Menstrual outcomes are frequently overlooked in von Willebrand disease trials

Abstract

Background: Despite autosomal inheritance, females are disproportionately impacted by von Willebrand disease (VWD) due to heavy menstrual bleeding (HMB). HMB remains the most frequently reported and severe bleeding symptom in females with VWD. Nevertheless, interventional studies of VWD prophylaxis frequently fail to include or report menstrual-related outcomes. Objectives: This study evaluated the inclusion of menstrual and female-specific outcomes in clinical interventional trials of VWD prophylaxis. Methods: US (Clinicaltrials.gov), Canadian (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/health-canada-clinical-trials-database.html), and European (clinicaltrialsregister.eu) databases were searched for VWD interventional studies open to females with VWD aged >12 years between 2014 and 2024. Two reviewers assessed all studies, excluding those not focused on prophylaxis or duplicates. Inclusion criteria, outcomes, and publications were reviewed for menstrual-related data. Results: Initially, 42 interventional studies were identified; following exclusions, 10 studies remained. Only 2 of 10 (20%) studies incorporated menstrual inclusion criteria. Furthermore, 4 of 10 studies specifically excluded treated menstrual bleeding in their bleed eligibility criteria. Annualized bleeding rates were collected in 8 of 10 (80%) studies but menstrual outcomes in only 4 of 10 (40%). Most studies with results posted (n = 7) reported age (7/7) and sex (6/7) of participants; however, lack of overlapping data limited identification of females of menstrual age. Overall, identified females of menstrual age comprised 65 of 185 participants (35%) recruited. Conclusion: Clinical trials in VWD frequently use outcomes adapted from hemophilia studies (eg, annualized bleeding rates) rather than tailoring to the needs of females with VWD. Until we address this issue, we will lack clarity on optimal treatment, including the role of prophylaxis for the management of HMB in females with VWD.