Female hormone therapy tied to intracranial haemorrhage risk in patients with cerebral cavernous malformations

The study's findings, published in Neurology, raise questions about female hormone therapy's safety in clinical practice among patients with cerebral cavernous malformation.

In analysing data from 722 female patients, the researchers found that using female hormone therapy (menopausal hormone therapy or oral contraception) was tied to an increased risk of subsequent intracranial haemorrhage (ICH). The risk was more prominent among female patients aged 10-44 using oral contraceptives.

The use of oral contraceptives (progesterone and/or estrogen) among women and girls of reproductive age and menopausal hormone therapy for postmenopausal women is known to raise the risk of venous thrombosis and stroke, the researchers noted. But not much is known about the effects of these drugs on the intracranial haemorrhage risk in CCM patients, which can result in stroke or seizures.

To fill this knowledge gap, Susanna M. Zuurbier, Amsterdam UMC in the Netherlands, and colleagues aimed to investigate the association between female hormone therapy and intracranial haemorrhage in female patients with cerebral cavernous malformations in two extensive prospective, multicentre, observational cohort studies.

Consecutive patients with cerebral cavernous malformation were included. A comparison of the association between female hormone therapy use and ICH occurrence duet to the CCM was drawn during five years of prospective follow-up. An additional systematic review was performed from inception to November 2, 2021, to identify studies and assess their intracranial haemorrhage incidence rate ratio according to the use of female hormone therapy.

The study revealed the following findings:

• Of 722 female patients aged ten years or older at cerebral cavernous malformation diagnosis, 137 used female hormone therapy at any point during follow-up.
• Female hormone therapy use (adjusted for age, mode of presentation, and CCM location) was associated with an increased risk of subsequent intracranial haemorrhage (33·6% versus 15·6% adjusted hazard ratio 1·56).
• Use of oral contraceptives in female patients aged 10-44 years adjusted for the same factors was associated with a higher risk of subsequent intracranial haemorrhage (adjusted hazard ratio 2·00).
• The systematic literature search showed no studies reporting on the effect of female hormone therapy on the risk of intracranial haemorrhage during follow-up.

The study provides Class III evidence that female hormone therapy raised the risk of intracranial haemorrhage in patients with CCM.

"Further studies evaluating clinical factors raising the risk of thrombosis may be useful to determine which patients may be most susceptible to intracranial haemorrhage," the researchers concluded.

Reference:

Female Hormone Therapy and Risk of Intracranial Hemorrhage From Cerebral Cavernous Malformations: A Multicenter Observational Cohort Study Susanna M Zuurbier, Alejandro N Santos, Kelly D Flemming, Börge Schmidt, Ramazan Jabbarli, Giuseppe Lanzino, Ulrich Sure, Philipp Dammann Neurology Feb 2023, 10.1212/WNL.0000000000206888; DOI: 10.1212/WNL.0000000000206888