statistically significant long-term reductions in MBL, paralleled by increases in Hb and S-Fe levels.

Menorrhagia Impact Questionnaire: assessing the influence of heavy menstrual bleeding on quality of life

Objective:Menorrhagia, or heavy menstrual bleeding (HMB), has a negative impact on women’s quality of life (QOL). The objective was to develop, validate, and assess the performance of a disease-specific patient-reported outcome (PRO) measurement instrument for HMB (the Menorrhagia Impact Questionnaire [MIQ]).Research design and methods:The MIQ was designed to measure the effect of HMB on a woman’s self-assessment of menstrual blood loss (MBL), limitations in social/leisure activities, physical activities, and ability to work. Meaningfulness of these observed MBL changes were also measured. The development and psychometric validation of the MIQ was performed utilizing data from a long-term safety study of tranexamic acid (Lysteda*Lysteda is a registered trade name of Ferring Pharmaceuticals Inc., Parsippany, NJ, USA.), with comparison to an age-matched normal control group recruited from the general population. Performance of the MIQ was also evaluated using data from a six-cycle, randomized, double-blind, clinical study of tranexamic acid for the treatment of HMB. Correlations and sensitivity of each pertinent MIQ item to the treatment-induced changes in MBL were assessed, and the minimally important differences (MID) for the individual MIQ items were determined.Results:The psychometric properties of the MIQ were fully validated. Correlations between individual MIQ items and changes in MBL were statistically significant (p < 0.001). A clear differentiation between tranexamic acid and placebo groups confirmed sensitivity of the MIQ and its ability to detect treatment-induced changes in MBL. MIDs were estimated for the individual MIQ items, with sensitivities and specificities in the 64–79% and 63–82% ranges using receiver operating characteristic (ROC) curve analyses, respectively. MIDs were found to be equal to or greater than 0.5. Statistically significant treatment differences were also observed for the proportions of subjects achieving at least 1-point improvement in MIQ scores.Conclusion:The MIQ contains validated constructs important to women with HMB.Clinical trial registration: NCT00113568 and NCT00386308 (ClinicalTrials.gov ID)Trial registration: ClinicalTrials.gov identifier: NCT00113568.Trial registration: ClinicalTrials.gov identifier: NCT00386308.

Levonorgestrel-Releasing Intrauterine System or Medroxyprogesterone for Heavy Menstrual Bleeding

To compare the efficacy and safety of the levonorgestrel-releasing intrauterine system and oral medroxyprogesterone acetate in the treatment of idiopathic heavy menstrual bleeding. In this multicenter, randomized, controlled study, women aged 18 years or older with heavy menstrual bleeding (menstrual blood loss 80 mL or more per cycle) were randomly assigned to six cycles of treatment with either levonorgestrel-releasing intrauterine system or oral medroxyprogesterone acetate (10 mg daily for 10 days beginning on day 16 of each cycle). The primary efficacy variables were the absolute change in menstrual blood loss from baseline to end of study and the proportion of women with successful treatment (defined as menstrual blood loss less than 80 mL and a 50% or greater reduction in menstrual blood loss from baseline). Of 807 women screened, 165 were randomly assigned to treatment (levonorgestrel-releasing intrauterine system n=82, oral medroxyprogesterone acetate n=83). At the end of the study, the absolute reduction in median menstrual blood loss was significantly greater in the levonorgestrel-releasing intrauterine system group (-128.8 mL, range -393.6 to +1242.2 mL) than in the medroxyprogesterone acetate arm (-17.8 mL, range -271.5 to +78.6 mL, P < .001), and the proportion of women with successful treatment was significantly higher for the levonorgestrel-releasing intrauterine system (84.8%) than for medroxyprogesterone acetate (22.2%, P < .001). In women with idiopathic heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system reduces menstrual blood loss more effectively and has a higher likelihood of treatment success than oral medroxyprogesterone acetate. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00360490. I.

A Canadian, Multicentre Study Comparing the Efficacy of a Levonorgestrel-releasing Intrauterine System to an Oral Contraceptive in Women With Idiopathic Menorrhagia

ObjectivesTo evaluate the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) compared with a combined oral contraceptive containing 1 mg norethindrone acetate and 20 μg ethinyl estradiol (OC1/20) in reducing menstrual blood loss (MBL) in women with idiopathic menorrhagia. MethodsA prospective, randomized, open-label study was conducted in nine centres in Canada. Healthy women over 30 years of age suffering from idiopathic menorrhagia were treated either with LNG-IUS (n = 20) or with OC1/20 (n = 19) over 12 months. The primary endpoint was the change in MBL from baseline to 12 months. Secondary endpoints included treatment success (defined as a MBL score < 100 after 12 months), hemoglobin levels, and the menorrhagia severity score. ResultsIn both treatment groups, MBL decreased significantly from baseline to 12 months (P < 0.001). For the primary endpoint, the MBL score decreased significantly more in the LNG-IUS group (median from 228 to 13, mean percent change–83%) compared to the OC1/20 group (median from 290 to 72; mean percent change–68%) (P = 0.002) after 12 months.In the LNG-IUS group, 80% of subjects had treatment success compared with 36.8 % in the OC1/20 group (P < 0.009).Both treatments increased hemoglobin concentrations significantly between baseline and 12 months. The menorrhagia severity score was consistently lower in the LNG-IUS group at all study time points and was significantly lower (P = 0.045) at six months. Both treatments were well tolerated. ConclusionBoth the LNG-IUS and the combined oral contraceptive effectively decreased menstrual blood loss in women with idiopathic menorrhagia. The overall clinical benefit was more pronounced with LNG-IUS than with OC1/20.

Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts

To compare the efficacy and tolerability of the levonorgestrel intrauterine system (LNG IUS) with mefenamic acid in the management of objective idiopathic menorrhagia. Phase III, Single centre, open, randomised, comparative, parallel group study. District General Hospital in the United Kingdom. Fifty-one women with objective menorrhagia. Twenty-five women randomised to receive the LNG IUS and 26 to oral mefenamic acid for six cycles. Change from baseline in menstrual blood loss (MBL), total menstrual fluid loss (TMFL) and pictorial blood loss assessment chart (PBAC) score at the third and sixth cycle of treatment. After six cycles the median menstrual blood loss was 5 mL in the LNG IUS group and 100 mL in the mefenamic acid group (P < 0.001). Median TMFL was 27 mL in the LNG IUS group and 157 mL in the mefenamic acid group (P < 0.001). Median PBAC score was 25 in the LNG IUS group and 159 in the mefenamic acid group. Changes in menstrual blood loss correlated strongly to changes in TMFL (r= 0.88) but PBAC correlated less well to blood loss and total fluid loss (r= 0.53 and r= 0.58). Both the LNG IUS and mefenamic acid significantly decreased menstrual blood loss, TMFL and PBAC scores. The LNG IUS produced greater reductions in all parameters than mefenamic acid. Comparison of the different measurements suggests that TMFL assessment may be an easier and a more relevant measure of symptom severity than menstrual blood loss.

The safety and efficacy of MenoTreat, a new balloon device for thermal endometrial ablation.

An evaluation of the performance and safety of the prototype of a new device, MemoTreat (Atos Medical) for thermal endometrial balloon ablation in patients with menorrhagia. The evaluation was performed at four Swedish hospitals. In total 51 consecutive, premenopausal patients, suffering from menorrhagia due to benign causes and not responding to conventional treatment, were treated between March 1997 and March 1998. The treatment entailed heated (85 degrees C) sterile saline circulated in a uterine balloon at a treatment pressure of 200 mmHg for 11 minutes. The procedure was performed mainly under general anesthesia and no pre-treatment endometrial thinning was performed. A validated pictorial assessment technique was used to evaluate changes in menstrual blood loss before and after treatment. Changes in quality of life and severity of dysmenorrhea were also evaluated. Data analysis was based on the 'intention to treat' method. The success rate in terms of a 50% reduction in menstrual bleeding was 84.3% at 6 months after treatment. Five patients became amenorrheic. The quality of life assessment showed substantial improvement and the severity of dysmenorrhea was markedly reduced. No intra-operative treatment complications occurred and the post-treatment morbidity was similar to that reported for other similar treatment methods. MenoTreat significantly reduced menstrual bleeding in menorrhagic patients, with a concomitant improvement in quality of life. The findings in this study resulted in a redesigned device with a thinner balloon catheter, improved cervical protection and treatment temperatures kept at a constant level.

Serosal and Endometrial Reconstitution During Myomectomy

Context : Myomectomy is usually performed when uterine fibroids are associated with infertility. Serosal and endometrial reconstitution are some of the subtle challenges that the gynaecologist has to deal with during myomectomy, in an attempt to minimise postoperative pelvic and intrauterine adhesions. Objective : This study was conducted to evaluate the effect of careful apposition of the serosa and endometrium on subsequent development of post-myomectomy pelvic and intrauterine adhesions and to assess the effect of resection of redundant endometrium on subsequent menorrhagia. Study Design, Setting, and Subjects : A review of 17 patients with previous myomectomy who eventually had a subsequent laparotomy for various indications between June 1992, and July 1998 in the University College Hospital, Ibadan was carried out. Main Outcome Measures : Operative findings at myomectomy, as well as therapeutic procedures performed on them were recorded. Patients' observation of changes in menstrual blood loss postoperatively was also recorded. The presence of pelvic adhesions at re-laparotomy and intrauterine adhesions on hysterosalpingography in those who had endometrial reconstitution was also noted. Results : Continuous closure was found to be beneficial in all cases of serosal defects. Excision of redundant endometrium in 11 women was associated with subjective reduction of menorrhagia in 9 of them. Conclusion : It is advisable that gynaecological surgeons strive to minimise areas of visceral trauma, ischaemia and abrasion during myomectomy. (Tropical Journal of Obstetrics and Gynaecology, 2001, 18(1): 16-18)