Cause Of Heavy Menstrual Bleeding Research Articles

Treatment of uterine fibroid symptoms with relugolix combination therapy

Uterine fibroids are a common cause of heavy menstrual bleeding and pain. Treatment with the combination of relugolix (an oral gonadotropin-releasing hormonereceptor antagonist), estradiol, and norethindrone acetate, administered once daily, may have efficacy in women with uterine fibroids and heavy bleeding while avoiding hypoestrogenic effects. Methods. We conducted two replicate international, double-blind, 24-week, phase 3 trials involving women with fibroid-associated heavy menstrual bleeding. Participants were randomly assigned in a 1:1:1 ratio to receive once-daily placebo, relugolix combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate), or delayed relugolix combination therapy (40 mg of relugolix monotherapy, followed by relugolix combination therapy, each for 12 weeks). The primary efficacy end point in each trial was the percentage of participants with a response (volume of menstrual blood loss <80 ml and a ≥50% reduction in volume from baseline) in the relugolix combination therapy group, as compared with the placebo group. Key secondary end points were amenorrhea, volume of menstrual blood loss, distress from bleeding and pelvic discomfort, anemia, pain, fibroid volume, and uterine volume. Safety and bone mineral density were assessed.Result. A total of 388 women in trial L1 and 382 in trial L2 underwent randomization. A total of 73% of the participants in the relugolix combination therapy group in trial L1 and 71% of those in trial L2 had a response (primary end point), as compared with 19% and 15%, respectively, of those in the placebo groups (P<0.001 for both comparisons). Both relugolix combination therapy groups had significant improvements, as compared with the placebo groups, in six of seven key secondary end points, including measures of menstrual blood loss (including amenorrhea), pain, distress from bleeding and pelvic discomfort, anemia, and uterine volume, but not fibroid volume. The incidence of adverse events was similar with relugolix combination therapy and placebo. Bone mineral density was similar with relugolix combination therapy and placebo but decreased with relugolix monotherapy.Conclusions. Once-daily relugolix combination therapy resulted in a significant reduction in menstrual bleeding, as compared with placebo, and preserved bone mineral density in women with uterine fibroids.

Awareness of von Willebrand disease among gynecologists: Investigating the referral of women with heavy menstrual bleeding to hematologists.

SynopsisAwareness of bleeding disorders, including von Willebrand disease, as a cause of heavy menstrual bleeding is low among gynecologists/obstetricians, potentially delaying diagnosis and appropriate treatment.

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.

Systematic review and meta-analysis of the etiology of heavy menstrual bleeding in 2,770 adolescent females

BackgroundAdolescent heavy menstrual bleeding(HMB), menorrhagia or abnormal uterine bleeding commonly occur in adolescent women. The differential diagnosis can be challenging. The pneumonic: PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified), is commonly used but it does not stratify as to the likelihood of a disorder. We have sought to develop a probability-based differential diagnosis for Adolescent HMB, menorrhagia or abnormal uterine bleeding.MethodsA comprehensive literature search was conducted using PubMed, EMBASE, and SCOPUS databases. Case series describing adolescents from 10–19 years of age with HMB, menorrhagia or abnormal uterine bleeding was acceptable if: more than 10 patients were included; editorials, case reports, and secondary sources such as review articles, or book chapters were excluded. No language filter was used, but an English abstract was required. The etiology of HMB, menorrhagia or abnormal uterine bleeding, and the country of origin was extracted from articles that met inclusion criteria. Cumulative rate estimates were determined by Bayesian probability modeling.ResultsSeventeen full text articles were reviewed in detail; 2,770 patients were included. The most frequent causes of HMB were Ovarian Uterine Disorders (23.7%; 95% CredI 22–25.5%), Coagulation Disorders (19.4%; 95% CredI 17.8—21.1%), and Platelet Disorders (6.23%; 95% CredI 5.27–7.27%) with 45.9% (95% CredI 43.8—47.%9) of the cases of indeterminate origin.ConclusionsThe leading causes of HMB in healthy adolescent females were varied. The sub-analysis identified distinct etiologies, suggesting that multiple factors must be considered in the evaluation of HMB. While PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) provides us with a comprehensive picture of the possible causes of HMB in females, this systematic review assigns probabilities to the etiologies of HMB in adolescent females, providing physicians with a more focused and efficient pathway to diagnosis.

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.

Evaluation of adolescents with heavy menstrual bleeding using the International Society of Thrombosis Haemostasis- Bleeding Assessment Tool and The Pediatric Bleeding Questionnaire scores.

Heavy menstrual bleeding (HMB) is a common condition in adolescents. However, bleeding disorders are known to be one of the causes of HMB in adolescent girls, so they should be considered. Simple methods that can be used in primary health care are needed to determine whether patients have bleeding disorders. The aim of this study was to evaluate the bleeding score of patients admitted with HMB and to determine the diagnostic value of patients who were symptomatic but whose initial hemostatic tests were normal. A total of 113 adolescents with HMB and 20 healthy adolescent girls were included in the study. The Pediatric Bleeding Questionnaire (PBQ) and the International Society of Thrombosis Haemostasis-Bleeding Assessment Tool (ISTH-BAT) were used for evaluation. Overall, approximately 18% (n= 20) of the adolescents in the study were diagnosed with a bleeding disorder. The cut off value for the `clinically significant bleeding score` was found to be 3.5. The PBQ and ISTH-BAT can help distinguish a significant bleeding history from an otherwise trivial bleeding and can be included in the algorithm for the primary care of adolescents with HMB with suspected bleeding disorders.

Decreased Glycolysis at Menstruation is Associated with Increased Menstrual Blood Loss.

Heavy menstrual bleeding (HMB) is common and severely affects the quality of life of the afflicted women. While HMB is known to be caused by impaired endometrial repair after menstruation, its more proximate cause remains unknown. To investigate whether glycolysis plays any role in endometrial repair and thus HMB, we conducted two mouse experiments using a mouse model of simulated menstruation. We performed immunohistochemistry analyses of proteins involved in glycolysis as well aspro- and anti-inflammatory cytokines in endometrium from decidualized and non-decidualized uterine horns. We also assessed the extent of endometrial repair by staging endometrial morphology from decidualization to full repair using histological scoring of uterine sections and quantitated the amount of menstrual blood loss (MBL). In addition, we employed the scratch assay and the CCK-8 assay to evaluate the effect of glycolysis suppression on cellular migration and proliferation, respectively. Finally, we performed an immunohistochemistry analysis of HK2 in endometrium from women with adenomyosis who experienced either moderate/heavy or excessive MBL. We found that endometrial repair coincided with increased glycolysis in endometrium and glycolysis suppression delayed endometrial repair, resulting in increased MBL. Additionally, glycolysis suppression significantly inhibited the proliferative and migratory capability of endometrial cells, and disrupted normal endometrial repair even when hypoxia was maintained. Women with adenomyosis who experienced excessive MBL had significantly lower HK2 staining than those who experienced moderate/heavy MBL. Thus, our study highlights the importance of glycolysis as well as inflammation in optimal endometrial repair, and provides clues for the cause of HMB in women with adenomyosis.

Key issues in the management of adolescents and young women with heavy menstrual bleeding

Despite high prevalence of heavy menstrual bleeding (HMB) in adolescents and young women, most recommendations are not specific for this population, which makes the diagnosis and management challenging. Gynecologists should be able to establish underlying causes of HMB, which most common are nonstructural in adolescents, and the severity of bleeding, to provide early diagnosis, using appropriate therapy for improving quality of life and iron deficiency prevention. First line management consists of hormonal therapy approved for HMB treatment, capable to normalize menstrual blood loss and iron metabolism parameters.

Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy

BackgroundUterine fibroids are a common cause of heavy menstrual bleeding and pain. Treatment with the combination of relugolix (an oral gonadotropin-releasing hormone-receptor antagonist), estradiol, and norethindrone acetate, administered once daily, may have efficacy in women with uterine fibroids and heavy bleeding while avoiding hypoestrogenic effects.MethodsWe conducted two replicate international, double-blind, 24-week, phase 3 trials involving women with fibroid-associated heavy menstrual bleeding. Participants were randomly assigned in a 1:1:1 ratio to receive once-daily placebo, relugolix combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate), or delayed relugolix combination therapy (40 mg of relugolix monotherapy, followed by relugolix combination therapy, each for 12 weeks). The primary efficacy end point in each trial was the percentage of participants with a response (volume of menstrual blood loss <80 ml and a ≥50% reduction in volume from baseline) in the relugolix combination therapy group, as compared with the placebo group. Key secondary end points were amenorrhea, volume of menstrual blood loss, distress from bleeding and pelvic discomfort, anemia, pain, fibroid volume, and uterine volume. Safety and bone mineral density were assessed.ResultsA total of 388 women in trial L1 and 382 in trial L2 underwent randomization. A total of 73% of the participants in the relugolix combination therapy group in trial L1 and 71% of those in trial L2 had a response (primary end point), as compared with 19% and 15%, respectively, of those in the placebo groups (P<0.001 for both comparisons). Both relugolix combination therapy groups had significant improvements, as compared with the placebo groups, in six of seven key secondary end points, including measures of menstrual blood loss (including amenorrhea), pain, distress from bleeding and pelvic discomfort, anemia, and uterine volume, but not fibroid volume. The incidence of adverse events was similar with relugolix combination therapy and placebo. Bone mineral density was similar with relugolix combination therapy and placebo but decreased with relugolix monotherapy.ConclusionsOnce-daily relugolix combination therapy resulted in a significant reduction in menstrual bleeding, as compared with placebo, and preserved bone mineral density in women with uterine fibroids. (Funded by Myovant Sciences; LIBERTY 1 [L1] and LIBERTY 2 [L2] ClinicalTrials.gov numbers, NCT03049735 and NCT03103087, respectively.)

Platelet function disorder in women with heavy menstrual bleeding in Eastern Uttar Pradesh

Background: Platelet function disorder (PFD) is turning out to be a major cause of heavy menstrual bleeding (HMB) in women. One should suspect for this entity and should look for it in all girls who have this issue since menarche to impart proper management. Objectives: This study was carried out to find the incidence of PFD in Patients with HMB referred to our tertiary care teaching hospital. Materials and Methods: Platelet aggregation in response to ristocetin-induced platelet aggregation (RIPA), Adrenaline, adenosine diphosphate, and Collagen was studied in 50 women with HMB and in the equal number of age-matched healthy women. Bleeding time and Platelet count were also measured. Results: Glanzmann's thrombasthenia (GT) was detected in 5 and Bernard Soulier Syndrome (BSS) in 2 women with HMB. Macrothrombocytopenia was observed in BSS. RIPA was also significantly reduced in BSS but normal in GT. Coagulopathies should always be doubted in the presence of significant anemia. One should carry out the Platelet function studies when screening parameters like prothrombin time, partial thromboplastin time, von Willebrand factor , and factor VIII activity level are normal. Normal platelet count and morphology in addition suggest functional defects in platelets which can be detected by various aggregation studies, electron microscopy, flow cytometry, and thromboelastography. Conclusion: The clinicians treating women with HMB should be aware of PFD as an important etiology and the platelet function should be studied in all women with HMB in a phase-wise manner in order not to miss the diagnosis and also to make it more cost-effective.

Heavy menstrual bleeding in women with inherited bleeding disorders.

Heavy menstrual bleeding (HMB) is the commonest bleeding symptom among women with inherited bleeding disorders (IBD). Since HMB starts at the very onset of menarche and continues throughout the reproductive life, the health related quality of life of these women is affected and they are at an increased risk of developing iron-deficiency anemia. Because of the entrenched stigma and taboos, women and girls are often reluctant to discuss the problem of HMB within their families and do not seek medical advice. Increased awareness and multidisciplinary management approach for the management of these women are essential in ensuring an optimal outcome. It is important to take a careful history and undertake a thorough gynecological assessment to exclude other underlying/concomitant causes of HMB. Iron supplementation is essential. Strategies for decreasing menstrual blood flow are similar to those used for HMB in general with the addition of desmopressin and replacement therapy and the exclusion of non-steroidal anti-inflammatory drugs. Tranexamic acid and/or hormonal intervention are usually recommended as first-line therapy. Treatment choice should be individualized taking into account whether the woman wishes to preserve her fertility, if she requires contraception, the type of IBD, the severity of bleeding, and her social and religious background as well as acceptability and availability of the treatment options.

Women prefer proactive support from providers for treatment of heavy menstrual bleeding: A qualitative study in adult women with moderate or severe Von Willebrand disease.

To explore key factors for successful support in women with moderate or severe Von Willebrand disease (VWD) who are faced with heavy menstrual bleeding (HMB) and surgery. A qualitative study design with focus-group interviews and thematic analysis of the discussions. Eleven VWD women aged 41-68years (median age 58years) who had had a hysterectomy or bipolar radiofrequency ablation (BRA) because of HMB participated in this study. Three of the 11 participants had VWD diagnosed before surgery. Two focus groups were conducted in the summer of 2012. Patients were identified through participation in a nationwide study on Von Willebrand disease in the Netherlands (WiN study). Inclusion criteria were at least 18years of age, fluent in Dutch, diagnosed with VWD (based on Von Willebrand factor (VWF) antigen and/or activity levels < 30IU/dL) and previous surgical therapy for HMB. The following key factors were identified during focus-group interviews: receiving information, proactive support from providers and considering bleeding disorders as a cause of HMB. Other topics were as follows: experiences with VWD and/or surgery, how relieved patients were when menses stopped, patients hoped that in future, providers would work better together so that women receive the best care. In this focus-group study among women with VWD who underwent surgery because of HMB, support by professionals could be improved by considering a bleeding disorder in women with HMB, providing information about different types of surgery and shared decision-making regarding type of interventions.

Comprehensive Evaluation of Bleeding Disorders in Adolescents with Heavy Menstrual Bleeding

Introduction: Unpredictable, prolonged or heavy menstrual bleeding (HMB) is not unusual in many adolescents soon after menarche. Anovulation, owing to immaturity of the hypothalamic-pituitary-ovarian axis, is often the cause of HMB; however, it may coexist and mask an underlying bleeding disorder (BD). Retrospective data in adolescents with HMB suggest a prevalence of BDs from 10 to 62%. Prospective studies with uniform hemostatic evaluation and concurrent quality of life (QoL) assessments have not been performed. The incidence of BDs in adolescents, especially those with anovulatory bleeding, remains unknown. Methods: In this ongoing prospective cohort study (targeted n=200), 130 adolescents referred for HMB to multidisciplinary Young Women's Blood Disorders Clinics were enrolled. An assessment of menstrual loss using pictorial blood assessment chart (PBAC) and bleeding symptoms using ISTH-bleeding assessment tool (BAT) was undertaken. Participants underwent a comprehensive evaluation determined a priori, including assessment of hypermobility, standardized laboratory evaluation (prothrombin time, activated partial thromboplastin time, fibrinogen, thrombin time, von Willebrand disease (VWD) panel, whole blood platelet aggregation with ATP secretion, factor assays (FIX and FXIII), global hemostasis and hyperfibrinolysis using ROTEM, and a pelvic ultrasound (US). Patient reported outcomes for health related QoL(HR-QoL) was completed. Results: The mean age of participants was 14 (range 11-18) and mean age at menarche was 11.7 yrs. (range: 9-16). The mean PBAC score, before contraceptive initiation, was 504 (range: 100- 1200) and the mean ISTH BAT score was 3.8 (range: 1-8) in all participants. 62% had anovulatory menstrual bleeding. An inherited BD and/or bleeding risk was diagnosed in 24.6% (n=32); 9% (n=12) were diagnosed with VWD, 5% (n=6) with qualitative platelet dysfunction and 2 subjects were found to be hemophilia A (HA) carriers. Low VWF levels (VWF:Rco 30-50%) were detected in 9% (n=12). 15% had evidence of mild systemic hyperfibrinolysis (lysis 3-8% on ROTEM) but none met the criteria for further investigation for an inherited disorder of hyperfibrinolysis . Of those without BD, 2 were diagnosed to have VWF exon 28 polymorphism, and 3 were referred and ultimately diagnosed with hypermobility syndrome by Genetics. One was found to have endometriosis by laparoscopy and 3 were diagnosed with PCOS. Of those with BDs (all with low VWF), 3 were diagnosed with hypermobility syndrome (total 6) and 4 with PCOS (total 7). US was normal in all subjects. The PBAC scores were higher in BDs (634 vs. 410; SD ± 275 p=0.002), irrespective of the pattern of bleeding. No differences were found in the ISTH BAT scores (after excluding HA carriers) (3.6 vs. 4.8; SD ± 1.19, p=0.06), initial hbg or ferritin levels between the two groups. Only 6% (n=8) with BDs required ED visit and/or hospitalization for HMB vs. 14% (n=18) without a BD, of which majority had anovulatory bleeding. On multivariate logistic regression, no predictors of BDs were found. Adolescents with BDs had a decreased HR-QoL compared to those without a BD (QoL score 58 vs.87; SD± 12.5, p=&lt;0.001) even after control of HMB and correction of anemia. Conclusions: Inherited BDs are common in adolescents with HMB, confer a decreased HR-QoL and can be associated with anovulatory bleeding. A comprehensive evaluation is required to unravel disorders causing HMB. In this ongoing study, at this time, no predictor of an inherited BD was found in adolescents with HMB. Data accrual from the fully powered, ongoing, prospective study may offer further data to develop an ideal tool with a scoring system to take into account all prevalent causes of HMB to accurately predict a BD in adolescents. Disclosures Zia: NHLBI K23: Research Funding. Journeycake:CSL: Consultancy; Biogen: Consultancy; Baxalta/Shire: Consultancy. Jain:Novo Nordisk: Honoraria; Bayer: Membership on an entity's Board of Directors or advisory committees; Biogen: Speakers Bureau. Sarode:CSL Behring: Consultancy, Honoraria.

Prospective Evaluation of ISTH-BAT As a Predictor of Bleeding Disorder in Adolescent Girls with Heavy Menstrual Bleeding

Background. Heavy menstrual bleeding (HMB) is a frequent complaint in adolescence and is often multifactorial. Of the possible causes, anovulation is likely to be the most common reason but there is mounting evidence that bleeding disorders (BDs) are often an unidentified cause of HMB. Wide ranges of reported prevalence, difficulty in discerning normal from excessive menstrual bleeding and the semi-empiric use of hormonal therapy makes identifying BDs in adolescents challenging. Bleeding assessment tools (BATs) have been developed- primarily in the adults - to improve diagnostic accuracy, predict bleeding phenotype and describe symptoms. The International Society of Haemostasis and Thrombosis (ISTH) BAT was specifically designed to quantify bleeding symptoms that are pediatric specific. An ISTH-BAT score of &gt; 3 for children is considered abnormal. The ISTH BAT has not yet been specifically tested in adolescents presenting with HMB. The objective of this study was to examine the diagnostic utility of ISTH-BAT bleeding score (BS) of &gt; 3 as a predictor of BDs in adolescents with HMB. Methods. We prospectively analyzed clinical data on 70 adolescents without a known BD, referred for HMB, to the Adolescent, Gynecology and multidisciplinary Young Women's Blood Disorders Clinics at University of Texas Southwestern Medical Center from July 2014 to June 2016. This cohort is part of an ongoing prospective study investigating the incidence of BDs in adolescents with HMB (planned n=200). All subjects underwent a standardized comprehensive diagnostic approach, including the ISTH BAT to quantify bleeding symptoms accurately. The ISTH-BAT was applied by two trained investigators and any discrepancy in scores was settled by discussion. As per National Heart, Lung, and Blood Institute guidelines, VWF:Ag and/or VWF:RCo&lt;30 IU/dL were labeled "definite von Willebrand disease (VWD)" while 30-50 IU/dL were labeled as "low VWF levels" which were grouped together to represent vWD. Receiver operating characteristics (ROC) of ISTH-BAT were determined to assess its value for predicting BD in our cohort. Results. The mean age of study participants was 14.4+1.8 years (range: 11-18 years). Twenty-eight out of 70 patients (40%) were found to have a BD; 8 met criteria for VWD, 12 had low VWF levels, 2 were hemophilia A carriers, 5 were diagnosed with inherited platelet dysfunction and 1 had inherited thrombocytopenia. The mean BS was higher in subjects with VWD (N=20) as compared to those without a BD (N=42) (4.5 +1.6, vs. 3.6+ 1.0, p= 0.02). At least one other bleeding symptom was present in 8 (40%) of the 20 girls with vWD. The most commonly reported bleeding symptoms were epistaxis (35%), oral (15%), cutaneous (10%) and post-surgical (5%). There was no difference in patterns of menstrual bleeding (anovulatory vs. ovulatory) between girls with and without a BD (55% ovulatory vs. 41% ovulatory, p-=0.28). ROC analysis of the ISTH-BAT bleeding scores showed that at a BS of &gt; 3, the sensitivity of the ISTH BAT was 100% but specificity was only marginal at 2.4% with an accuracy of 41%, whereas at a BS of &gt; 5, sensitivity, specificity and accuracy were 30%, 88.10% and 69%, respectively. ROC analysis showed area under the curve of 0.66 (CI: 0.52-0.80) indicating poor discrimination for the ISTH-BAT score in determining BD in girls with HMB. Conclusion. Our study is the first attempt to prospectively examine the applicability of using ISTH-BAT score as a screening tool to exclude the presence of BD in adolescent girls presenting with HMB. In this study cohort, ISTH-BAT bleeding score of &gt; 3 demonstrated poor diagnostic accuracy in ruling out vWD. A score of &gt; 5 had high specificity which can decrease false positive diagnosis and repetitive testing. Future data from the ongoing study will help understand how a combination of BATs and a laboratory testing algorithm can unravel hemostatic defects in adolescents with HMB. Disclosures Jain: Bayer: Membership on an entity's Board of Directors or advisory committees; Biogen: Speakers Bureau; Novo Nordisk: Honoraria. Sarode:CSL Behring: Consultancy, Honoraria. Journeycake:CSL: Consultancy; Biogen: Consultancy; Baxalta/Shire: Consultancy. Zia:NHLBI K23: Research Funding.

Non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women with bleeding disorders.

Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common. This is an update of a previously published Cochrane Review. To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders. We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (25 August 2016), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013). Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder. Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias. Three cross-over studies, with 175 women were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.

Menstrual management and reproductive concerns in adolescent and young adult women with underlying hematologic or oncologic disease.

Heavy menstrual bleeding is common among adolescent and young adult women, and can affect health-related quality of life. The cause of heavy menstrual bleeding is not uncommonly because of an underlying hematologic or oncologic disease process, which substantially influences the way patients are counseled and treated. Options for menstrual management are more numerous today than ever before and range from minimizing monthly blood loss to suppressing the cycle altogether. However, an underlying bleeding disorder or malignancy can introduce many nuances and limits in individual patient care, which this review highlights. Additionally, because survival rates for adolescent and young adult cancers are improving, more of these patients are planning for lives after their disease, which may include starting or adding to a family. Options for fertility preservation during cancer therapy regimens are solidifying and both primary practitioners and subspecialists should be aware of the possibilities. Patients with underlying hematologic or oncologic disease require management of menstrual bleeding, but also deserve a comprehensive evaluation and counseling regarding their individualized contraceptive needs and fertility preservation options during their reproductive years. This review employs the latest evidence from current literature to help guide clinicians caring for this unique demographic.

Heavy menstrual bleeding

Heavy menstrual bleeding (HMB) is one of the most common reasons for primary care consultations by women of reproductive age. The condition is associated with a reduction in health-related quality of life and substantial utilisation of health service resources. There are several underlying causes of HMB, which are generally benign in nature and can exist in isolation or in combination. The majority of women presenting with HMB can be managed in primary care, either expectantly or using effective medical treatments. Referral to secondary care should be restricted to refractory cases, where surgical or radiological interventions may be indicated and where pre-malignant or malignant uterine disease is suspected. This article will explore the nature of HMB, the terminology that should be used to describe menstrual disorders and the aetiology of HMB. Diagnostic work-up and clinical management, encompassing treatment in primary care and indications for referral to secondary care based on national clinical guidance, will also be discussed.

Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding.

Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding.

Histopathology findings in patients presenting with menorrhagia: A study of 100 hysterectomy specimen.

Background:Menorrhagia, by definition, is heavy cyclical blood loss in excess of 80 ml/month of menstrual period lasting longer than 7 days. There are many possible causes of heavy menstrual bleeding which include hormonal imbalance, fibroids, miscarriage or ectopic pregnancy, nonhormonal intrauterine device, adenomyosis, pelvic inflammatory disease, and rarely uterine, ovarian, or cervical cancer. Treatment depends on the causes of the menorrhagia. Hysterectomy is one of the several surgical procedures as definitive treatment.Objective:To determine the histopathologic spectrum of lesions associated with menorrhagia in different age groups.Study Design:This prospective descriptive study was conducted at the Department of Pathology, People's College of Medical Sciences and Research Centre, Bhopal. During the study period, 100 hysterectomy specimens were taken which were performed for the treatment of menorrhagia. Patients with menorrhagia in the age group of 30-50 years were selected after detailed history and fulfilling the inclusion criteria.Result:In our study, it was observed that maximum number of cases were in the age group of 41-50 years (n = 35) followed by the age group of 31-40 (n = 30). Out of 100 cases, 31% cases (n = 31) showed adenomyosis followed by leiomyomas 25% (n = 25), endometrial hyperplasia 23% (n = 23), and endometrial polyp 4% (n = 4). 11% cases (n = 11) showed dual pathology consisting of both adenomyosis and endometrial hyperplasia and 6% cases (n = 6) of leiomyoma with adenomyosis.Conclusion:Uterine adenomyosis and leiomyoma are the most common benign conditions found in hysterectomy specimens with peak incidence at 31-50 years. Patients having menorrhagia above 40 years should be screened for any endometrial pathology. Histopathology is mandatory for confirming diagnosis and the key to effective therapy and optimal outcome.