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Original Investigation
January 2017

Female- and Male-Specific Risk Factors for Stroke: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands
  • 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
  • 3Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
JAMA Neurol. 2017;74(1):75-81. doi:10.1001/jamaneurol.2016.3482
Key Points

Question  What are sex-specific characteristics that influence the risk of ischemic stroke, hemorrhagic stroke, any stroke, or stroke mortality?

Findings  In this systematic review and meta-analysis, female-specific characteristics associated with increased stroke risk included hypertensive disorders of pregnancy for ischemic stroke, late menopause and gestational hypertension for hemorrhagic stroke, and oophorectomy and various pregnancy complications for any stroke; hysterectomy might be a protective factor against any stroke. Male-specific risk factors were low induced testosterone levels for ischemic stroke and any stroke and erectile dysfunction for any stroke.

Meaning  The accuracy of risk assessment of stroke can be improved by adding female- and male-specific protective or risk factors to risk scores.


Importance  The incidence of stroke is higher in men than in women. The influence of sex-specific risk factors on stroke incidence and mortality is largely unknown.

Objective  To conduct a systematic review and meta-analysis of female- and male-specific risk factors for stroke.

Data Sources  PubMed, EMBASE, and the bibliographies of articles were searched for studies published between January 1, 1985, and January 26, 2015, reporting on the association between female- and male-specific characteristics and stroke.

Study Selection  Observational studies reporting associations between sex-specific risk factors and stroke were selected.

Data Extraction and Synthesis  Two authors performed data extraction independently. Estimates were pooled with a generic variance-based, random-effects method. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. In addition, our study adhered to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.

Main Outcomes and Measures  Ischemic stroke, hemorrhagic stroke, any stroke, and stroke mortality.

Results  This systematic review and meta-analysis included 78 studies (70 longitudinal and 8 case-control) comprising 10 187 540 persons. In women, the pooled relative risks of ischemic stroke were 1.80 (95% CI, 1.49-2.18) after any hypertensive disorder in pregnancy (HDP) (gestational hypertension [GH], preeclampsia, or eclampsia) and 1.81 (95% CI, 1.44-2.27) after GH vs no HDP. The pooled relative risks of hemorrhagic stroke were 2.24 (95% CI, 1.19-4.21) in women with menopause at the age of at least 55 years vs 50 to 54 years and 5.08 (95% CI, 1.80-14.34) after GH vs no GH. The pooled relative risks of any stroke were 1.42 (95% CI, 1.34-1.50) after oophorectomy vs no oophorectomy, 0.88 (95% CI, 0.85-0.90) after hysterectomy vs no hysterectomy, 1.63 (95% CI, 1.52-1.75) after any vs no HDP, 1.54 (95% CI, 1.39-1.70) after preeclampsia or eclampsia, 1.51 (95% CI, 1.27-1.80) after GH vs no HDP, 1.62 (95% CI, 1.46-1.79) after preterm delivery, and 1.86 (95% CI, 1.15-3.02) after stillbirth vs no pregnancy complications. The pooled relative risk of stroke mortality was 1.57 (95% CI, 1.04-2.39) after GH vs no GH. In men, the pooled relative risks of ischemic stroke were 1.19 (95% CI, 1.05-1.34) after androgen deprivation therapy (ADT) vs no ADT and 1.21 (95% CI, 1.00-1.46) after orchiectomy vs no orchiectomy. The pooled relative risks of any stroke were 1.21 (95% CI, 1.06-1.37) for ADT vs no ADT and 1.35 (95% CI, 1.18-1.53) for erectile dysfunction vs no dysfunction.

Conclusions and Relevance  Female-specific characteristics increasing stroke risk include HDP for ischemic stroke, late menopause and gestational hypertension for hemorrhagic stroke, and oophorectomy, HDP, preterm delivery, and stillbirth for any stroke. Hysterectomy is possibly protective against any stroke. Male-specific characteristics increasing stroke risk include medical androgen deprivation therapy for ischemic and any stroke and erectile dysfunction for any stroke. Consideration of sex-specific risk factors can improve individualized stroke risk assessment.