Association of heavy menstrual bleeding with cardiovascular disease in US female hospitalizations.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common menstrual disorder associated with multiple risk factors of cardiovascular disease (CVD) in women. In addition, HMB is often present with irregular menstruation (IM) which is a risk factor for CVD outcomes. However, the relationship between HMB and CVD outcomes is unexplored in the presence or absence of IM. We determined the association of HMB with multiple CVD outcomes using a nationally representative sample of female hospitalizations in the US. METHODS: All hospitalizations of females with HMB diagnosis and normal menstrual cycles from ages of 18 to 70 years were extracted from the National Inpatient Sample Database, 2017. The HMB was defined using the International Classification of Diseases (ICD)-10 for excessive and frequent menstruation bleeding and included any current or history of HMB diagnosis. Outcomes including major adverse cardiovascular events (MACE), coronary heart disease (CHD), stroke, heart failure (HF), atrial fibrillation (AF) or arrhythmia, myocardial infarction (MI), and diabetes (DM) were defined using ICD-10 codes. Adjusted logistic regression and prosperity scores-matched logistic regression analyses were conducted to summarize adjusted associations with an odds ratio (OR) and a 95% confidence interval (CI). RESULTS: Among 2,430,851 hospitalizations, HMB was observed in 7762 (0.68%) females with age ≤ 40 years and 11,164 (0.86%) females with age > 40 years. Among hospitalizations with age ≤ 40 years, HMB was significantly associated with increased odds of CVD outcomes including MACE (OR = 1.61; 95% CI: 1.25, 2.08), CHD (OR = 1.72; 95% CI: 1.10, 2.71), stroke (OR = 1.95; 95% CI: 1.12, 3.40), HF (OR = 1.53; 95% CI: 1.15, 2.03), and AF/arrhythmia (OR = 1.84; 95% CI: 1.34, 2.54). These associations were confirmed in multiple sensitivity analyses. In contrast, HMB was not robustly associated with CVD events among hospitalizations of women with age > 40 years. HMB without IM was strongly associated with DM, HF, AF, and MACE outcomes while HMB with IM was strongly associated with CHD and AF outcomes in hospitalizations of young women. CONCLUSIONS: HMB is associated with CVD events among US hospitalizations of young women. A routine investigation and screening of menstrual disorders, especially HMB, is useful for CVD risk stratification and management in young women.

Risk of Iron Deficiency in Women With Endometriosis: A Population-Based Prospective Cohort Study.

BACKGROUND: Endometriosis may be linked to the risk of iron deficiency through chronic systemic inflammation or heavy menstrual bleeding. No longitudinal studies, however, have examined the relationship between endometriosis and the risk of iron deficiency. METHODS: This study included 3,294 participants born from 1973 to 1978 and followed as part of the Australian Longitudinal Study on Women's Health from 2000 to 2018. Participants with endometriosis were identified using self-reported longitudinal surveys linked to administrative health records. During each survey, participants were also asked to report the diagnosis of iron deficiency, and we validated diagnoses using an administrative health database. Generalized estimating equations for binary responses with an autoregressive correlation matrix were used to examine the association between endometriosis and the risk of iron deficiency over the seven time points. FINDINGS: We found that women with endometriosis had a significantly higher risk of iron deficiency than those without endometriosis after adjusting for sociodemographic, lifestyle, reproductive, and nutrition factors (adjusted odds ratio [aOR] = 1.46; 95% confidence interval [CI] [1.29, 1.66]; p < .0001). Women with a surgically confirmed diagnosis and those with clinically suspected endometriosis had a higher risk of iron deficiency (aOR = 1.38; 95% CI [1.17, 1.64] and aOR = 1.53; 95% CI [1.30, 1.81]), respectively. These associations, however, were slightly attenuated (by 8%) when adjusted for the presence of heavy menstrual bleeding. CONCLUSIONS: Women with endometriosis are at a higher risk of developing iron deficiency than those without endometriosis. The findings suggest that iron deficiency should be concomitantly addressed during initial diagnosis and successive management of endometriosis.

Adenomyosis diagnosis among adolescents and young women with dysmenorrhoea and heavy menstrual bleeding.

RESEARCH QUESTION: What is the prevalence of adenomyosis at ultrasonography among adolescents and young women reporting dysmenorrhoea and/or heavy menstrual bleeding (HMB)? DESIGN: This observational cohort study involved adolescents and young women referred for dysmenorrhoea and/or HMB to the Adolescent Medicine Unit at Careggi University Hospital, Italy. Patients with endometriosis and bleeding disorders were excluded. Transvaginal ultrasonography or transrectal sonography using a transvaginal probe was performed. The myometrium was described according to the Morphological Uterus Sonographic Assessment criteria. Details of baseline characteristics, clinical data and symptoms were collected. The presence of sonographic features of adenomyosis and the association between imaging findings and clinical symptoms were evaluated. RESULTS: The cohort included 95 patients aged between 13 and 25 years, referred for dysmenorrhoea (88.4%), HMB (23.2%) or both (13.7%). According to the MUSA criteria the sonographic diagnosis of adenomyosis was made in 27.4% of patients, with the diffuse type the most prevalent. Uterine wall asymmetry, hyperechoic intramyometrial islands, translesional vascularity and an interrupted junctional zone were the most common features. Patients with imaging findings of adenomyosis had significantly higher rates of HMB than those with a normal myometrial appearance (38.5% versus 17.4%, P = 0.030). In addition, the coexistence of dysmenorrhoea and HMB was significantly associated with adenomyosis (odds ratio 5.68, 95% confidence interval 1.65-19.5). CONCLUSIONS: Adenomyosis may be diagnosed among teenagers and young women referred with dysmenorrhoea and/or HMB. The clinical presentation is relevant for the diagnosis, with HMB alone and HMB plus dysmenorrhoea significantly associated with the sonographic identification of adenomyosis.

Prevalence of heavy menstrual bleeding and associations with physical health and wellbeing in low-income and middle-income countries: a multinational cross-sectional study.

BACKGROUND: Data on the prevalence of heavy menstrual bleeding in low-income and middle-income countries (LMICs) are scarce. We aimed to assess the validity of a scale to measure heavy menstrual bleeding and calculate its prevalence in southern Asia and sub-Saharan Africa, and to examine associations between heavy menstrual bleeding and health outcomes. METHODS: Between Aug 2, 2021 and June 14, 2022, we surveyed 6626 women across ten cities (Meherpur and Saidpur, Bangladesh; Warangal, Narsapur, and Tiruchirappalli, India; Kathmandu, Nepal; Dakar, Senegal; Nairobi, Kenya; Kampala, Uganda; and Lusaka, Zambia), including questions on demographics, health, and the SAMANTA scale, a six-item measure of heavy menstrual bleeding. We conducted confirmatory factor analysis to assess construct validity of the SAMANTA scale, calculated the prevalence of heavy menstrual bleeding, and used regression analyses to examine associations of heavy menstrual bleeding with health outcomes. FINDINGS: 4828 women were included in the final analytic sample. Factor analysis indicated a one-factor model representing heavy menstrual bleeding. In the pooled analytic sample, 2344 (48·6%) of 4828 women were classified as experiencing heavy menstrual bleeding, and the prevalence was lowest in Dakar (126 [38·3%] of 329 women) and Kampala (158 [38·4%] of 411 women) and highest in Kathmandu (326 [77·6%] of 420 women). Experiencing heavy menstrual bleeding was significantly associated with feeling tired or short of breath during the menstrual period (risk ratio 4·12 (95% CI 3·45 to 4·94) and reporting worse self-rated physical health (adjusted odds ratio 1·27, 95% CI 1·08 to 1·51), but was not associated with subjective wellbeing (ß -3·34, 95% CI -7·04 to 0·37). INTERPRETATION: Heavy menstrual bleeding is highly prevalent and adversely impacts quality of life in women across LMIC settings. Further attention is urgently needed to understand determinants and identify and implement solutions to this problem. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, National Institutes of Health.

Comprehensive Analysis of Iron Deficiency Anemia and Its Related Disorders in Premenopausal Women Based on a Propensity Score Matching Case Control Study Using National Health Insurance Service Database in Korea.

BACKGROUND: Menorrhagia is a common cause of iron deficiency anemia (IDA) in premenopausal women. However, the effects of menorrhagia on IDA in premenopausal women have been underestimated compared to those on other IDA-related disorders (IRDs) such as gastrointestinal malignancies (GIMs). To better understand the relationship between menorrhagia and IDA in premenopausal women, we analyzed the National Health Insurance Service-National Health Information Database (NHIS-NHID). METHODS: From 2005 to 2008, data about women between the age of 20 and 59 years were extracted from the NHIS-NHID to create a propensity score-matched case (IDA) and control group. The annual incidence of IDA was calculated per age group. A 10-year follow up of the study population was determined to detect IRDs in case and control groups. We compared the risk of detection (ROD) of IRDs, including GIM and gynecological disorders associated with menorrhagia - leiomyoma of uterus (LM) and adenomyosis (AM), in the case and the control group. RESULTS: From 2005 to 2008, women diagnosed with IDA (n = 535,249) and healthy women as a control group (n = 1,070,498) were identified from the NHIS-NHID. The annual incidence of IDA was 767.4 (2005), 948.7 (2006), 981.6 (2007), and 897.7 (2008) per 100,000 women. The age distribution of IDA was similar each year; IDA was common in women aged 30-39 years (36-37%) and 40-49 years (30-32%), and its incidence was significantly decreased in women aged 50-59 years (< 10%). The ROD of IRDs were significantly higher in the IDA group than in the control group (LM: 20.8% vs. 6.9%, AM: 5.6% vs. 1.6%, and GIM: 2.6% vs. 0.7%). The corresponding hazard ratios were 3.89 (95% confidence interval [CI], 3.85-3.93) for LM, 4.99 (95% CI, 4.90-5.09) for AM, and 3.43 (95% CI, 3.32-3.55) for GIM. The ROD of the IRDs varied; the ROD of LM in the IDA group increased with age and decreased in the age group 50-59 years. AM was more frequently detected in women with IDA aged 30-39 years and less in women older than 40 years. The frequency of GIM increased with age. CONCLUSION: In this study, we found that the gynecologic disease is the main cause of IDA in premenopausal women. Gynecological evaluations should be performed more actively in the clinic to prevent and control IDA and IRDs.

Reflections on access to care for heavy menstrual bleeding: Past, present, and in times of the COVID-19 pandemic.

The symptom of heavy menstrual bleeding (HMB) affects at least a quarter of reproductive-age menstruators. However, given the variance in diagnosing the underlying causes, barriers, and inequity in access to care for HMB, and therefore reporting of HMB, this figure is likely to be a gross underestimate. HMB can have a detrimental impact on quality of life. From the limited reports available it is estimated that around 50%-80% of people with HMB do not seek care for this debilitating symptom, and for those that do, it may take years until the first treatment action. Almost half of those with HMB believe their condition is unworthy of treatment, that there is no treatment available, or that it is "normal". The term "medical gaslighting" has recently been used to describe how healthcare professionals disregard people's symptoms. This has the ensuing effect of negatively compounding self-doubt and embarrassment around menstrual bleeding, creating a cycle of diminished experience inhibiting further seeking of care. There is a scarcity of intervention studies informing increased access to care. Multilevel approaches are needed to increase access to care and support for those with HMB. During the COVID-19 global pandemic, barriers to care access and support for HMB have been exacerbated and, given the significant pressures that this pandemic has placed on healthcare services worldwide, it will take many years to recover. In the meantime, it is crucial to ensure that medically "benign" conditions such as the symptom of HMB are not overlooked.

Evaluation of Radiofrequency Endometrial Ablation: A 17-year Canadian Experience.

STUDY OBJECTIVE: The purpose of this study was to better elucidate radiofrequency endometrial ablation (REA) durability by assessing the probability of failure as defined by need for postablation hysterectomy. Age at index REA, duration from REA until hysterectomy, and REA failure (REAF) risk factors were analyzed. DESIGN: A retrospective cohort study was conducted using patient data between April 1, 2002, and March 31, 2019. REAF cases were identified using operative procedure codes. Cox proportional hazard regression assessed the effect of age at index REA on time to postablation hysterectomy. Kaplan-Meier survival curve evaluated timing of postablation hysterectomy, stratified by age at index REA. SETTING: This study was conducted at Regina General Hospital in Regina, Saskatchewan, Canada. PATIENTS: Patient population included those who were 21 years of age or older, were premenopausal, and had a history of heavy menstrual bleeding at the time of REA. INTERVENTIONS: The intervention under investigation was REA. MEASUREMENTS AND MAIN RESULTS: The overall probability of postablation hysterectomy was 22.6%. The probabilities of postablation hysterectomy were 36.1% for women younger than 30 years (n = 128), 28% for women 30 to 34.9 years old (n = 528), 29.6% for women 35 to 39.9 years old (n = 1152), and 17.6% for women 40 years and older (n = 2221). Characteristics associated with REAF included tubal occlusion, cesarean section, dysmenorrhea, and chronic pelvic pain (p <.01) among women younger than 40 years. Leiomyomas accounted for higher failure rates in women 40 years and older (p <.01). CONCLUSION: Postablation hysterectomy is more likely to occur in women younger than 40 years. REA can be considered in women aged 30 to 39.9 years old, who have no known REAF risk factors. Women younger than 40 years with REAF risk factors will experience higher rates of hysterectomy. Thus, the decision to proceed with REA should be individualized with careful consideration for the underlying causes of abnormal uterine bleeding, while respecting patient autonomy.

High prevalence of heavy menstrual bleeding in women with rare bleeding disorders in the Netherlands: retrospective data from the RBiN study.

BACKGROUND: Heavy menstrual bleeding (HMB) is associated with a reduced quality of life and limitations in social and physical functioning. Data on HMB in women with rare bleeding disorders (RBDs), including coagulation factor deficiencies and fibrinolytic disorders, are scarce. OBJECTIVES: To analyze the prevalence, severity, and treatment of HMB in Dutch women with an RBD. METHODS: The Rare Bleeding Disorders in the Netherlands (RBiN) study included 263 patients with an RBD from all 6 hemophilia treatment centers (October 2017-November 2019). In this analysis, data of 111 women aged ≥16 years were studied. According to the International Society on Thrombosis and Haemostasis bleeding assessment tool, HMB symptoms were scored from 0 (no/trivial) to 4 (severe symptoms requiring medical intervention). HMB was defined as a score ≥1. Age at RBD diagnosis was extracted from patient files. RESULTS: HMB was reported by 80% of women (89/111) and was more prevalent in women with a fibrinolytic disorder (33/35; 94%) than in women with a coagulation factor deficiency (56/76; 74%) (P = .011). Of the 89 women with HMB, 82% (n = 73) ever required treatment. Multiple treatment modalities were frequently used, both in severe and mild deficiencies. Hormonal treatment was mostly used (n = 64; 88%), while antifibrinolytics were prescribed less frequently (n = 18; 25%). In women with HMB since menarche (n = 61; 69%), median age at RBD diagnosis was 28 years (IQR, 14-41). CONCLUSION: HMB is common in women with RBDs. Women with mild deficiencies also frequently reported HMB. Only a minority of women were treated with hemostatic agents. A significant diagnostic delay was observed after the onset of HMB symptoms.

COVID-19 vaccination and menstrual disorders among women: Findings from a meta-analysis study.

BACKGROUND: COVID - 19 vaccine can lead to various local and systemic side effects, including menstrual irregularities in women. There is no robust quantitative evidence of the association between the COVID - 19 vaccine and menstrual irregularities. A meta-analysis was performed to estimate the pooled prevalence of a range of menstrual disorders that may occur in women following COVID - 19 vaccination. METHODS: After searching for epidemiological studies, we systematically performed a meta-analysis on PubMed/Medline, EMBASE, and Science Direct. Sixteen studies were finally included in the study. We estimated the pooled prevalence and corresponding 95 % confidence intervals (CIs) for a group of menstrual disorders, including menorrhagia, polymenorrhea, abnormal cycle length, and oligomenorrhea. Heterogeneity was assessed using the I2 statistic and the Q test. RESULTS: Overall, the pooled prevalence of menorrhagia was 24.24 % (pooled prevalence 24.24 %; 95 % CI: 12.8-35.6 %). The pooled prevalence of polymenorrhea was 16.2 % (pooled prevalence: 16.2 %; 95 % CI: 10.7-21.6 %). The pooled prevalence of abnormal cycle length was relatively lower than that of the other disorders (pooled prevalence: 6.6 %; 95 % CI: 5.0-8.2 %). The pooled prevalence of oligomenorrhea was 22.7 % (95 % CI: 13.5-32.0 %). CONCLUSION: The findings indicate that menorrhagia, oligomenorrhea, and polymenorrhea were the most common menstrual irregularities after vaccination. The findings also suggest that a relatively high proportion of women suffer from menstrual irregularities. Further longitudinal studies are needed to confirm the causal relationship between COVID-19 vaccination and menstrual irregularities.

Development of a brief menstrual quality of life measure for women with heavy menstrual bleeding.

BACKGROUND: The National Institute for Health and Care Excellence advises that considerations around quality of life should be made when assessing and treating heavy menstrual bleeding. A quick and reliable method for women to assess the impact of HMB on their quality of life might encourage help-seeking. This research aimed to develop a new 10-item measure of menstrual quality of life (the PERIOD-QOL). METHODS: Three pilot studies describe PERIOD-QOL development and a cross-sectional survey (N = 376) assessed PERIOD-QOL scores in women who reported HMB and those who did not. A population sample of women (mean age 30.29, SD = 9.06) completed the PERIOD-QOL and rated their menstrual bleeding as heavy/very heavy/extremely heavy (HMB group) or very light/light/moderate bleeding (LMMB) group. Data were analysed using independent samples Analysis of Variance and independent samples t-tests. RESULTS: Cronbach's Alpha for the PERIOD-QOL = .88. A significant reduction in PERIOD-QOL scores was found across the 6 levels of bleeding from very light to extremely heavy, and significantly lower PERIOD-QOL scores were reported in the HMB than the LMMB group. CONCLUSION: The results suggest that the PERIOD-QOL is a reliable measure and that women experiencing HMB reported significantly lower menstrual quality of life than those who did not. Further validation of the PERIOD-QOL is required to determine its relationships with existing measures of menstrual quality of life and to establish whether PERIOD-QOL scores are associated with decisions to seek help from health professionals and with verified diagnoses of conditions that cause HMB.

Treatment Patterns in Patients with Uterine Fibroids With and Without a Diagnosis of Heavy Menstrual Bleeding: Results from a Large U.S. Claims Database.

Background: This retrospective database analysis describes clinical characteristics and treatment patterns of U.S. women with a diagnosis for uterine fibroids (UF), both with and without heavy menstrual bleeding (HMB). Materials and Methods: Two cohorts aged 18-50 years with an incident UF diagnosis, comprising women with and without claims for HMB (UF-HMB and UF-only), were identified from the IQVIA PharMetrics® Plus database (January 1, 2010-December 31, 2019). The index date was the first UF claim following diagnosis; treatment patterns were documented for postindex years 1 and 2 and the full duration of postindex follow-up. Also identified were claims for symptoms or signs potentially associated with UF. Outcomes were the proportion of patients treated with pharmacologic therapies of interest and gynecologic procedures. Logistic regression was used to identify factors associated with postdiagnosis hysterectomy and hormonal therapy. Results: A total of 66,313 (71.8%) women were included in the UF-HMB cohort (mean age [standard deviation]) 42.6 [5.4] years), and 26,068 (28.2%) in the UF-only cohort (41.8 [6.3]). Median follow-up was ∼4 years. Pain was the most common symptom (42.7% in patients with UF-HMB and 36.6% with UF-only); also common were abnormal bleeding (15.6%, 11.5%) and fatigue (22.2%, 15.5%). Within 1 year of UF diagnosis, 28.8% and 49.2% of women with UF-HMB and UF-only, respectively, had no claims for relevant pharmacologic or surgical treatment. In logistic regression, multiple factors were associated with a higher likelihood of receiving hysterectomy or hormonal therapy. Conclusions: Patients with UF-HMB were more likely to receive UF treatment, either surgical or pharmacologic, than women with UF-only. Apart from HMB, pain was the most commonly documented symptom of UF.

Abnormal uterine bleeding patterns determined through menstrual tracking among participants in the Apple Women's Health Study.

BACKGROUND: Use of menstrual tracking data to understand abnormal bleeding patterns has been limited because of lack of incorporation of key demographic and health characteristics and confirmation of menstrual tracking accuracy. OBJECTIVE: This study aimed to identify abnormal uterine bleeding patterns and their prevalence and confirm existing and expected associations between abnormal uterine bleeding patterns, demographics, and medical conditions. STUDY DESIGN: Apple Women's Health Study participants from November 2019 through July 2021 who contributed menstrual tracking data and did not report pregnancy, lactation, use of hormones, or menopause were included in the analysis. Four abnormal uterine bleeding patterns were evaluated: irregular menses, infrequent menses, prolonged menses, and irregular intermenstrual bleeding (spotting). Monthly tracking confirmation using survey responses was used to exclude inaccurate or incomplete digital records. We investigated the prevalence of abnormal uterine bleeding stratified by demographic characteristics and used logistic regression to evaluate the relationship of abnormal uterine bleeding to a number of self-reported medical conditions. RESULTS: There were 18,875 participants who met inclusion criteria, with a mean age of 33 (standard deviation, 8.2) years, mean body mass index of 29.3 (standard deviation, 8.0), and with 68.9% (95% confidence interval, 68.2-69.5) identifying as White, non-Hispanic. Abnormal uterine bleeding was found in 16.4% of participants (n=3103; 95% confidence interval, 15.9-17.0) after accurate tracking was confirmed; 2.9% had irregular menses (95% confidence interval, 2.7-3.1), 8.4% had infrequent menses (95% confidence interval, 8.0-8.8), 2.3% had prolonged menses (95% confidence interval, 2.1-2.5), and 6.1% had spotting (95% confidence interval, 5.7-6.4). Black participants had 33% higher prevalence (prevalence ratio, 1.33; 95% confidence interval, 1.09-1.61) of infrequent menses compared with White, non-Hispanic participants after controlling for age and body mass index. The prevalence of infrequent menses was increased in class 1, 2, and 3 obesity (class 1: body mass index, 30-34.9; prevalence ratio, 1.31; 95% confidence interval, 1.13-1.52; class 2: body mass index, 35-39.9; prevalence ratio, 1.25; 95% confidence interval, 1.05-1.49; class 3: body mass index, >40; prevalence ratio, 1.51; 95% confidence interval, 1.21-1.88) after controlling for age and race/ethnicity. Those with class 3 obesity had 18% higher prevalence of abnormal uterine bleeding compared with healthy-weight participants (prevalence ratio, 1.18; 95% confidence interval, 1.02-1.38). Participants with polycystic ovary syndrome had 19% higher prevalence of abnormal uterine bleeding compared with participants without this condition (prevalence ratio, 1.19; 95% confidence interval, 1.08-1.31). Participants with hyperthyroidism (prevalence ratio, 1.34; 95% confidence interval, 1.13-1.59) and hypothyroidism (prevalence ratio, 1.17; 95% confidence interval, 1.05-1.31) had a higher prevalence of abnormal uterine bleeding, as did those reporting endometriosis (prevalence ratio, 1.28; 95% confidence interval, 1.12-1.45), cervical dysplasia (prevalence ratio, 1.20; 95% confidence interval, 1.03-1.39), and fibroids (prevalence ratio, 1.14; 95% confidence interval, 1.00-1.30). CONCLUSION: In this cohort, abnormal uterine bleeding was present in 16.4% of those with confirmed menstrual tracking. Black or obese participants had increased prevalence of abnormal uterine bleeding. Participants reporting conditions such as polycystic ovary syndrome, thyroid disease, endometriosis, and cervical dysplasia had a higher prevalence of abnormal uterine bleeding.

Iron deficiency anemia: Impact on women's reproductive health.

Iron deficiency (ID) and iron deficiency anemia (IDA) are highly prevalent among women across their life span, especially during the reproductive age. An iron-deficient state has been associated with a number of adverse health consequences, affecting all aspects of the physical and emotional well-being of women. Heavy menstrual bleeding, pregnancy state, and the postpartum period are the major causes of ID/IDA. However, despite the high prevalence and the impact on quality of life, ID/IDA among fertile age women remains underdiagnosed and undertreated. The present Views and Reviews provides an overview on IDA in women's health, describing the background on iron metabolism, heavy menstrual bleeding pathogenetic mechanisms, including a focus on uterine disorders, such as uterine fibroids and adenomyosis. Iron replacement therapies, patient blood management, and treatment options for uterine disorders also are explored.

From menarche to menopause, heavy menstrual bleeding is the underrated compass in reproductive health.

Menstruation is defined as monthly uterine bleeding, regarded as a sign of reproductive health. When characterized by excessive bleeding (heavy menstrual bleeding [HMB]), it may act as a useful clinical marker for diagnosis of reproductive diseases. Endometrial and myometrial mechanisms underlying abnormal uterine bleeding (AUB), which includes HMB, have hormonal, cellular, and molecular aspects. Structural and nonstructural causes of AUB, presenting with HMB as the major symptom, result in iron depletion and consequent anemia. Heavy menstrual bleeding can be considered as a single entity to identify the possible underlying causes, which may be different to some extent to those of AUB, as a whole. Furthermore, the difficulties in defining HMB through objective methods do not allow the current epidemiological scenario on the prevalence of the symptom among reproductive-age women to be outlined. Moreover, the introduction of new diagnostic methods, including imaging technologies, entails a revision of the available figures on HMB in different age groups from menarche to menopause. In addition, a proper diagnostic algorithm for HMB should be implemented to adapt recommendations for clinical investigation when HMB is present.

Impact of von Willebrand Disease on Women's Health Outcomes: A Matched Cohort Database Study.

Objective: To understand the impact of von Willebrand disease (VWD) on women's health, a retrospective cohort study was conducted using UK Clinical Practice Research Datalink (CPRD) GOLD database and Hospital Episode Statistics (HES) Admitted Patient Care data from 1988 to 2016. Materials and Methods: Hysterectomy and heavy menstrual bleeding (HMB) events were identified by recorded disease/clinical codes and compared in women with and without VWD (matched 1:10 by birth and CPRD record start years [±2 years], and general practice attended). Incidence rates and incidence rate ratios (IRR) were calculated; risks were estimated using the Kaplan-Meier method. Results: HMB was recorded after cohort entry in 388 of 1,335 women (29.1%) with VWD and 1,524 of 12,463 women (12.2%) without VWD. The cumulative incidence of HMB was higher in women with versus without VWD across all ages (p < 0.0001), and irrespective of prior HMB status (p < 0.001). Women with VWD were more likely to have HMB compared with women without VWD; IRR adjusted for age and prior HMB status was 2.74 (95% confidence interval [CI]: 2.44-3.07). Hysterectomy was recorded in 88 of 1,374 women (6.4%) with VWD and 320 of 12,791 women (2.5%) without VWD. The cumulative incidence of hysterectomy was higher for women with versus without VWD (p < 0.0001), and highest among women aged ≥30 years at cohort entry. Women with VWD aged 30 - 39 years were more likely to undergo hysterectomy than women without VWD; IRR adjusted for prior HMB was 3.58 (95% CI: 2.36 - 5.44). Conclusions: These findings highlight the substantial impact of VWD on women's health.

Assessment of Iron Status in Adolescents Presenting to the Emergency Department With Heavy Menstrual Bleeding.

OBJECTIVE: Iron deficiency is extremely common in adolescents with heavy menstrual bleeding (HMB) presenting to the emergency department; however, patients are rarely screened for this. The objective of this study was to evaluate screening for iron deficiency in adolescents presenting to the emergency department for HMB. METHODS: This is a secondary analysis of a single-center, cross-sectional observational study using retrospective chart review. The study subjects are adolescents ages 11 to 19 years with International Classification of Diseases, Ninth Revision, Clinical Modification/International Classification of Diseases, Tenth Revision, Clinical Modification, codes for HMB who presented to the emergency department at a national tertiary care hospital from 2006 to 2018. Pregnant adolescents with HMB were excluded. Chart abstraction for demographic data, symptoms, laboratory tests, treatments, and outcomes was performed. The main outcome measure was the number of adolescents who had an iron evaluation in the emergency department and were discharged on oral iron. RESULTS: Of the 258 nonpregnant adolescents who sought care for HMB in the emergency department, 225 (87.2%) were evaluated with serum hemoglobin testing. Ninety-four (41.7%) of those tested were anemic. Only 23 of the 258 patients (8.9%) had iron studies (serum ferritin) performed; 18 of 23 (78.3%) had iron deficiency and 21 of 23 (92.3%) were anemic. Subjects presenting with fatigue, headache, or palpitations were more likely to have iron studies performed than those without these symptoms (all P < 0.01). Thirty-two of the 258 subjects (12.4%) were discharged on oral iron therapy, which included only 15 of the 18 subjects (83.3%) with iron deficiency determined by ferritin testing. CONCLUSIONS: Adolescents presenting to the emergency department with HMB are at significant risk of iron deficiency but are not being screened or treated, which may have significant consequences.

Association between menorrhagia and risk of intrauterine device-related uterine perforation and device expulsion: results from the Association of Uterine Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices are effective instruments for contraception, and 1 levonorgestrel-releasing device is also indicated for the treatment of heavy menstrual bleeding (menorrhagia). OBJECTIVE: To compare the incidence of intrauterine device expulsion and uterine perforation in women with and without a diagnosis of menorrhagia within the first 12 months before device insertion STUDY DESIGN: This was a retrospective cohort study conducted in 3 integrated healthcare systems (Kaiser Permanente Northern California, Southern California, and Washington) and a healthcare information exchange (Regenstrief Institute) in the United States using electronic health records. Nonpostpartum women aged ≤50 years with intrauterine device (eg, levonorgestrel or copper) insertions from 2001 to 2018 and without a delivery in the previous 12 months were studied in this analysis. Recent menorrhagia diagnosis (ie, recorded ≤12 months before insertion) was ascertained from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. The study outcomes, viz, device expulsion and device-related uterine perforation (complete or partial), were ascertained from electronic medical records and validated in the data sources. The cumulative incidence and crude incidence rates with 95% confidence intervals were estimated. Cox proportional hazards models estimated the crude and adjusted hazard ratios using propensity score overlap weighting (13-16 variables) and 95% confidence intervals. RESULTS: Among 228,834 nonpostpartum women, the mean age was 33.1 years, 44.4% of them were White, and 31,600 (13.8%) had a recent menorrhagia diagnosis. Most women had a levonorgestrel-releasing device (96.4% of those with and 78.2% of those without a menorrhagia diagnosis). Women with a menorrhagia diagnosis were likely to be older, obese, and have dysmenorrhea or fibroids. Women with a menorrhagia diagnosis had a higher intrauterine device-expulsion rate (40.01 vs 10.92 per 1000 person-years) than those without, especially evident in the first few months after insertion. Women with a menorrhagia diagnosis had a higher cumulative incidence (95% confidence interval) of expulsion (7.00% [6.70-7.32] at 1 year and 12.03% [11.52-12.55] at 5 years) vs those without (1.77% [1.70-1.84] at 1 year and 3.69% [3.56-3.83] at 5 years). The risk of expulsion was increased for women with a menorrhagia diagnosis vs for those without (adjusted hazard ratio, 2.84 [95% confidence interval, 2.66-3.03]). The perforation rate was low overall (<1/1000 person-years) but higher in women with a diagnosis of menorrhagia vs in those without (0.98 vs 0.63 per 1000 person-years). The cumulative incidence (95% confidence interval) of uterine perforation was slightly higher for women with a menorrhagia diagnosis (0.09% [0.06-0.14] at 1 year and 0.39% [0.29-0.53] at 5 years) than those without it (0.07% [0.06-0.08] at 1 year and 0.28% [0.24-0.33] at 5 years). The risk of perforation was slightly increased in women with a menorrhagia diagnosis vs in those without (adjusted hazard ratio, 1.53; 95% confidence interval, 1.10-2.13). CONCLUSION: The risk of expulsion is significantly higher in women with a recent diagnosis of menorrhagia. Patient education and counseling regarding the potential expulsion risk is recommended at insertion. The absolute risk of perforation for women with a recent diagnosis of menorrhagia is very low. The increased expulsion and perforation rates observed are likely because of causal factors of menorrhagia.

Adenomyosis: Diagnosis and Management.

Adenomyosis is a clinical condition where endometrial glands are found in the myometrium of the uterus. One in three patients with adenomyosis is asymptomatic, but the rest may present with heavy menstrual bleeding, pelvic pain, or infertility. Heavy menstrual bleeding is the most common symptom. Adenomyosis is distinct from endometriosis (the presence of endometrial glands outside of the uterus), but the two conditions often occur simultaneously. Risk factors for developing adenomyosis include increasing age, parity, and history of uterine procedures. Most patients are diagnosed from 40 to 50 years of age, but younger patients with infertility are increasingly being diagnosed with adenomyosis as imaging modalities improve. Diagnosis of adenomyosis begins with clinical suspicion and is confirmed with transvaginal ultrasonography and pelvic magnetic resonance imaging. Treatment of adenomyosis typically starts with hormonal menstrual suppression. Levonorgestrel-releasing intrauterine systems have shown some effectiveness. Patients with adenomyosis may ultimately have a hysterectomy if symptoms are not controlled with medical therapy.

Depression in Female Adolescents with Heavy Menstrual Bleeding.

OBJECTIVE: To assess the degree to which heavy menstrual bleeding is associated with depression, independent of hormonal contraception. STUDY DESIGN: We performed a retrospective cohort study of 1168 female adolescents 9-18 years old presenting to general pediatricians for heavy menstrual bleeding or well visits. Depression was the primary outcome and defined as a diagnosis in the health record. Univariable and multivariable regression models were fit to the data to identify factors associated with depression diagnosis. RESULTS: In total, 581 adolescents with heavy menstrual bleeding and 587 without heavy menstrual bleeding were included. Depression diagnoses occurred with greater frequency in youth with heavy menstrual bleeding compared with those without heavy menstrual bleeding (50.9% vs 24.2% P < .001; risk ratio 1.67, 95% CI 1.39-2.01) but did not significantly differ between those taking vs not taking hormonal contraception (risk ratio 0.99; 95% CI 0.84-1.17). Most patients with depression and heavy menstrual bleeding developed depression following or concurrent with heavy menstrual bleeding (261/296, 88%). Of these, 199 of 261 (76%) were treated with hormonal contraception, but the majority (168/199; 84%) were diagnosed with depression before initiation. CONCLUSIONS: Heavy menstrual bleeding is associated with depression diagnosis in female adolescents. The use of hormonal contraception was not associated with depression diagnosis in multivariable analysis, covarying heavy menstrual bleeding, age, body mass index, anxiety, sexual activity, and substance use. As hormonal contraception is often used to treat heavy menstrual bleeding, heavy menstrual bleeding may be partially driving previous reports of increased depression risk in those taking hormonal contraception.

Bleeding patterns in patients before and after diagnosis of von Willebrand disease: Analysis of a US medical claims database.

INTRODUCTION: Von Willebrand disease (VWD) is the most common inherited bleeding disorder. The bleeding phenotype is variable, and some individuals have persistent symptoms post-diagnosis. AIM: To characterize bleeding patterns in patients with VWD before and after diagnosis. METHODS: De-identified claims data for commercially insured patients in the IQVIA PharMetrics® Plus US database (Jan-2006 to Jun-2015) were extracted. Eligible patients had ≥2 claims for VWD (ICD-9 code 286.4), and continuous health-plan enrolment for ≥2 years before and after diagnosis. Bleeding event, treatment and treating-physician type were analysed for 18 months before and 7-24 months after diagnosis, according to pre-diagnosis bleeding phenotype (claims from one vs multiple bleed sites) and post-diagnosis bleeding status (resolved [no post-diagnosis bleed claims] vs continued [≥1 claim]). RESULTS: Data for 3756 eligible patients (72.6% female; 71.0% aged ≥18 years at diagnosis) were analysed. Overall, 642 (17.1%) and 805 (21.4%) patients had single- and multiple-site bleed claims pre-diagnosis, respectively, and 1263 (33.6%) patients (38.5% of women, 20.8% of men) continued to bleed post-diagnosis. Multiple-site bleeding was associated with pre-diagnosis heavy menstrual bleeding (HMB), oral contraceptive (OC) use and nasal cauterization. Continued bleeding post-diagnosis was associated with pre-diagnosis gastrointestinal bleeding, HMB and epistaxis; pre-diagnosis use of OCs, aminocaproic acid and nasal cauterization; and younger age at diagnosis. Few patients consulted a haematologist for bleed management. CONCLUSION: Many patients with VWD have persistent bleeding from multiple sites and continue to bleed post-diagnosis. Our findings suggest a need to optimize management to reduce the symptomatic burden of VWD following diagnosis.