Bleeding In Women Research Articles

Incidence and Impact on Quality of Life of Heavy Menstrual Bleeding in Women on Oral Anticoagulant Therapy.

Heavy menstrual bleeding affects up to two thirds of women on oral anticoagulation. The rates of heavy menstrual bleeding, its impact on quality of life and associated risk factors in women attending anticoagulation clinics in South Africa are largely unknown. A prospective cohort study was performed over an eight-month period in women on Warfarin (n = 30) and Rivaroxaban (n = 27) for a median [interquartile range] duration of 15.5 [78.0] months attending an anticoagulation clinic in Johannesburg, South Africa. Heavy menstrual bleeding was assessed over one menstrual cycle using the validated pictorial blood loss assessment charts (PBAC) and the menstrual bleeding questionnaire (MBQ). In this population of predominantly African ethnicity, with a median age of 39 [8] years, 39 (68.4%) women experienced heavy menstrual bleeding, defined as a PBAC score of >100. Median cycle length on anticoagulation and MBQ scores were significantly higher among women with a PBAC score of >100 (p > 0.05). Univariate analysis identified Rivaroxaban as a risk factor for heavy menstrual bleeding (OR 5.03, 95% CI 1.40-18.12). Heavy menstrual bleeding required treatment in 29 (74.4%) women which included management of iron deficiency, anti-fibrinolytics, modification of anticoagulation and hormonal contraception. Heavy menstrual bleeding was associated with a considerable negative impact on quality of life. This was most significant for women on Rivaroxaban as compared to Warfarin. It is essential to monitor and appropriately treat heavy menstrual bleeding in at risk women on anticoagulant treatment.

PB0205 High Prevalence of Heavy Menstrual Bleeding in Women with Rare Bleeding Disorders in the Netherlands: Retrospective Data from the RBiN Study

PB0205 High Prevalence of Heavy Menstrual Bleeding in Women with Rare Bleeding Disorders in the Netherlands: Retrospective Data from the RBiN Study

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.

Postmenopausal Bleeding in Women Utilizing Hormone Replacement Therapy: Not all the patients need to be referred or investigated

Postmenopausal Bleeding in Women Utilizing Hormone Replacement Therapy: Not all the patients need to be referred or investigated

Abnormal Uterine Bleeding in Women<40 Years and Its Risk Factors

Background: Abnormal uterine bleeding (AUB) is a common cause for outpatient and emergency department visits in reproductive-aged women and may have a significant impact on quality of life. Objective: The study aimed to determine the clinical risk factors for abnormal uterine bleeding in women <40 years age. Methods: This was a cross-sectional study conducted in the Obstetric & gynae department in Khwaja Yunus Ali medical college and hospital from January 2021 to December 2021. Clinical information was retrieved retrospectively from the patients' medical records. Results: 120 women of reproductive age with abnormal uterine bleeding participated in the study. Most of them were in the 36-40 age group. The patients' average age was 34.28 years. 88 (73.33%) had a large uterus, and 86 (70%) had atypical menstruation histories. Clinical symptoms included 35 (29.17%) heavy periods, 28 (23.33%) metrorrhagia, 22 (18.33%) polymenorrhea, 17 (14.17%) oligomenorrhea, 6 (5%) amenorrhea, and 12 (10%) reported symptoms of intermenstrual bleeding. After reviewing the medical records, it was discovered that 33 (27.5%) had diabetes, 37 (30.83%) had hypertension, 16 (13.33%) had both diabetes and hypertension, 7(5.63%) had hypothyroidism, 5 (4.17%) had cancer, 19(15.83%) were obese, and the majority of the patients, 87 (72.5%) were anemic. Multiple pregnancy was also a significant factors for AUB. Conclusion: AUB can be caused by factors such as increased age, obesity, nulliparity, irregular menstrual cycles, a history of diabetes, hypertension, and more. The only risk factor in the present study that was statistically significant was irregular menstruation history. Bulky uterus, multiple pregnancies, and irregular menstrual cycles may be related with abnormal uterine bleeding.

Clotting Factor Deficiencies as an Underlying Cause of Abnormal Uterine Bleeding in Women of Reproductive Age: A Literature Review.

Clotting Factor deficiencies are rare disorders with variations in clinical presentation and severity of symptoms ranging from asymptomatic to mild to life-threatening bleeding. Thus, they pose a diagnostic and therapeutic challenge, mainly for the primary health care providers, general practitioners, and gynecologists who are more likely to first encounter these patients. An additional diagnostic challenge arises from the variable laboratory presentations, as PT, PTT, and BT are not always affected. The morbidity is higher among women of reproductive age since Abnormal Uterine Bleeding-specifically Heavy Menstrual Bleeding-is one of the most prevalent manifestations of these disorders, and in some cases of severe deficiencies has led to life-threatening episodes of bleeding requiring blood transfusions or even immediate surgical intervention. Physician awareness is important as, in the case of some of these disorders-i.e., Factor XIII deficiency-prophylactic treatment is available and recommended. Although uncommon, the potential for rare bleeding disorders and for hemophilia carrier states should be considered in women with HMB, after more prevalent causes have been excluded. Currently, there is no consensus on the management of women in these instances and it is reliant on the physicians' knowledge.

Effectiveness of Persian Golnar on Excessive Menstrual Bleeding in Women with Abnormal Uterine Bleeding, Compared to Tranexamic Acid: A Triple-Blind, Randomized Equivalence Trial.

Abnormal uterine bleeding (AUB) is a major healthcare problem in females of reproductive age and impacts women's health and quality of life (QoL). This study aimed to test the equivalence of Persian Golnar (PG) and tranexamic acid (TA) for the treatment of excessive menstrual bleeding. A triple-blind randomized equivalence trial with parallel design and block randomization technique was performed. A total of 80 patients with AUB were randomly allocated to receive either PG or TA for three consecutive menstrual cycles. Blood loss was measured by the Pictorial Blood Loss Assessment Chart (PBAC). Hematological evaluations were done before the intervention and after treatment. QoL and premenstrual dysphoric disorder (PMDD) as secondary outcomes were assessed using the menorrhagia questionnaire (MQ) and Premenstrual Symptoms Screening Tool (PSST). Statistical analysis was performed using an independent t-test, paired t-test, χ2 test, Mann-Whitney test, and Wilcoxon signed-rank test. Seventy-six women completed the 12-week follow-up. Both PG and TA groups experienced a significant reduction in blood loss. Furthermore, the serum level of hemoglobin in the PG group enhanced significantly (P < 0.001). QoL and PMDD scores were significantly improved in both groups (P< 0.001). The findings of the current trial supposed that the Golnar product is as effective as tranexamic acid in controlling bleeding and enhancing the quality of life and premenstrual symptoms.

The Empower Study - Design of a Randomized Clinical Trial to Assess the Efficacy and Safety of a Plasma-Derived Von Willebrand Factor / Factor VIII Concentrate for Heavy Menstrual Bleeding in Women with Von Willebrand Disease

Background: Although von Willebrand disease (VWD) is inherited by men and women equally, women are more likely to experience bleeding symptoms due to the challenges of menstruation and childbirth. Heavy menstrual bleeding (HMB) is the most common symptom observed in women and girls with VWD, and increases risk of iron deficiency anemia, blood transfusion, hospitalization and decreased health-related quality of life. While replacement therapy with von Willebrand factor (VWF) is recommended for prophylaxis in patients with VWD with severe and frequent bleeding, recommendations on its use for prophylaxis of HMB are limited due the lack of clinical trial data. Aims: The EMPOWER pilot trial will determine the feasibility of the trial design, as well as explore assay sensitivity to inform the determination of the primary outcome for the definitive randomized trial which will evaluate the effect of prophylaxis with plasma-derived VWF/FVIII (1:1; pdVWF:FVIII) concentrate compared with placebo on HMB in women with VWD. Methods: EMPOWER is a pilot, randomized, placebo-controlled, crossover, double-blind (patient and outcome assessor blinded), 2-year trial in female outpatients with VWD and HMB. We will evaluate the effect of 2-3 doses of prophylaxis with 40-60 IU VWF:RCo/kg pdVWF/FVIII concentrate when provided on the 2 heaviest days within the first 4 days of menstruation compared with placebo (normal saline). For the first treatment period, participants will be randomized to receive either pdVWF/FVIII concentrate or placebo for 4 cycles, crossing over to the comparator treatment during the second treatment period (see Figure 1). Non-pregnant female patients, ≥18 years of age with a diagnosis of inherited VWD (any type) with HMB defined as a modified pictorial blood assessment chart (mPBAC) score >100, on stable treatment for HMB and iron-deficiency anemia will be eligible. Patients with diagnosis of another bleeding disorder or the presence of >2 risk factors for venous thromboembolism will be excluded. The pilot trial viability outcomes include blinding index scores and participant drop-out rates. Feasibility outcomes include data completeness and rate of enrolment. The proposed primary clinical efficacy outcome is the mPBAC score and the key secondary efficacy outcome is the need for rescue therapy (i.e. >2 days of oral tranexamic acid use, additional treatment with pdVWF:FVIII concentrate, additional hormonal therapy for HMB, urgent/emergent gynecological surgery for HMB, treatment with intravenous iron, red blood cell transfusion, or hospital admission for HMB). Other secondary outcomes include major bleeding, clinically relevant non-major bleeding, red blood cell transfusion, fatigue and quality of life scores. Given the uncertainty in this area of research and the relative comparable clinical importance of proposed clinical efficacy outcomes, we will evaluate assay sensitivity to determine the outcome that has the greatest chance of detecting a difference between treatment periods. Assay sensitivity is defined as the ability of a scale to distinguish an effective from a less effective intervention or placebo. Assay sensitivity along with the proportion of missing data per clinical efficacy outcome and sample size considerations will influence the choice of primary outcome for the definitive trial. Safety will be evaluated by monitoring for hypersensitivity reactions, thromboembolic events and VWF inhibitors. The pilot trial will recruit 20 participants from Hemophilia Treatment Centres in Canada over 2 years. Results: The pilot trial is aiming to launch by the fall 2022. If the pilot trial is deemed feasible and viable, we will subsequently conduct a definitive international randomized controlled trial. Conclusion: Data from the EMPOWER trial will fill an important knowledge gap to facilitate evidence-based management of HMB in women with VWD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Histopathological Evaluation of Abnormal Uterine Bleeding in Women of Reproductive and Perimenopausal Age Groups

Histopathological Evaluation of Abnormal Uterine Bleeding in Women of Reproductive and Perimenopausal Age Groups

“If I wasn't a girl”: Experiences of adolescent girls with heavy menstrual bleeding and inherited bleeding disorders

BackgroundHeavy menstrual bleeding (HMB) is a presenting symptom of an inherited bleeding disorder (BD) and results in hospitalizations, limitations of daily activities, and a reduction in quality of life. Adult women with BD report a sense of stigma, difficulties understanding their bleeding, and challenges with diagnostic labels. The experiences of adolescents with HMB and BD are unknown despite advances in medical management through the rapidly growing network of young women's hematology programs. ObjectivesThe objective of our qualitative study was to describe the experiences of adolescents with HMB with a BD and the impact on their day‐to‐day lives. Patients/MethodsOur qualitative study utilized semistructured interviews with adolescents with HMB after a BD diagnosis. We included adolescents with a BD within a multidisciplinary Young Women's Bleeding Disorders Clinic who had achieved menarche within the preceding 3 years and conducted interviews until theme saturation. All interviews were transcribed verbatim and analyzed using qualitative thematic descriptive analysis. ResultsWe identified the following themes in nine participants: anxiety and embarrassment, especially related to school; isolation and “otherness”; increased cautiousness and planning because of HMB and BD; and empowerment and identity formation because of the diagnosis of a BD. ConclusionsOur study uncovers previously unappreciated experiences of adolescents with HMB and a BD. HMB is an isolating and stressful experience in adolescents, but a BD diagnosis results in identity formation and empowerment. Psychological support and facilitating connections to others with similar life experiences soon after diagnosis represents key areas for targeted interventions.

Monitoring to improve quality of life in women with bleeding disorders

Abstract Systematic structures to understand the incidence and prevalence of bleeding disorders in women and girls are in place in some countries and becoming more robust, though there is still room for improvement. More co-ordinated data gathering is providing new insights into the diagnosis and treatment of girls with bleeding disorders and demonstrating clear deficits in care compared with boys that can have important implications around puberty. Recognition and recording of female symptoms such as heavy menstrual bleeding (HMB) may lag behind that of symptoms with a greater perception bias, such as joint bleeds, and affect quality of life and wellbeing. Addressing inequity of symptom recognition and recording is needed to drive appropriate and timely treatment interventions. New symptom tools can empower patients to differentiate normal from abnormal bleeding so they can seek and receive help. Greater awareness among health care professionals (HCPs) of women's bleeding disorders and the establishment of referral networks for diagnosis and treatment, with multidisciplinary assessment and follow-up, are still needed.

Bleeding Women in Sacred Spaces: Negotiating Theological Belonging in the ‘Pathway’ to Priesthood

This article focuses on the theological journeying of women ordinands in the Church of England, who have had to negotiate their belonging in the ‘pathway’ to Priesthood in ordination training. Attention is given to the extent to which the personhood of women is enabled to truly flourish in a theological education system that is dominated by men and predominantly patriarchal and Western theologising. It suggests that a gendered politics of belonging has been used and maintained through the socio-religious construct of ‘shame’ in order to maintain the boundaries of belonging within the formation process, and therefore calls for an en-gendered ‘pathway to the priesthood’. This is exemplified in a re-reading of the bleeding woman who dares to challenge the hegemonies of patriarchy and purity by touching the cloak of Christ in Luke 8:40-48. This research is part of an ongoing project with Common Awards at Durham University that explores barriers to belonging in theological education for those in training for ordination. It has therefore received ethical approval for interviews and participant observations.

The Association between Heavy Menstrual Bleeding and Depressive Symptoms in Adolescents

Introduction: Heavy menstrual bleeding (HMB) is a type of abnormal uterine bleeding (AUB) that affects 30% of women of reproductive age and up to 40% of adolescents. Furthermore, 10-40% of adolescents with HMB have an underlying inherited bleeding disorder like von Willebrand disease or platelet dysfunction, requiring management by pediatric hematologists. HMB has been described as more than 80 ml of blood loss during one cycle and clinically, it is defined by several parameters such as the length of each cycle, severity of soaking through pads or tampons, size of clots passed and pictorial blood loss assessment chart (PBAC) score. Studies in adult women show a significant impact of HMB on their psychosocial and financial health. However, little is known about the psychological effects of HMB in adolescent females. In the adolescent population, depression is twice as common in females as it is in males, likely due to a combination of biological and social differences. In this study, we examine the association between heavy menstrual bleeding and depressive symptoms in adolescent girls.Methods: We conducted a retrospective records review of adolescent females aged 10-21 years that were seen as new patients at the Adolescent Medicine and Young Women's Bleeding Disorders clinics at our institution between January 1, 2018 and March 31, 2020. Patients were included in the study if they had started menses, and had a doumented menstrual history as well as a completed Patient Health Questionnaire (PHQ-9), a validated screening tool for depression.Patients with a severe underlying chronic medical disorder (Including but not limited to end stage renal disease, Juvenile Rheumatoid Arthritis, Systemic Lupus Erythematosis, severe eating disorder, previously diagnosed bipolar disorder or psychotic disorders) were excluded. HMB was determined by either a PBAC score of >100 or the presence of two or more of the following criteria:Menses lasting >7daysSoaking through pad or tampon <1hrSoaking through bed clothes or changing pads at nightPassing large clotsLow ferritin < 15ng/ml (indicative of low iron stores)Anemia with Hemoglobin < 12g/dl not due to any other cause (e.g. dietary, immunosuppression, medication induced)Depression was determined by a PHQ-9 score of 9 or greater. The two variables were dichotomized, and a chi-square test of independence was performed to test the association with a significance level of p < 0.05.Results: A total of 203 records were reviewed after meeting inclusion and exclusion criteria. The mean age was 15.94 years (median 16, mode 16) with a range of 12-20years. 42 girls (20.7%) had a PHQ-9 score of >9 and 52 (25.6%) had HMB. Eighteen of the 42 patients (42.8%) with elevated PHQ-9 score had HMB and 34/52 patients (65.3%) with HMB had an elevated PHQ-9 score. Pearson's chi-square test of independence showed a significant relation between HMB and PHQ-9 score of 9 or more with χ 2 (1, n=203) = 8.2618, p = 0.004. After the application of Yates correction, the result was still significant with χ 2 = 7.1603 and p = 0.007.Discussion and Conclusions: This study shows a significant association in the adolescent population between heavy menstrual bleeding and moderate or severe depression as defined by the presence of a PHQ-9 score of 9 or more. This retrospective analysis does not establish causation, but demonstrates a clinically noteworthy finding that has not been described before. The PHQ-9 is used widely across this population to screen for depression, but it is also important to screen young women aged 10-21years for HMB as a contributing factor to depression followed by timely and appropriate management of both problems. Additionally, it may be worthwhile to evaluate all young women with HMB through additional methods to diagnose depression as this patient population appears to be at higher risk. Future prospective studies are needed to better characterize this association. DisclosuresNo relevant conflicts of interest to declare.

Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids.

Objective:To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2).Methods:Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events.Results:Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders.Conclusion:Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328–340) DOI: 10.1056/NEJMoa1904351

Oriahnn: New Drug Approved for Treating Heavy Menstrual Bleeding in Women With Uterine Fibroids.

To review data of elagolix plus estradiol and norethindrone acetate as add-back therapy for the treatment of heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids. Literature search of PubMed/MEDLINE and SCOPUS was performed using the search terms Oriahnn; elagolix, estradiol, norethindrone AND heavy menstrual bleeding; elagolix AND heavy menstrual bleeding; and gonadotropin-releasing hormone receptor antagonist AND heavy menstrual bleeding between January 1, 1996, to March 2, 2021. Additional data were obtained from prescribing information, references of identified articles, and abstracts from scientific meetings. Clinical trials and articles discussing elagolix plus add-back therapy for the management of HMB in women with leiomyomas were included. Phase 3 trials met the primary end point of menstrual blood loss (MBL) less than 80 mL at month 6 and at least a 50% reduction in MBL from baseline to the final month in 68.5% of women taking elagolix plus add-back therapy enrolled in UF-1 (8.7% placebo) and 76.5% of women in UF-2 (10% placebo). The most common adverse effects include hot flushes, nausea, headache, and night sweats. Women with symptomatic uterine fibroids can experience significant HMB resulting in distress, depression, and anxiety. Surgical intervention remains the most commonly recommended and chosen treatment. Elagolix plus add-back therapy is a nonsurgical, oral option. Elagolix plus add-back therapy is effective in reducing menstrual bleeding associated with uterine fibroids. However, there are several warnings and precautions that must be considered.

Energies Alterations and Chakras’ Energies Deficiencies as One Cause of Abnormal Uterine Bleeding in Women

Energies Alterations and Chakras’ Energies Deficiencies as One Cause of Abnormal Uterine Bleeding in Women

Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids

BackgroundUterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding.MethodsWe conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal “add-back” therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation.ResultsA total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.ConclusionsElagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.)

Abstract 232: Effect of Oral Anticoagulation Use on Thromboembolic Risk and Bleeding in Women Compared with Men with Atrial Fibrillation: Findings from the PINNACLE Data Registry

Background: Among those with atrial fibrillation (AF), women have a higher risk of thromboembolic events and lower use of oral anticoagulation (OAC) when compared to men. Whether the effect of gender on thromboembolic risk in patients with AF is mediated by lower use of OAC among women is unknown. We examined whether gender differences in OAC use mediated the relationship between gender and thromboembolic risk in patients with AF. Methods: Adults 65 years and older with AF in the PINNACLE Registry from October 2008 to December 2014 were identified. Adults with valvular AF and contraindications to OAC use were excluded. Thromboembolic events (stroke, systemic embolism) and major bleeding events were determined using linked Medicare claims data. Site-stratified proportional hazard models adjusting for patient and practice-level characteristics compared thromboembolic and bleeding events by gender, as well as the mediating effect of OAC use as a time-dependent covariate on these outcomes. Results: Among 667,287 patients, the mean ±standard deviation age was 77±8 years and 46% were women. Compared to men, women had higher CHA2DS2-Vasc scores (mean 4.8 vs. 3.8, p&lt;0.001), had similar prevalence of bleeding risk factors, but were prescribed OAC less frequently (51.5% vs. 53.8%, p&lt;0.001). Over a median 2 years of follow up (range 0-6 years), there were 25,947 thromboembolic events and 40,967 major bleeding events. Women had a higher risk of thromboembolic events compared to men (5-year cumulative incidence 8.3% vs. 6.0%, adjusted hazard ratio [HR] 1.24, 95% CI 1.16-1.33) and a slightly lower risk of major bleeding (5-year cumulative incidence 10.4% vs. 11.2%, adjusted HR 0.90, 95% CI 0.83-0.98). Among adult patients with AF, OAC use was associated with lower thromboembolic risk (HR 0.90, 95% CI 0.86-0.94) and greater bleeding risk (HR 1.51, 95% CI 1.42-1.60). Among women, OAC use did not mediate the relationship between gender and either thromboembolic or major bleeding events (HR 1.24 and 0.90 respectively, identical to the unmediated effects). Conclusions: In a national US sample of older adults with AF, women had lower rates of OAC use, higher risk of thromboembolic events and lower risk of major bleeding. However, the difference in OAC use did not explain the gender differences in these outcomes. These findings underscore that women with AF are independently at higher risk for thromboembolic events and lower OAC use among women does not significantly explain this higher risk.

PEMAHAMAN MAHASISWA FAKULTAS SYARI'AH DAN HUKUM UIN SUNAN AMPEL TENTANG FIQH PEREMPUAN

Understanding of women's fiqh associated with female bleeding (dima' al-mar'ah) is very important to be owned by men especially by women. Syari'ah and Law Faculty’s students are required to understand Shari'ah and law knowledge, one of which is about women's bleeding. However, in the curriculum of study programs in the Faculty of Shari'ah and Law of UINSA no one specifically discussed the matter. Understanding of students related to menstrual blood, childbirth and istihadhah majority is still at the moderate level. They can only define and know the difference in time when the blood comes out. As for the wisdom and legal implications for women who experience bleeding in the implementation of worship, they still do not know and define it. The implications of legal law that they know are only limited to prayer, fasting and carrying, holding and reading the Qur'an. The rest they are still confused or do not know. Of the several factors that influence a person's understanding, there are five main factors that greatly influence students' understanding regarding menstrual blood, childbirth and istihadhah, namely factors of experience, intelligence, gender, education and school environment. Other factors that are age, occupation, socio-culture and economy, and the amount of media information does not affect the students' understanding regarding menstrual blood, childbirth and istihadhah.

Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis

(Abstracted from JAMA Intern Med 2018;178:1210–1222) The incidence of endometrial cancer and deaths from this cancer has increased in recent years and is projected to rise over the next decade.