Heavy menstrual bleeding (HMB) is prevalent, with consequences impacting quality of life from adolescence through adulthood. Several clinical tools have been developed to aid in HMB diagnosis, which must be coupled with a detailed menstrual history. The diagnosis of HMB should be accompanied by evaluation of coexisting iron deficiency or iron deficiency anemia with appropriate treatment, and importantly, an in-depth evaluation for an underlying etiology. HMB is a significant hallmark of a bleeding disorder (BD) in adolescents; BDs are not often investigated and are underdiagnosed due to knowledge gaps, inconsistent referral practices, and lack of coordinated management by primary care providers, hematologists, and gynecology providers. Due to several missed opportunities, there is a substantial diagnostic delay of an underlying BD resulting in significant morbidity, risk of bleeding with future hemostatic challenges, and subsequent impact on undiagnosed family members. This review highlights issues related to HMB, associated iron deficiency/iron deficiency anemia, and the diagnostic journey for adolescents with BDs, emphasizing the roles of providers, community members, and other stakeholders to mitigate obstacles and create solutions to develop improved pathways to access best care for this population.

First described 100 years ago, von Willebrand disease (VWD) is the most common inherited bleeding disorder, characterized by a quantitative or qualitative deficiency of von Willebrand factor (VWF), a large multimeric glycoprotein central to hemostasis. Despite its prevalence, VWD remains globally underdiagnosed. Accurate diagnosis requires thorough clinical assessment and specialized laboratory evaluation. Although international evidence-based guidelines have advanced care, significant diagnostic and management challenges remain. Management focuses on treating and preventing bleeding, ensuring periprocedural safety, and improving quality of life through individualized strategies and the use of various hemostatic agents and therapeutic strategies. Optimal management approaches in complex clinical scenarios remain challenging. In this comprehensive illustrated review, we cover the biology and physiology of VWF, along with the pathophysiology, diagnosis, and management of VWD. We review current clinical practice recommendations and provide practical guidance for challenging scenarios such as surgery, pregnancy, cardiovascular disease, aging, and acquired von Willebrand syndrome. We also highlight emerging therapeutics and models of care in VWD.

This study aimed to determine the national pooled prevalence of abnormal uterine bleeding (AUB), its subtypes, and dysmenorrhea among adolescent girls in India. We conducted a systematic review and meta-analysis following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, searching PubMed, Embase, and Web of Science from inception to December 4, 2024. Twenty nine observational studies involving adolescent girls aged 10-19 years, with sample sizes ranging from 127 to 2,000, conducted across India, were included. Due to high heterogeneity, pooled prevalence estimates were calculated using random-effects models. The pooled prevalence of AUB was 18.0% (95% confidence interval (CI), 14.0%-22.0%). Among AUB subtypes, oligomenorrhea (24%, 95% CI: 15%-34%) and metrorrhagia (24%, 95% CI: 4%-44%) were the most common, followed by menorrhagia (18%, 95% CI: 14%-23%). Additionally, the pooled prevalence of dysmenorrhea was notably high at 53% (95% CI: 46%-61%, I[2] = 99.4%). Significant heterogeneity (I[2] > 99.1%) and regional disparities in prevalence were observed across all analyses. This study found that about one in five adolescent girls in India experience AUB. These findings support the need for future studies to evaluate the effectiveness, accuracy, and feasibility of screening strategies for their widespread implementation.

The use of anticoagulation in reproductive-aged females increases the risk of heavy menstrual bleeding (HMB). Excessive blood loss from HMB can lead to iron deficiency (ID), without or with anemia (IDA). We investigated the frequency with which reproductive-aged female patients on anticoagulants undergo screening for and receive a diagnosis of ID/IDA. We conducted a retrospective cohort study using the TriNetX global dataset of females aged 18-55 without a diagnosis of cancer who started anticoagulation therapy. The cohort was divided into sub-groups based upon ferritin testing within 90 days of starting anticoagulation and descriptive statistics were calculated. The initial cohort included 1,463,349 unique female patients across 93 healthcare organizations. Exclusion of those with cancer and those without laboratory values resulted in a final cohort of 783,196. Out of the final cohort, 9.2% had a ferritin level checked within 90 days of starting anticoagulation. Of those, 36.6% had a ferritin level ≤ 50 ng/mL while 25.8% had ferritin levels ≤30 ng/mL. Among individuals with ferritin ≤30 ng/mL, 19.7% (n = 3655) had a hemoglobin ≥12 and 44.0% (n = 8170) had MCV < 80 fL. These findings highlight a significant gap in the evaluation of ID for reproductive-aged females taking anticoagulation and emphasize the importance of using ferritin for the diagnosis of ID with or without anemia. Future studies and interventions are indicated to increase screening and expedite treatment of ID/IDA in reproductive-aged female patients starting anticoagulation.

A 37-year-old non-Caucasian woman presented with a 2-year history of pruritic, concentric erythematous plaques refractory to multiple topical and systemic therapies. The clinical findings were highly suggestive of erythema gyratum repens (EGR), a rare figurate dermatosis classically associated with paraneoplastic syndromes. Routine laboratory investigations and an autoantibody panel were unremarkable, except for a significantly elevated CA-125 level. A targeted gynecological assessment, prompted by a chronic history of pelvic pain and menorrhagia, identified severe adenomyosis with concomitant endometriosis. Given the severity of her symptoms, the patient underwent a total hysterectomy. Following surgery, the cutaneous eruption resolved completely within 2 months without additional dermatologic intervention. This case broadens the spectrum of non-paraneoplastic conditions associated with EGR and suggests that such eruptions may arise within the context of chronic inflammatory gynecological disease. Clinicians should remain aware of both paraneoplastic and non-paraneoplastic etiologies in patients presenting with EGR to ensure accurate diagnosis, appropriate malignancy screening, and tailored management.

Bleeding disorders represent a broad spectrum of conditions that disrupt normal clot formation through abnormalities in platelet function or the coagulation cascade. Disorders affecting primary hemostasis typically manifest as mucosal bleeding, whereas abnormalities in secondary hemostasis more often lead to deep tissue hemorrhage. However, certain conditions, such as von Willebrand disease, may involve features of both pathways, complicating clinical evaluation. This report describes two adolescent patients who presented with mucocutaneous bleeding but were ultimately diagnosed with different underlying conditions: Glanzmann thrombasthenia and type 2 von Willebrand disease. The first patient exhibited recurrent gingival bleeding with normal platelet counts and near-normal coagulation studies. Further evaluation using platelet aggregation testing revealed impaired responses to multiple agonists, consistent with a defect in platelet aggregation. The second patient presented with gingival bleeding and severe menorrhagia and was initially treated as a case of hemophilia due to reduced factor VIII levels. Lack of therapeutic response prompted further testing, which demonstrated abnormal von Willebrand factor activity, confirming a qualitative defect. These cases highlight the importance of correlating clinical presentation with specialized laboratory investigations. Reliance on routine tests alone may lead to misdiagnosis, whereas a systematic diagnostic approach allows accurate identification and appropriate management of bleeding disorders.

The TSC complex, formed by the binding of TSC2 with TSC1 and TBC1D7, plays an important role in the onset of endometrial-related diseases through the TSC-mTORC1 axis. However, the relationship between these proteins and adenomyosis has not been determined thus far. Here, we aimed to investigate the expression of TSC proteins in adenomyosis and determine the correlation between TSC expression and clinicopathologic parameters in patients with adenomyosis. 21 patients (age range, 40-50 years) with histologically diagnosed adenomyosis who underwent hysterectomy for nonendometrial disease were enrolled in this study. Specimens of healthy endometria were obtained from 21 patients (age range, 38-53 years) with cervical carcinoma in situ who underwent laparoscopy. The participants were interviewed via a standard questionnaire consisting of items pertaining to sociodemographic characteristics and reproductive history. The severity of dysmenorrhea and menorrhagia was quantified by means of the visual analogue scale and the menstrual pictogram, and preoperative hemoglobin levels were determined. Samples of serum and endometrial tissue were collected, TSC and VEGF expression was determined via immunofluorescence, and VEGF expression in the serum was quantified via ELISA. We found that, in patients with adenomyosis, TSC expression was significantly decreased during the secretory phase. Endometrial TSC1 and TSC2 expression was correlated with menstrual volume. Additionally, high levels of VEGFD increased the likelihood of moderate-to-severe menorrhagia in adenomyosis patients. Our results suggest that TSC is associated with clinical symptoms such as menorrhagia. In addition, VEGFD may be a potential quantitative predictor of the severity of menorrhagia in patients with adenomyosis.

Adenomyosis is a chronic gynecological disorder characterized by ectopic endometrial tissue within the myometrium, leading to pelvic pain, menorrhagia, and infertility. Increasing evidence implicates dysregulated Wnt/beta-catenin signaling and aberrant activation of SFRP4+ natural killer T (NKT) cells in disease progression. This study reports the ultrasound-assisted synthesis of a cerium-doped zeolite nanocomplex (Ce-ZNC) and evaluates its therapeutic efficacy in experimental models of adenomyosis. Ce-ZNC was synthesized via an ultrasound-assisted doping approach and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and polydispersity index (PDI) analysis. In vitro studies were conducted on human peripheral blood mononuclear cell (PBMC)-derived SFRP4+ NKT cells. In vivo efficacy was evaluated in a murine adenomyosis model. IGFBP5 expression and Wnt/beta catenin signaling components were analyzed by RT-qPCR and Western blotting. Histological and cytokine analyses were performed to assess fibrosis and inflammation. Ce-ZNC exhibited spherical morphology with nanoscale dimensions and good colloidal stability. Treatment resulted in a dose-dependent suppression of IGFBP5 expression and inhibition of Wnt/beta-catenin signaling. In vivo administration significantly reduced uterine fibrosis, glandular invasion, and inflammatory cytokine levels. These findings suggest that Ce-ZNC exerts immunomodulatory and anti-fibrotic effects in adenomyosis. While promising, further studies are required to elucidate biodistribution, long-term safety, and translational potential in human models. Key words Adenomyosis " Cerium-doped zeolite " Nanomedicine " Wnt/beta-catenin pathway " IGFBP5 " SFRP4+ NKT cells " Inflammation " Fibrosis " Ultrasound-assisted synthesis.