Impact of Sex and Gender in Stroke in South and Southeast Asia: A Rapid Scoping Review

South Asia and Southeast Asia together constitute around one-fourth of the total world’s population and is one of the most geographically and socioculturally diverse regions of the world. Geographically, South Asia consists of 8 countries: Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka, and Afghanistan. Southeast Asia refers to the geographical southeastern region of Asia constituting 11 countries: Brunei, Cambodia, East Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam. Interestingly, the World Health Organization (WHO) defines the Southeast Asian region with overlapping countries from both geographical regions including the following countries: Bangladesh, Bhutan, Democratic People’s Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, Timor-Leste. Therefore, for the purpose of this review, we included countries from both South Asia and Southeast Asia. Currently, this region accounts for almost half of the developing world’s stroke burden [1].

The impact of sex and gender differences in stroke is a well-described yet complex subject. Both biological sex (referring to the genetic and biological characteristics of the individual), as well as the sociocultural construct of gender (which includes gender identity, expression, and stereotypic roles for male, female, and gender-diverse people), can contribute to differences in stroke [2]. The interrelation and intersection of sex and gender with other social determinants such as race, ethnicity, social, and financial status, makes it extremely challenging, if not impossible to dissociate the individual impact of these different determinants. Furthermore, while geographical and sociocultural settings may be assumed not to affect biological sex-related factors, the impact of the same on gender-related factors affecting stroke may differ based on regional and cultural shifts.

Sex and gender differences in stroke within South and Southeast Asia present a multifaceted challenge with significant implications for healthcare delivery and outcomes. However, there is a paucity of comprehensive epidemiological data from this region. Much of the information is gained from region-specific hospital-based registries with substantial methodological variations. Additionally, the published literature does not explicitly account for sex or gender and likely represents the combined impact of both influences.

In this review, we summarize the sex and gender differences in stroke burden and stroke service provision across South Asia and Southeast Asia. Several key themes emerge with unique epidemiological trends in stroke incidence, prevalence, and risk factors. Women are disproportionately affected in terms of stroke severity, mortality, and response to treatment. Furthermore, cultural practices and socioeconomic disparities contribute to differential access to acute treatment options and poststroke care.

The review was designed and conducted in accordance with PRISMA-ScR 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search strategy (included keywords associated with “stroke” “gender disparity,” “South Asia,” “Southeast Asia” and “SEAR countries”) was run on OVID, PubMed, Embase, CINAHL, Web of Science, and EBSCO databases. Two levels of screening by independent reviewers were performed based on predefined selection criteria. Detailed descriptions of the search methodology and PRISMA flowchart are provided in Supplement 1 (for all online suppl. material, see https://doi.org/10.1159/000542010).

A total of 3,798 articles were identified, of which 35 articles provided relevant information and were included. Characteristics of the included studies and JBI scores for types of studies are provided in online supplementary 2. Key findings from the results are shown in Figure 1.

The GBD 2019 data estimates the incidence of stroke in South and Southeast Asia to be more than a million people and the prevalence to be around 10 million per year. The highest incidence and prevalence are reported from India, and the lowest from Maldives [3]. Age-adjusted prevalence of stroke in the region ranges from 44–843 per 100,000 people [4]. Similar prevalence is reported from Pakistan (1.2%), Bangladesh (1%), and Sri Lanka (1.04%). Mean age in Indian studies is significantly lower (<60 years) than the Western population, explained by the higher prevalence of vascular risk factors [5, 6]. In India, age-standardized incidence of stroke among men ranged from 141–162 per 100,000 person-years, compared to 128–143 per 100,000 in women [7]. Studies from India have reported a higher incidence of stroke among women than men (149.49 vs. 99.54 per 100,000 persons/year) [8].

Stroke is the leading cause of mortality in Indonesia, Myanmar, and Vietnam, and the second-leading cause in Malaysia [9]. Mortality rates after stroke appear to be higher in Asian women than men, being more pronounced among the elderly and those with atrial fibrillation (AF). The National Stroke Registry in Singapore reported higher mortality rates among women with variations across age groups, stroke subtypes, and geographical regions. Similarly, Nepal [10] reports higher stroke mortality in women; however, Vietnam and Myanmar report higher mortality among men [11]. In a meta-analysis of 13 studies by Guo et al. [12], mortality in stroke patients in the first year (OR: 0.82; 95% CI: 0.69%–0.99%; p = 0.03), as well as at 10 years was more in males than females (OR: 0.72, 95% CI: 0.65%–0.79%, p < 0.00001). However, females had significantly poorer outcomes than males (OR: 1.36, 95% CI: 1.24%–1.49%, p < 0.00001). Contrastingly, an intracerebral hemorrhage (ICH) study from India estimated poor outcomes dependent on hematoma size, blood pressure (BP), and intraventricular extension but not on age or gender [13]. Another analysis reported higher inhospital stroke mortality in women (risk: 1.03; 95% CI: 1.01–1.04, n = 192,826), but no differences with gender after discharge [14].

In addition to a higher prevalence of conventional risk factors such as AF, diabetes, hypertension, and depression, women also carry the risk of hormone-specific factors. In the INTERSTROKE study, hypertension (population attributable risk [PAR] = 52.3%), waist-to-hip ratio (PAR = 25.8%), and adverse lipid profile (PAR = 29.2%) were the most impactful risk factors for stroke in women [15]. BP control often proves more difficult in elderly women poststroke contributing to higher mortality rates. In southern India, women were older, had poorer lipid control with a higher prevalence of cardioembolic (27.2% vs. 19.7%, p = 0.02), and more severe (mean NIHSS: 9.5 vs. 8.4, p = 0.03) strokes [6]. Of 958 women from 9 Asian countries, 19% had cardioembolic strokes [16].

Compared to other parts of the world, smoking is less prevalent among South Asian women. The highest rates of smoking and secondhand smoke from South and Southeast Asia are reported from Maldives and Indonesia [17]. However, consumption of tobacco without burning, also known as smokeless tobacco (SLT), is highly prevalent in this region. Different forms of SLT such as snuff, betel nut, and tobacco leaf chewing are more prevalent among women than men (28 vs. 21%) [18], with higher rates reported from Bangladesh, Indonesia, and Thailand. In a study from Pakistan, 4.65% of women used SLT compared to 1.85% who smoked tobacco. Poor socioeconomic status and lower levels of education were found to be independently associated with tobacco use [19].

Household air pollution from use of solid fuels is another risk factor for women, especially those in rural regions. A study among rural Indian women reported acute increases in systolic BP associated with exposure to biomass fuels, which may affect cardiovascular health [20]. Highest rates of household pollution have been reported in Timor-Leste (32.6%) and Myanmar (26.5%), while ambient particulate matter pollution was highest in Bangladesh (40.2%) followed by India (25.5%) and Thailand (22.3%) [3].

South Asia reports a higher prevalence of ICH (19–46%) compared to the global frequency of 20% [21]. However, some studies have reported a lower incidence in women. In a multiethnic Asian cohort, women had a lower occurrence of ICH till 80 years of age, beyond which the trend reversed [22]. Cerebral venous sinus thrombosis (CVST), a venous stroke subtype, is more common in South and Southeast Asia with a higher predilection for women. Among 110 women from 8 Asian countries, Khan et al. [23] found 49.1% of all strokes to be venous in etiology. Sociocultural practices, such as water restriction during puerperium, and anemia have been considered to contribute. A study from southern India reported fluid restriction in 77.1% of puerperal women admitted with CVST [24]. However, similar to developed countries, oral contraceptive pills (OCPs) too are emerging as a risk factor for CVST in this region. A South Asian study, where women constituted 33% of all strokes, reported CVST as one of the commonest subtypes of stroke (20%) of which 10% was attributed to OCPs [16]. This cohort had a lower age compared to Western literature.

South and Southeast Asia has poor public awareness of stroke risk factors, symptom presentation, and overall health outcomes regardless of gender [25]. Interestingly, a survey of school students in Pakistan revealed a greater understanding of stroke symptoms among female students (61 vs. 30%). Despite this, only 23% expressed the need to seek medical help [26]. Higher education was associated with better awareness of stroke in Sri Lanka; however, poorer opportunities for education among women imply lower awareness in this group [27].

Women may frequently present with atypical stroke symptoms such as isolated headaches, confusion, or sensory predominant symptoms, leading to misdiagnosis [28]. Whether atypical symptoms are truly higher in women is uncertain, given the presence of unadjusted confounders like age and coexisting psychosomatic disorders in many studies. Furthermore, women are more prone to migraine which can mimic stroke, compounding the challenge of timely diagnosis. Though Western literature reports high frequency of stroke in women with migraine, comparable data are lacking from Asian studies.

Historically, women with suspected stroke are less likely to receive intravenous thrombolysis (IVT) despite presentation within similar times as men. Resonant with the above, studies from South and Southeast Asia have demonstrated that women were less likely to reach hospital within 3 h of stroke onset, with greater delays in IVT workflow times, and presentation with more severe strokes making them ineligible for IVT [29]. Another study reported no gender differences in IVT rates or door-to-needle times [16]. Sufficient literature is lacking from the region with regards to gender differences in EVT utilization; however, a pooled analysis from Asia noted no such differences [30]. Despite an elevated stroke risk in pregnancy, we only found a few select case reports of reperfusion therapy offered in this cohort [31].

There emerges a bias in favor of men on examining the healthcare-seeking patterns. In a gendered analysis based on cross-sectional surveys in India, women were more likely to be treated in public hospitals (51.8% vs. 32.6%), utilize general wards, and were more likely to discontinue treatment (20% vs. 13%), while men were more likely to avail private healthcare (67.4% vs. 48.2%). In 2014, the overall mean medical and rehabilitation expenditure was consistently higher for men and despite a decrease by 2018, the gap remained high [7].

Concerning access and use of stroke rehabilitation, men seem to derive a disproportionate benefit without much exploration of the causes of this disparity. Studies have reported a better 3rd or 6th month functional outcome among men compared to women in stroke trials [32]. Studies report increased duration as well as expenditure for stroke rehabilitation among men. In a hospital-based sample, Mahak et al. [33] reported 21.9% of women utilizing rehabilitation services compared to 38.1% of men. With respect to quality of life, data were conflicting with some studies reporting no significant differences in poststroke depression [13], while others showed greater improvement in quality of life among women. Despite being worse than men at baseline, there were no sex differences in 3-month motor or cognitive performances [34].

Singapore is one of the few nations where gender was not a predictor of poststroke participation in activities or poststroke outcomes [35]. In contrast, an inhospital prospective study associated male gender with improved poststroke functional outcomes. Females had a higher likelihood of urinary tract infection, urinary retention, and depression, all of which can directly affect recovery and functional status [36]. The ATTEND trial in India showed poorer premorbid and discharge Rankin scores and poorer long-term outcomes in women [37]. Sri Lanka reports no gender-related inequity in stroke-related treatments barring a higher receipt of lifestyle modifying treatment among men.

This review provides a comprehensive synthesis of the implications of sex and gender on stroke and its outcomes, within South and Southeast Asia. High-quality epidemiological data are lacking from this region, with most available data originating from a select few countries that may not depict the narrative of the entire region. Further, the lack of methodological homogeneity makes comparisons between the data challenging.

Historically, women have a lower incidence of stroke till menopause after which this risk equalizes; however, more recent literature suggests a similar stroke risk even among younger women. We found conflicting epidemiological data in our cohort; however, overall women tended to have poorer outcomes poststroke. Women are older with more comorbidities and preexisting disability at the time of their first stroke which likely contributes to a poorer return to function. A high prevalence of cardioembolic strokes was also seen among women in our cohort. Previous studies have reported disparities in cardiac monitoring in women [5]. Elderly women with AF are at a higher risk of subsequent strokes warranting a thorough search for arrhythmia during stroke assessments. No sex-specific differences were reported in the major direct oral anticoagulants trials but had underrepresentation of women. More sex-disaggregated data in terms of response, safety, and outcomes with direct oral anticoagulants are needed.

The lower incidence of smoking among women in this region is notable compared to 10% smoking related strokes in developed countries. Nevertheless, there is cause for concern in countries like Pakistan and Bangladesh where high consumption of SLT use among women is reported. An estimated 100 million consumers of SLT have been reported from India and Pakistan alone. Easy availability, sociocultural practices, and misconceptions around its relative safety encourage its use, especially among lower socioeconomic classes [38]. Exposure to household air pollution from the combustion of biomass (wood, crop residues, and dung) has been associated with an increase in BP and higher cardiovascular risk [20, 39]. Traditional stoves using solid and biomass fuels for cooking, still used in many parts of Timor-Leste and India, pose a substantial cardiovascular risk with women being more at risk of exposure in contrast to developed countries. Policies aimed at awareness, supplemented with initiatives implementing alternative measures such as liquefied petroleum gas, are imperative. The frequency of CVT in peripartum women has decreased over the years reflecting the improving maternal and child services in these regions. Though sociocultural traditions specific to the region such as postpartum fluid restriction, dehydration, and anemia have been associated with the high prevalence, establishing causality is difficult given the methodological heterogeneity in studies. Other variables such as OCP use, increased parity (>5 live births), and shorter duration of breastfeeding have also been reported [40]. Notable findings with respect to sociocultural practices influencing gender disparities in stroke care have been listed in Table 1.

We found heterogenous data concerning IVT in women, with delays in onset-to-door times, but none in door-to-needle times. A meta-analysis on sex-specific differences in IVT use determined 13% lower odds of women receiving IVT compared to men. These findings were more pronounced in Europe and the USA but not in Asia and Germany. While this resonates with the findings in our review, we must consider the limitations of our data originating from a few hospital-based studies. The higher prevalence of cardioembolic strokes with subsequent large vessel occlusions and more severe strokes at presentation explains the lower utilization of IVT in women. We found no differences in EVT utilization in our cohort, though this may partly be due to inadequate accessibility.

Despite a higher awareness of stroke among women in some countries, translation of the same into prompt action remains a challenge. Glaring gender disparities in the level of care even upon reaching a hospital are concerning but have not been explored much, except for generalizations from perspectives of regional and cultural beliefs and practices. Smith et al. [41] describe that for many households, regaining normal functioning for women may not be a priority at all. Prevalence of traditional gender roles, with men being the custodians of income and the decision-makers, often results in a low investment of efforts, and finances toward the health needs of women. Notably, there are no sex differences in the effects of exercise on the cognitive or executive functioning in individuals with stroke, and therefore, there is no rationale for incorporating sex into our clinical decision-making for rehabilitation.

Evidence from clinical trials informs our clinical practice; however, the inadequate representation of women is a lacuna that needs to be acknowledged. It is a vital need to better represent women, especially older women who are most at risk of stroke. Much is still lacking in our understanding of the response and outcomes to stroke among men and women. We recommend strategies beyond public awareness programs that involve national/regional government schemes offering inexpensive stroke care packages for women, female champions/ambassadors in policy/public health/research related decision-making processes, private insurance schemes specialized for the needs of women with stroke, and lastly, inclusion of information of such glaring disparities in the medical and allied health curriculum to prepare the next generation of medical/paramedical professionals.

This study has important limitations to consider. Most of the data were sourced from hospital-based registries which may not accurately reflect the community incidence of stroke. The decision to include English-only publications may omit relevant studies published in local languages. Due to a lack of methodological homogeneity, a narrative synthesis approach was performed. While necessary, it omits quantitative data analysis which may limit study findings.

Biological factors interwoven with sociocultural constructs impede the equitable provision of stroke care among women in South and Southeast Asia. Future directions to improve equity of care should be targeted at interventions to improve awareness of stroke and its risk factors. Global/regional awareness campaigns such as those led by the World Stroke Organization, WHO-SEAR are notable. Policies for access to stroke care and rehabilitation, with opportunities for insurance schemes/subsidies, need to be implemented with appropriate stakeholder involvement. It is essential to be cognizant of the gender and cost bias in the region, as well as the regional/local belief systems and family structures when formulating policies/programs viable for women. Stroke research is a relatively newer field needing evaluation of gender-based differences in stroke and inclusion of females with stroke in decision-making. Adequate gender representation in stroke clinical trials, especially in the context of their sociocultural environments is essential.

An ethics statement was not required for this study type since no human or animal subjects or materials were used.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

I.A.S. and D.G. conceptualized the review. D.G., J.S., R.M., V.B., and V.M. contributed to data extraction. D.G., I.A.S., J.S., R.M., V.B., and V.M. conducted the narrative data synthesis and charting. D.G., I.A.S., and R.M. contributed to data interpretation and quality analysis. D.G., I.A.S., R.M., and J.S. led manuscript writing and editing, while D.G., I.A.S., and R.M. contributed to the final approval of the manuscript.

All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.