Hormone Therapy and Oral Contraception

Oral contraception and hormone therapy appear to increase hemorrhage risk.


A 2020 prospective observational study of 202 CCM patients examining a wide range of predictors of hemorrhage found that 26.2% of women who presented with a hemorrhage were taking a form of estrogen therapy (i.e., oral contraceptive, hormone replacement). The risk of hemorrhage appeared to be greater in those with sporadic lesions, possibly due to thrombosis in an associated DVA, causing blood to back up and placing the vessels at risk for hemorrhage.

This finding led to a second, larger prospective observational study focused exclusively on hormone use, published in 2023. In this study, 722 female patients were followed for up to five years. Of these, 137 (19%) used hormone therapy – either oral contraception or hormone replacement therapy – at some point. The patients who used hormone therapy were more likely to hemorrhage (33.6% versus 15.6%, p=0.015). The higher rate of hemorrhage remained true even if including only those using oral contraceptives.

This is an important finding that warrants further research. The researchers called for a more detailed analysis to identify factor that may make some women more likely to hemorrhage when taking hormones. The potential causes include the presence of a DVA, genetic factors that increase clotting, or lifestyle factors. using larger cohorts before strong recommendations can be made about any risk of estrogen use in CCM patients. There may also be genetic differences (genetic modifiers) between women who are most at risk for hemorrhage when taking estrogen versus those who appear to be at a lower risk.


Kelly D. Flemming, Shivram Kumar, Robert D. Brown Jr., Giuseppe Lanzino. Predictors of Initial Presentation with Hemorrhage in Patients with Cavernous Malformations. World Neurosurgery, Volume 133, January 2020, Pages e767-e773. https://doi.org/10.1016/j.wneu.2019.09.161.

Susanna M Zuurbier, Alejandro N Santos, Kelly D Flemming, Börge Schmidt, Ramazan Jabbarli, Giuseppe Lanzino, Ulrich Sure, Philipp Dammann. Female Hormone Therapy and Risk of Intracranial Hemorrhage From Cerebral Cavernous Malformations: A Multicenter Observational Cohort Study. Neurology, 2023 Apr 18;100(16):e1673-e1679. doi: 10.1212/WNL.0000000000206888. Epub 2023 Feb 8.