Management Of Heavy Menstrual Bleeding Research Articles

Women and girls with inherited bleeding disorders: Focus on haemophilia carriers and heavy menstrual bleeding.

Raising awareness and improving recognition, accurate classification, and enhanced access to new treatments represent current key challenges for carriers of haemophilia. Women and girls carrying genes for haemophilia often experience significant bleeding and/or low factor levels. The bleeding associated with female haemophilia is frequently overlooked, has a weak correlation with factor levels, and manifests differently than in males, with heavy menstrual bleeding being a predominant symptom. Recent changes in terminology now allow the diagnosis of haemophilia in females with low factor levels and differentiate between symptomatic and asymptomatic carriers of the gene. Observations from real-world experiences and limited clinical trial data have highlighted the positive impact of various new haemophilia treatments for women and girls with clotting factor deficiencies. There is an urgent need for initiatives that increase their access to these treatments and encourage well-designed clinical trials focusing on female-specific outcomes. In women with inherited bleeding disorders, early recognition and optimal management of heavy menstrual bleeding are crucial. However, treatment options and guidance from high-quality clinical trials are currently insufficient. Menstrual health assessment should be a regular part of monitoring women and girls with inherited bleeding disorders throughout their lives, emphasizing the importance of gathering data to improve future management.

Obesity and menstrual disorders.

Obesity is a growing public health concern and is associated with a range of menstrual disorders, including heavy menstrual bleeding, oligomenorrhea, dysmenorrhea, and endometrial pathology. Investigations may be more logistically challenging in those in the population with obesity, and because of the heightened risk of endometrial malignancy, there should be a low threshold for biopsy to exclude endometrial hyperplasia. Although treatment modalities for women with obesity are broadly similar to those with a normal BMI, additional consideration must be given to the risks associated with estrogen in obesity. Outpatient management of heavy menstrual bleeding is a developing field and outpatient treatment modalities are preferable in the population with obesity to avoid the morbidity associated with anesthetics.

12. Needs Assessment: Knowledge and Confidence of ObGyn Residents in the Evaluation and Management of Heavy Menstrual Bleeding due to Bleeding Disorders

12. Needs Assessment: Knowledge and Confidence of ObGyn Residents in the Evaluation and Management of Heavy Menstrual Bleeding due to Bleeding Disorders

Management of heavy menstrual bleeding in women with bleeding disorders in a tertiary care center

BackgroundHeavy menstrual bleeding (HMB) affects a significant number of women with bleeding disorders and has a negative impact on their quality of life. ObjectiveThis retrospective study examined the management of patients with inherited bleeding disorders who used medical treatments, alone or in combination, for HMB. MethodsChart review was performed on women attending the Women with Bleeding Disorders Clinic in Kingston, Ontario, between 2005 and 2017. Data collected included patient demographics, the reason for presentation and diagnosis, medical history, treatments, and patient satisfaction. ResultsOne hundred nine women were included in this cohort. Of these, only 74 (68%) were satisfied with medical management, and only 18 (17%) with first-line therapy. Treatments included combined contraceptives (oral pill, transdermal patch, and vaginal ring), progesterone-only pills, tranexamic acid, 52-mg levonorgestrel intrauterine system (LIUS), depomedroxyprogesterone acetate, and desmopressin, either alone or in combination. Satisfactory control of HMB occurred most often with the LIUS. ConclusionIn this cohort, managed in a tertiary care Women with Bleeding Disorders Clinic, only 68% of patients had successful control of HMB with medical treatment, and a minority were satisfied with first-line therapy. These data clearly highlight the need for additional research, including treatment approaches and novel therapies for this population.

Development of relugolix combination therapy as a medical treatment option for women with uterine fibroids or endometriosis

Treatment of uterine fibroids (UF) and endometriosis (EM) has relied on the surgical skills of gynecologists to improve symptoms and potentially alter the course of these debilitating diseases. Medical management of symptoms for both diseases leverages combined hormonal contraceptives used off label as a first-line treatment, with nonsteroid anti-inflammatory drugs and opioids to manage pain as needed. Gonadotropin-releasing hormone (GnRH) receptor agonists (peptide analogs) have been used as short-term therapy to manage severe symptoms of UF or EM, treat anemia, and reduce fibroid size before surgery. The introduction of oral GnRH receptor antagonists opened the door for the development of new treatment options for UF, EM, and other estrogen-driven diseases. Relugolix is an orally active, nonpeptide, GnRH receptor antagonist that competitively binds to GnRH receptors, preventing the release of follicle-stimulating hormone and luteinizing hormone (LH) into the systemic circulation. In women, the reduction in follicle-stimulating hormone concentrations prevents natural follicular development, suppressing ovarian production of estrogen, and together with reductions in LH concentrations, prevent ovulation, corpus luteum formation, and, thereby, the production of progesterone (P). By reducing circulating concentrations of estradiol (E2) and P, relugolix improves heavy menstrual bleeding and other symptoms associated with UF and moderate to severe pain associated with EM, including dysmenorrhea, nonmenstrual pelvic pain (NMPP) and dyspareunia. However, as monotherapy, the use of relugolix is associated with signs and symptoms of a hypoestrogenic state, including bone mineral density loss and vasomotor symptoms. The clinical development of relugolix incorporated the addition of a 1 mg dose of E2 and a 0.5-mg dose of norethindrone acetate (NETA) to achieve systemic E2 concentrations that remain in a therapeutic range while mitigating the risk for bone mineral density loss and vasomotor symptoms, enabling the longer-term treatment and reducing the impact of symptoms on quality of life, and potentially delaying or preventing the need for surgery. Relugolix 40 mg in combination with estradiol (E2) 1 mg and NETA 0.5 mg as a single fixed-dose combination tablet (relugolix combination therapy [relugolix-CT]) approved in the United States as MYFEMBREE is the first and only once daily oral GnRH antagonist combination therapy indicated for the management of heavy menstrual bleeding associated with UF and moderate to severe pain associated with EM. In the European Union (EU) and the United Kingdom (UK), relugolix-CT is approved as RYEQO for the management of symptoms associated with UF. In Japan, relugolix 40 mg, as monotherapy, was the first GnRH receptor antagonist approved to improve symptoms associated with UF or pain associated with EM under the brand name RELUMINA. In men, relugolix suppresses testosterone production. Relugolix 120 mg (ORGOVYX) was developed by Myovant Sciences and is approved in the United States, EU, and UK as the first and only oral androgen-deprivation therapy for the treatment of advanced prostate cancer. This review is focused on the development of relugolix and relugolix-CT in women's health indications.

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids.

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo®; Myfembree®) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.

High Prevalence of Congenital Factor VII (FVII) Deficiency in Adolescent Females with Heavy Menstrual Bleeding and Iron Deficiency Anemia

To examine the clinical characteristics and prevalence of congenital bleeding disorders (CBDs), with emphasis on congenital factor VII (FVII) deficiency and other rare bleeding disorders, in adolescent and young adult females referred to a hemophilia treatment center (HTC) for evaluation and management of heavy menstrual bleeding (HMB) and iron deficiency anemia (IDA) DESIGN: In this single-center retrospective study, we reviewed the clinical characteristics and prevalence of CBDs in postmenarchal females, younger than 22 years of age, referred to an HTC from 2015 to 2021 for evaluation of HMB with or without IDA. One hundred females, with a mean age of 15 years (range 9-20 years), met initial study criteria, and 95 were included in the final analysis. Forty-five (47%) females were ultimately diagnosed with a CBD. The most prevalent diagnoses were FVII deficiency and type 1 von Willebrand disease (VWD) (42.3%, n=19 each). Forty-two percent of patients with FVII deficiency had a low-for-age FVII activity level, 21.1% were only positive for the FVII R353Q variant associated with borderline FVII levels, whereas 36.8% had both a low-for-age FVII activity level and a positive R353Q variant. Eighty percent of patients with a CBD were found to have relatives with abnormal bleeding symptoms. Congenital FVII deficiency is prevalent among female adolescents experiencing HMB with or without IDA. In addition to VWD, evaluation for this specific factor deficiency should be considered as part of the initial CBD workup. Presence of abnormal bleeding history in the family could also help to predict presence of a CBD.

Qurṣ-i-Shibb: A review on polyherbal Unani formulation in the management of Kathrat-i-Ṭamth (HMB)

Heavy flow during menstruation is called Menorrhagia or Heavy Menstrual Bleeding, is generally referred to excessive bleeding, either in duration or quantity of blood loss or both (> 8 days and/or >80 ml) at regular intervals. It can be associated with several conditions, including problems with the uterus, hormonal problems, or other conditions. While abundant bleeding may make it difficult to participate in normal daily life at certain times. But currently Several drugs and Hysterectomy is recommended for the treatment of HMB that has different side effects as well as gastrointestinal symptoms, liver disease, obesity, hypoestrogenic state and thromboembolic diseases. In classical texts Qurṣ-i-Shibb is used in the management of Kathrat-i-Ṭamth (Heavy Menstrual Bleeding) as this formulation has pharmacological activity such as ḥābis al-dam (haemostatic or haemostyptic), qābiḍ (astringent), mujafif (siccative), mugharrī (glutinous) and mubarrid (refrigerant). So, this review aims to explore the role of Qurs-i-Shibb in the management of Heavy Menstrual Bleeding. The ingredients of Qurs-i-shibb are shibb-i-yamāni, dam al-khwayn, gulnār each of them 10.5 gram, katīra 21 gram, samagh-i-ʻarabī 7 gram. These drugs having the properties of ḥābis al-dam, qābiz, mujaffif, mugharrī and mubarrid produce vasoconstriction and reduce heavy bleeding. The granules were formulated into 500 mg tablets. Three tablets thrice daily for 5days will help in reducing the bleeding.
 Keyword: Kathrat-i-ṭamth; Heavy menstrual bleeding; Qurṣ-ī-Shibb; hemostatic, astringent.

An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women

ABSTRACT Introduction Uterine Fibroids (UFs) are the most predominant benign tumor in women who are coming of reproductive age, and causes intense economic load priced in billions of US dollars. Historically, surgery has been the main definitive treatment, albeit less attractive nowadays, especially for women with future fertility plans. Therefore, studies to explore the pharmacological treatment options are increasing especially as those that are currently available are limited for short-term use only. Areas covered This drug evaluation features the clinical results from previous and ongoing studies of relugolix, in combination with the add back therapy of estradiol (E2) and norethindrone acetate (NETA), as a novel, orally administered, nonpeptide antagonist of gonadotropin-releasing hormone (GnRH) for the management of heavy menstrual bleeding (HMB) in premenopausal women with UFs. Expert opinion The combination of relugolix/E2/NETA is an encouraging, well-tolerated and noninvasive pharmacological option for UFs patients. Relugolix induced a concentration-dependent decrease in HMB. However, it should be used with hormonal add-back therapy (E2+ NETA) to avoid induced hypoestrogenic side effects, importantly bone mineral density loss. Moreover, symptoms will likely resume shortly after the termination of the relugolix combination administration.

Evaluation of the efficacy of levonorgestrel intrauterine system in the management of heavy menstrual bleeding: An analytical observational study

Background: Heavy menstrual bleeding (HMB) poses threat to the quality of life among women. To prevent HMB, the levonorgestrel-releasing intrauterine system (LNG-IUS) is a well-known nonsurgical, long-performing, and alternative method. Objectives: The objective of this study was to determine the efficacy of LNG-IUS in women with HMB through an analytical observational study. Materials and Methods: This study was performed among 60 patients who visited the gynecology and obstetrics outpatient department (OPD) at the Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital (IPGMER and SSKMH), Kolkata, West Bengal, India from May 2019 to April 2020 due to HMB. The mean demographic and clinical profiles were evaluated, and comparative analysis was performed for hemoglobin (Hb), spotting, pain, and endometrial thickness on day 0 and follow-up 3 months, 6 months, and 12 months. Results: The mean age of patients was 37.77 ± 4.58 years was obtained. The Hb level was significantly (P < .001) increased, whereas pictorial blood loss assessment chart (PBAC) score, endometrial thickness, spotting, and pain were significantly (P < .01 and P < .001) reduced. The majority of patients had pallor, but the rates of spontaneous expulsion and hysterectomy were observed lower after using LNG-IUS among studied patients. Conclusion: the usage of LNG-IUS is potential in the treatment of HMB in women, which may lead to a better quality of life. This can be the alternative to hysterectomy and oral pills for long-term use. It is suggested in a future study with larger sample size and multicentric approach to minimize hospital biasness.

Mirena: Just a contraceptive device? or A modality with diverse clinical applications !

Abnormal uterine bleeding is the most frequently encountered complaint of the reproductive-age women. Heavy menstrual blood loss is responsible for interfering with women's physical, emotional, social, and quality of life. Levonorgestrel-releasing intrauterine device (LNG-IUS) is a highly effective reversible form of contraception. Besides this, its role in the treatment of heavy menstrual bleeding (HMB), endometrial hyperplasia, early-stage endometrial cancers, and endometrial protection as a part of hormone replacement therapy (HRT) is very well studied. This review will revisit the role of LNG-IUS as a nonsurgical option in the management of HMB.

Management of heavy menstrual bleeding in Australian general practice: An analysis of BEACH data.

The 'Heavy menstrual bleeding (HMB) clinical care standard' was released in October 2017. The aim of this study was to determine the rate and management of HMB by Australian general practitioners (GPs) prior to release of the Standard. Data collected between April 2000 to March 2016 (inclusive) in the Bettering the Evaluation and Care of Health program were analysed for HMB management. The rate at which GPs managed HMB increased over the study period. The combined oral contraceptive pill was the most frequently prescribed treatment, except among women aged 45-54 years. There were low prescribing/insertion rates of the levonorgestrel intrauterine system (LNG-IUS) for women aged 25-54 years, and none for patients aged12-24 years. Improved understanding of patient and GP perspectives, and further education and training, could increase use of the LNG-IUS and other pharmaceutical treatments where appropriate, as recommended by the HMB clinical care standard.

Managing Abnormal Uterine Bleeding: A Comparative Study of Modified Thermal Balloon Ablation and Hysterectomy

Objective: To compare the outcome of modified thermal balloon ablation and hysterectomy for management of heavy menstrual bleeding in terms of frequency of patient satisfaction. Methods: All women aged between 35 to 45 years with heavy menstrual bleeding and who have completed their family were selected for the study. All 267 patients fulfilling inclusion criteria were recruited with uterine length less than 12cm, without any intrauterine pathology and normal endometrial biopsy. Results: Group A Patients underwent hysterectomy and patient's satisfaction rate was 91.3% (126/138). Group B patients underwent modified thermal balloon ablation and patient's satisfaction rate was 82 .6% (114 / 138). Conclusion: In the management of heavy menstrual bleeding, results of hysterectomy and modified thermal balloon ablation are comparable to each other in terms of achievement of patient's satisfaction especially when we have to choose between definitive and conservative surgical options.

Concomitant use of combined hormonal contraceptives and antifibrinolytic agents for the management of heavy menstrual bleeding: A practice pattern survey

IntroductionConcomitant antifibrinolytic agents and combined hormonal contraceptives (CHC) have been anecdotally used to manage refractory heavy menstrual bleeding (HMB). Yet, there remains uncertainty among clinicians regarding the safety of this therapeutic option as concomitant CHC is listed as a contraindication to tranexamic acid use in the United States. AimTo describe current treatment practices and physician-reported safety and effectiveness of concomitant antifibrinolytics and CHCs. MethodsWe surveyed clinician members of the Hemostasis and Thrombosis Research Society and the Foundation of Women and Girls with Blood Disorders using a web-based survey. We also shared the survey link on Twitter. ResultsOf the 224 respondents who completed the survey, 214 treated women of reproductive age with HMB. Of the 214 respondents, 138 (64%) had treated at least 1 woman with concomitant antifibrinolytic agents and CHCs in the past 12 months. Over half of these respondents (n = 77, 57%) reported that at least 50% of women had resolution of refractory HMB. One respondent reported an arterial or venous thrombotic event that occurred in 1 woman. ConclusionWe found that the use of concomitant CHCs and antifibrinolytic agent for refractory HMB is prevalent, appears to be efficacious and is relatively safe. Further research is warranted.

Complication Rates after Endometrial Ablation in Ontario: A Cohort Analysis of 76 446 Patients

Endometrial ablation (EA) is an alternative to hysterectomy for the management of heavy menstrual bleeding; however, EA is not without risk. Our objective was to determine complication rates in women undergoing EA in the province of Ontario over a 15-year time period. The primary outcome was a composite of multiple complications within 30 to 180 days of surgery. The secondary outcomes included mortality, length of hospital stay, hospital readmission, and emergency department visit within 30 days of discharge. Retrospective cohort study using Cochran-Armitage test for trend. Administrative data from the Canadian province of Ontario, assessing patients undergoing surgery in a publicly funded healthcare system. Women in Ontario undergoing a primary EA over a 15-year time period. The intervention was a primary EA. We assessed for genitourinary complication, fistula, gastrointestinal complication, pain, control of bleeding, blood transfusion, infectious complication, venous thromboembolism, fluid overload, thermal injury, and other injuries related to surgery. The secondary outcomes included 1-month and 6-month mortality, length of hospital stay, hospital readmission, and emergency department visit within 30 days of discharge. A total of 76 446 primary EAs were evaluated from 2002 to 2017, with the number of EAs per year increasing over the study period by 47%. Complications were seen in 4.8% of the cohort, with the complication rate being relatively stable over time. Although 6.2% of the cohort re-presented to the emergency department, <1% required readmission, and <0.05% died within 180 days. On multivariable analysis, the risk of complications increased with a preoperative diagnosis of other than bleeding (odds ratio [OR] 2.89; 95% confidence interval [CI], 2.61-3.21; p <.001), previous abdominal surgery (OR 1.42; 95% CI, 1.28-1.56; p <.001), and American Society of Anesthesiologists score 3+ (OR 1.37; 95% CI, 1.27-1.48; p <.001). Primary EA is associated with complications in <5% of the patients, with serious complications infrequent.

The endometrial response to modulation of ligand-progesterone receptor pathways is reversible

To study the impact of the progesterone receptor modulator (PRM), ulipristal acetate (UPA), on endometrial morphology and function. Cross-sectional. University Research Institute. Endometrial biopsies from 16 patients with heavy menstrual bleeding with a structurally normal uterus or in association with structural abnormalities identified on radiological imaging (fibroids, adenomyosis or a combination of fibroids and adenomyosis). Participants received UPA (5 mg once daily) for three 12-week courses, each separated by 4 weeks without treatment. Gene expression by real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and digital image analysis were analyzed to investigate the endometrial impact of modulation of progesterone receptor pathways upon expression of steroid receptors, steroid metabolizing enzymes, cell proliferation, and progesterone-regulated genes in the same patients at 3 time points: before, during, and after discontinuation of PRM treatment. Ulipristal acetate treatment resulted in increased messenger ribonucleic acid (mRNA) levels of steroid receptors compared with pretreatment secretory endometrium; decreased mRNA levels of 17- and 11-beta-hydroxysteroid dehydrogenases compared with pretreatment proliferative endometrium and pretreatment secretory endometrium; reduced cell proliferation compared with pretreatment proliferative endometrium; and altered mRNA levels of progesterone-regulated genes. A strong consistency between immunohistochemistry-digital image analysis and real-time quantitative reverse transcription polymerase chain reaction results was evident. Alterations in the mRNA levels and endometrial morphology returned to a pretreatment phenotype after the cessation of PRM exposure. The endometrial impact of the modulation of progesterone receptor pathways with PRM (UPA) treatment is reversible. Ulipristal acetate versus conventional management of heavy menstrual bleeding (UCON) trial (EudraCT 2014-003408-65; REC14/LO/1602).

Synthesis of [H‐3]‐ and [C‐14]‐labeled elagolix

Gonadotropin-releasing hormone (GnRH) receptor antagonists are an important class of compounds designed to block the pituitary gland from synthesizing follicle-stimulating hormone and luteinizing hormone for the treatment of sex hormone dependent disorders. Elagolix (ABT-620) is currently approved for the treatment of pain associated with endometriosis and as a combination with estradiol and norethindrone acetate is approved for management of heavy menstrual bleeding due to uterine fibroids. In order to support the development of elagolix, we prepared [3 H]elagolix for preclinical metabolism studies and [14 C]elagolix for environmental risk assessment studies.

Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women

ABSTRACT Introduction Uterine fibroids (UFs) are the most common benign tumor arising from myometrium of reproductive age women, with significant financial burden estimated in hundreds of billions of dollars. Unfortunately, there are limitations in available long-term treatment options. Thus, there is a large unmet need in the UF space for noninvasive therapeutics. Areas covered Authors reviewed the literature available for elagolix; an orally bioavailable, second-generation, non-peptide gonadotropin-releasing hormone (GnRH) antagonist recently approved by the US Food and Drug Administration (FDA) in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with UFs in premenopausal women. Expert opinion The utility of new-generation oral GnRH-antagonists, such as elagolix, relugolix and linzagolix, is offering a new potential opportunity for the future therapy of UFs: elagolix has been the most studied drug of this class for treating benign gynecological diseases, including endometriosis and UFs, for which it has been US FDA-approved in 2018 and 2020, respectively.

Medical Therapy for Fibroids: What Next for Ulipristal Acetate?

Ulipristal acetate (UPA) was introduced as a novel progesterone receptor modulator as effective therapy for symptomatic fibroids. Randomised clinical trials established its effectiveness in the management of heavy menstrual bleeding due to uterine leiomyomas. The trials did not find any significant evidence of clinical harm to the participants. Recently, however, there have been reports of liver injury necessitating liver transplant in women who have had UPA treatment. This has led to the suspension of UPA as one of the medical therapies in the treatment for uterine fibroids while the European Medicines Agency (EMA) conducts a review of liver injury risk with its use. The European Medicine Agency safety committee has advised that women should stop taking 5 mg UPA and that no new patients should commence treatment with the medicine until the ongoing review is completed. In this article, we review the rise of UPA as one of the emerging medical therapies for symptomatic uterine fibroids and the subsequent reports of adverse events leading to the suspension of its use.

Bleeding in Patients with Clinically Severe Von Willebrand Disease: Preliminary Results of Athn 9, a Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Severe Von Willebrand Disease (VWD)

Bleeding in Patients with Clinically Severe Von Willebrand Disease: Preliminary Results of Athn 9, a Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Severe Von Willebrand Disease (VWD)