Heavy menstrual bleeding with direct oral anticoagulants and vitamin K antagonists: a systematic review and meta-analysis

Heavy menstrual bleeding (HMB) is a clinically important but underrecognized complication of oral anticoagulation that can impair quality of life, cause of iron deficiency or anaemia, and lead to treatment interruption. We conducted a systematic review and meta-analysis to compare menstrual bleeding outcomes among direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). MEDLINE, Embase, Scopus, and Cochrane CENTRAL were searched from inception through February 2026. Random-effects meta-analyses pooled odds ratios (ORs) with 95% confidence intervals (CIs) for HMB, anticoagulant modification, treatment for menstrual bleeding, and hospitalization, transfusion, or procedural intervention. Twenty-five studies published from 2015 to 2025 were included; most were observational. Compared with apixaban, rivaroxaban was associated with higher odds of HMB [odds ratio (OR) 2.83, 95% confidence interval (CI) 2.11-3.81; I2 = 0%] and anticoagulant modification because of menstrual bleeding (OR 6.05, 95% CI 1.91-19.19; I2 = 0%). Hospitalization, transfusion, or procedural intervention did not differ significantly (OR 1.04, 95% CI 0.10-11.13). Compared with VKAs, rivaroxaban was associated with greater odds of requiring treatment for menstrual bleeding (OR 4.01, 95% CI 1.88-8.54), whereas estimates for HMB and anticoagulant modification were imprecise and nonsignificant. Pooled DOAC-VKA comparisons for HMB were inconclusive. Menstrual bleeding risk appears to vary by individual anticoagulant rather than uniformly across the DOAC class. Proactive assessment of menstrual symptoms and iron deficiency, and patient-centred anticoagulant selection, are warranted, particularly for patients with preexisting HMB or anaemia.