Csilla Manoczki, MD

Leppert MH, Burke JF, Lisabeth LD, Madsen TE, Kleindorfer DO, Sillau S, Schwamm LH, Daugherty SL, Bradley CJ, Ho PM, Poisson SN. Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults: Are Young Women Disproportionately at Risk? Stroke. 2022;53:319–327.

Historically, stroke epidemiological studies have reported a higher rate of incident strokes in men than women, regardless of age. In the last decade, increasing evidence suggest that there may be more complexity to this “gender gap”, including a shift towards increased incidence of ischemic strokes in younger women.

In this systematic review of 16 population-based studies with nearly 70,000 patients included between 2008 and 2021, stroke incidence rate ratios for women/men in adults younger than age 45 years were calculated and standardized for each study. Combined incidence rate ratios were estimated for three age groups (≤35, 35-45, ≤45 years), and by ischemic stroke vs. all stroke types. Overall effect on the estimates was calculated by the study weights based on variability of the incidence rate ratios.

Four studies reported a significant higher stroke incidence in women. Nine studies didn’t find significant difference between women and men aged under 45 years. However, 6 of these studies included less than 100 patients each. Three studies found higher stroke incidence rates in men, but notably in the older age group (35-45 years).

The effect size analysis showed an overall 44% higher incidence of ischemic stroke in women under 35 years of age (IRR: 1.44 [1.18-1.76], I2=82%). There was non-significant difference in the age group of 35-45 years (IRR: 1.08 [0.85-1.38], I2=95%).

Study findings contradict previous observations on gender differences in stroke. The reason for the higher stroke incidence in younger women is not well understood. Although there is probably increasing role of traditional risk factors in younger age groups, there is a lower prevalence rate of atherosclerotic disease in premenopausal women due to the protective effect of endogenous estrogens. Hence, other, non-traditional risk factors should be considered in this cohort of patients, such as pregnancy, hormonal treatment, migraine, autoimmune disease, rare thromboembolic and genetic causes.

Limitations of the review highlighted by the authors included the heterogeneity of the studies included, differences in methodology and design, ascertainment of diagnosis, sample size, and lack of differentiated between stroke types. Ethnicity, cultural, and socioeconomic factors might be also relevant, but were not included in this review due to limited data.

Further research is required to understand the findings and potential contributing factors in order to optimize stroke prevention in young women.