Spontaneous Intracerebral Hemorrhage in Men vs Women: Which Sex Has Better Outcomes?

Men vs women with spontaneous intracerebral hemorrhage (ICH) have larger bleeds and a higher risk for hematoma expansion, but a lower risk for poor outcomes, according to study results published in Annals of Neurology.

Limited information is available on the role of sex in severity and outcomes of ICH, a better understanding of which can inform future research and clinical implications.

Researchers conducted a meta-analysis to determine how ICH can differ between the sexes. The studies analyzed were the Ethnic/Racial Variation in Intracerebral Hemorrhage (ERICH) observational study, and the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2), the Factor Seven for Acute Hemorrhagic Stroke (FAST), and the Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation 3 (MISTIE-III) trials.

Eligible participants had nontraumatic ICH, defined as an acute neurologic deficit associated with new bleeding, as observed on computed tomography (CT) or magnetic resonance imaging (MRI). Brain bleeds were further classified based on their location: lobar or deep hemorrhages.

Exposure of interest was sex, as assigned at birth.

Functional outcomes at 3 months after an ICH were assessed using the modified Rankin Scale (mRS), with scores ranging from 0 (absence of disability) to 6 (death).

The researchers included data from a total of 4781 patients with ICH in the current analysis, of whom 74.6% had deep hemorrhages and the remaining 25.4% had lobar hemorrhages. A greater percentage of men vs women had deep hemorrhages (77.9% vs 69.9%, respectively).

In the primary multivariate analysis, the researchers found that men vs women had a 63% higher risk of developing a deep ICH (odds ratio [OR], 1.63; 95% CI, 1.39-1.92; P <.001). The researchers found that results of the secondary analysis, involving a 2-stage meta-analysis using fixed-effects, were consistent with those of the primary analysis. The researchers also noted consistency across studies.

Race and ethnicity were found to impact the association between sex and ICH location (interaction P =.02), with White and Hispanic men (ORs, 2.19 and 1.85, respectively; P <.001 for both) having more deep bleeds compared with Black or Asian men (OR, 1.06; P =.76 and OR, 0.84; P =.67, respectively).

In the primary analysis, men vs women with ICH had increased ICH volume (β, 0.16; 95% CI, 0.08-0.23; P <.001). Results of the secondary analysis were consistent with those of the primary analysis. Total heterogeneity was low. When stratified by ICH location, the male vs female sex had higher ICH volume in both lobar (β, 0.19; 95% CI, 0.03-0.34; P =.02) and deep hemorrhages (β, 0.15; 95% CI, 0.06-0.23; P <.001).

Approximately one-fourths of eligible patients with ICH had hematoma expansion on neuroimaging, with men having a 43% higher risk for hematoma expansion than women (OR, 1.43; 95% CI, 1.20-1.71; P ≤.001).

A total of 47.9% of patients had poor outcomes at 3 months (mRS score of 4-6), with men having a 24% lower risk for poor outcomes (OR, 0.76; 95% CI, 0.64-0.90; P =.001). Of note, the prevalence of poor outcomes among men vs women was 45.9% vs 51.0%, respectively (P <.001).

“Our results suggest that the biology and clinical trajectory are different in females and males with ICH, supporting sex-specific research in this condition,” the researchers concluded.