Women have a greater risk of aneurysmal rupture compared with men, and this risk is not explained by differences in patient- and aneurysm-related risk factors, according to study findings published in the journal Stroke.

Previous research has found a higher risk of rupture among women compared to men, however, it’s unclear whether female sex is an independent risk factor for unruptured intracranial aneurysm (UIA) rupture. Researchers hypothesize a higher prevalence of patient- or aneurysm-related risk factors for aneurysmal rupture in women may account for the higher risk of aneurysmal rupture in this patient population. The objective of the current study was to assess sex differences in rupture rate while taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture.

Researchers conducted a pooled analysis of individual patient data from prospective cohort studies to determine whether sex is a risk factor for intracranial aneurysm rupture independent from other risk factors, including the Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm (PHASES) score, smoking, and a positive family history for aneurysmal subarachnoid hemorrhage (aSAH). They searched the Pubmed and Embase databases for all relevant studies on rupture risk through December 1, 2020.

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Participants’ rupture rate was analyzed in a per-patient analysis and a per aneurysm analysis with use of a Cox proportional hazard regression model.

Individual patient data were pooled from 9 prospective cohort studies with 9940 patients, 12,193 UIAs, and 24,357 person-years of follow-up. The cohort included 6555 women (mean age, 61.9 years; 77% Japanese) and 3385 men (mean age, 59.5 years; 75% Japanese). Women less frequently were smokers (20% vs 44%) and more frequently had internal carotid artery aneurysms (24% vs 17%) and larger aneurysms (≥7 mm, 24% vs 23%) than men, respectively.

The median PHASES score was similar in women (7.0 [range, 0-21]) and men (7.0 [range, 0-20]), and the mean PHASES score was 7.2 ± 3.2 in women and 7.4 ± 3.0 in men. The mean follow-up time was 2.4 ± 3.5 years (median, 1.5 years) for women and 2.5 ± 3.7 years (median, 1.5 years) for men.

Among the 226 patients who had a single or largest UIA rupture, 163 were women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]), and 63 were men (0.74%/person-years [95% CI, 0.58-0.94]).

Analysis showed an unadjusted women-to-men hazard ratio of 1.43 (95% CI, 1.07-1.93). After the researchers adjusted for PHASES score, smoking, and positive family history for aSAH, the women-to-men hazard ratio was slightly lower (1.39 [95% CI, 1.02-1.90].

A sensitivity analysis in patients with no missing data for smoking, hypertension, and family history of aSAH (n=9566) found similar but nonstatistically significant results.

Among several study limitations, selection bias may have occurred owing to participant loss to follow-up within each cohort. Also, most studies only had data on smoking at the time of UIA detection but not during follow-up, and Japanese patients were overrepresented compared with other populations.

“Our results show that UIAs in women have a higher rupture risk than UIAs in men, which is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture, being risk factors of the PHASES score, smoking, and a positive family history for aSAH,” the researchers stated. “When assessing the risk of rupture of UIAs in women, this higher risk should be taken into account and a more aggressive treatment approach in women as compared to men is justified.”


Zuurbier CCM, Molenberg R, Mensing LA, et al. Sex difference and rupture rate of intracranial aneurysms: an individual patient data meta-analysis. Stroke. Published online January 5, 2022. doi:10.1161/STROKEAHA.121.035187