Not just Risk, But Recovery: The Stroke Sex Divide in Women

FAST is the infamous acronym that can help us to recognise the signs of a stroke.  Face. Arms. Speech. Time. Within minutes, a stroke can cause permanent  damage, or even become fatal. Strokes are more common in women and risk increases with age - this could be due to a longer life expectancy than men, but emerging research suggests that there are sex-specific differences relating, not just to the risk of incidence, but to progression and outcomes. So, what are these differences? 

What is a Stroke?  

Cardiovascular diseases, including stroke, are the overall leading cause of death  around the world. Strokes are categorised into two main types: ischaemic and  haemorrhagic stroke. Ischaemic strokes are more common - accounting for around 87% of incidences - where an artery in the brain becomes blocked by a blood clot (or thrombus), limiting oxygen and nutrient supply to the brain. Haemorrhagic strokes occur when the artery bursts, causing bleeding in or around the brain.  

The Sex-Specifics 

According to scientific reviews of stroke research, women have an increased risk  of stroke from both ‘traditional’ and ‘non-traditional’ factors. From a ‘traditional’  factor perspective, stroke incidence increases as we age, particularly from 55  years old, with the risk doubling every ten years thereafter. For women, age can cause more significant changes than in men, including a higher chance of atrial fibrillation (irregular heartbeat), worsening lipid profiles (measurement of fat molecules), higher likelihood of hypertension and obesity, and risk of stroke relating to diabetes. Sex-specific, or ‘non-traditional’, risk factors are suggested to include age of first menstrual period (before 13 years old and above 17 years old), the menopause, pregnancy, and hormone therapy. However, research does suggest that men have their own ‘traditional’ and sex-specific risk factors, including higher tobacco usage, strokes relating to hyperlipidaemia, and decreasing testosterone levels. If both sexes are at increased risk with age, why are women still more likely to experience a stroke? 

In McKay et al’s. (2024) review of stroke and sex-difference literature, they suggested that ‘age-standardised’ stroke incidence and ‘death due to stroke’ have declined globally; however, women have a higher age-standardised stroke incidence, as well as older age at first incidence of stroke, compared to men (75.1 years vs. 71.1). Research from the US in 2019 uncovered that stroke was the third leading cause of death for women, whereas it was the fifth leading cause in men. Women’s longer life expectancy could provide some explanation for the higher prevalence of stroke, and strokes in older age; however, these sex-specific and health factors must be investigated in order to address the problem.  

Higher stroke vulnerability in women could also be attributed to hormones. A review from Haast et al. (2012) highlighted the potential relationship between sex-specific hormones and stroke. Some research has suggested that oestrogen and progesterone contain protective elements for vascular health. Oestrogen contributes to a reduction in inflammation and regulation of vasoactive factors, such as vasodilating prostanoids, which cause blood vessels to relax and increase blood flow. Progesterone has shown to reduce oxidative stress (reactive oxygen species) and artery-clogging plaques by inhibiting vascular smooth muscle cell proliferation. However, the protective element that these hormones offer could decrease during the perimenopause stage. This stage occurs before menopause and is characterised by a fluctuation of hormones, including a decrease in oestrogen. This transitional period could mark a pivotal point where vulnerability to stroke begins to increase for women.  

Animal studies investigating sex-specific hormones and stroke have further supported the protective effects of these hormones. Oestrogen has been found to reduce lipoprotein accumulation and dangerous blood clots, as well as protect against peripheral vascular and cerebral diseases. In men, the protective mechanisms of oestrogen and progesterone are less apparent due to lower circulating levels. Protective effects from hormones seemingly demonstrate how the risk of stroke can be reduced, for example by reducing the deterioration of lipoproteins, increasing blood flow, and reducing the risk of blood clots and artery blockages. However, the drastic changes to women’s hormones during the perimenopause stage could change the risks to vascular health; thus, altering the risks for stroke.  

Sex-specific differences don’t just lie within hormones and stroke risk. Women  tend to present with different stroke symptoms and outcomes compared to men, including a lesser likelihood to exhibit symptoms such as speech and coordination difficulties. However, women are more likely to experience urinary incontinence, loss of consciousness, vision problems, and forms of dysphasia. These differences may complicate treatment, and even diagnosis.  

Treatment and Outcomes  

Thrombolysis is one method of treatment for stroke, which involves the bursting or dissolving of blood clots to improve blood flow and prevent further damage. Whilst this treatment is administered to both men and women, the outcome of this method is unclear. Some research suggests that men tend to show better outcomes than women after treatment. Although treatment in stroke units is delivered equally, men appear to derive greater benefit from shorter hospital stays, whereas women exhibit less functional recovery and responsiveness to rehabilitation following stroke. More pronounced sex differences have been suggested in carotid surgery - a surgery that involves removing fatty plaque build-up in the neck to restore blood flow - designed to reduce the risk of stroke. Men appear to benefit more from this procedure than women, however, there have been suggestions that this may be because women tend to receive this treatment option less frequently. Several papers have also reported lower administration, and use, of stroke-related medications in women e.g., aspirin, statins, and warfarin. Therefore, with worse stroke severity in women than men, quality of life is also more greatly affected, increasing care dependency and reporting of post-stroke depression.  

What Can Be Done? 

The greater risk and outcome disparity following stroke in women demonstrates an urgent need for better research and a change in treatment approach. Understanding the sex-specific differences in stroke risk, presentation, and recovery may improve prevention and care for women. There should be closer monitoring of women during and after the menopause, taking frequent measurements of blood pressure, cholesterol, and weight, to calculate vascular risk. Alongside this, treatment and rehabilitation methods should be assessed frequently, by either improving the sex gap in treatment received by men and women, or researching new treatments that may benefit women more than existing methods. Expanding research into these sex-specific differences, and determining stroke risk and treatment outcomes in animal and human studies, will improve our knowledge of pathophysiology and treatment and ensure there is awareness about risk factors, so that lifestyle changes can be implemented for example, through fitness, diet, and quitting smoking.  

Strokes are a global health threat, and whilst they affect both men and women, the  burden for women is greater. The severity of this increased risk requires tailored  sex-specific approaches to reduce the impact of stroke. Next time you think of  FAST, remember: while the signs of stroke are universal, the risks and outcomes vary widely. Raising awareness of these differences could be key to saving more lives. 

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This article was written by Lily Wilson and edited by Rebecca Pope, with graphics produced by Ishika Joshi. If you enjoyed this article, be the first to be notified about new posts by signing up to become a WiNUK member (top right of this page)! Interested in writing for WiNUK yourself? Contact us through the blog page and the editors will be in touch.