How I Treat Heavy Menstrual Bleeding in Patients with Bleeding Disorder of Unknown Cause

Bleeding disorder of unknown cause (BDUC) describes patients with a clinically relevant bleeding phenotype despite normal routine hemostatic testing. Heavy menstrual bleeding (HMB) is among the most common symptoms in BDUC, alongside other muco-cutaneous bleeding manifestations. We recommend that women presenting with HMB undergo a systematic evaluation for an underlying bleeding disorder. This assessment should include a structured bleeding and family history, exclusion of acquired causes of bleeding, and comprehensive laboratory investigations. In case of a clinically relevant bleeding phenotype and normal hemostatic results, the diagnosis of BDUC can be established. In BDUC, targeted hemostatic treatments are not available. Management of HMB in BDUC requires an interdisciplinary, multimodal approach that includes hormonal therapy including intrauterine devices, antifibrinolytics and, in selected cases, surgical or other invasive interventions. Iron deficiency is frequent in women with HMB and BDUC and contributes substantially to fatigue and impaired quality of life, thus requiring targeted screening. Despite the considerable clinical burden, evidence to guide management of HMB in women with BDUC remains limited. Here, we report on representative clinical cases to highlight key challenges, summarize the available evidence, and outline a pragmatic approach for the management of HMB in patients with BDUC.