Controversial results have been reported on the impact of sex differences on stroke risk factors, clinical presentation and functional outcomes of AIS receiving rTPA.

This is the first study from Upper Egypt to assess the influence of sex on stroke risk factors, presentation, and 3-month outcomes of rTPA-treated patients. The main findings were that a smaller proportion of females received rTPA than males. Females had a higher rate of hypertension and AF as risk factors for stroke, with cardioembolic stroke being more prevalent compared to males. In addition, the onset-to-door and onset-to-needle times were significantly faster than in males. Sex distribution did not affect the primary Outcome or death rate. However, re-infarction was a substantially more frequent complication in women than in men.

Regarding the risk factors, in the present study, females had a significantly elevated BMI compared to males. This finding likely stems from biological and sociocultural forces [31], since other studies have found that BMI is more pronounced in females than males (Spain) [32] or that females have a significantly lower BMI than males (Vietnam) [29]. Wang and colleagues, in 2022, explored the relationship between BMI and the risk of stroke in a systematic review and reported a positive association between the risk of stroke and BMI and that the association was stronger in males with AIS [33].

In the current study, females had a significantly higher rate of AF than males, which agrees with previous studies that reported that females had a significantly higher risk for AF-related AIS [16, 29, 34,35,36,37]. AF is associated with double the risk of stroke in females [38], who experienced more severe strokes [39], and increased all-cause mortality in females compared to males [40].

In this study, females had a significantly higher frequency of hypertension compared to males, which agrees with findings reported in previous studies [16, 36, 37, 41]. In addition, other studies from the US and international cohorts demonstrated a stronger association between hypertension and risk of AIS in females compared with males, adjusted for the use of antihypertensives [15,31,, 42, 43]. This finding could be explained by the fact that females are vulnerable to an increased risk of hypertension compared to males stemming from the hypertensive disorders of pregnancy.

Smoking was significantly predominant in males, which is in line with the findings reported by previous studies [29, 41] and is similar to that reported by the ANGEL–ACT prospective large vessel occlusion registry in China [44]. This result could be explained by sociocultural issues related to gender.

Regarding the stroke subtypes and stroke severity at presentation, in the current study, females had a significantly higher frequency of cardioembolic stroke compared to males, which was in accordance with the results from several previous studies [36, 44, 45]. However, Ton and colleagues, in 2023, found no difference between the sexes [29]. The higher frequency of cardioembolic stroke in females can be explained partially by their higher frequency of AF. Moreover, the lower rate of large artery atherosclerosis in females may be related to the absence of tobacco use in females.

Concerning stroke severity at onset, there were no significant sex differences in the stroke severity by the NIHSS scale and mRS on admission. This result agrees with the findings of Ton and colleagues in 2923 [29], who reported no sex differences in stroke severity at admission using the NIHSS scale. This finding could be related to patients receiving r-TPA exclusion criteria, as patients with NIHSS below ≤ 5 and above ≥ 25 were excluded.

Regarding the access to thrombolytic therapy (rTPA), pre-and in-hospital delays, response to thrombolysis, and complications, the current study shows the percentage of females received rTPA was lower than in males; however, we cannot say that females are less likely to receive thrombolysis. This finding could be attributed to the fact that we did not have information on the sex distribution of the initial cohort of patients admitted to each hospital with stroke.

In this study, the onset to needle time was significantly shorter in females than males (p = 0.035), and the door to the needle was significantly shorter in females than males. Our results were in accordance with the findings reported by Ton and colleagues in 2023. They found that females had significantly shorter door-to-needle and door-to-recanalization times [29]. However, the present findings contrast with the results reported by Cai and colleagues in 2020 [46], who stated that the onset-to-door time was not different between sexes, whereas the door-to-needle time was significantly longer in females than males. The current finding demonstrates that in-hospital treatment delays were not different between sexes, but pre-hospital delays were substantially shorter in females, which could be attributed to the fact that our cases are from Upper Egypt, the region in which the male is the predominant figure in the family; therefore, when a female suffers a stroke, there is a rapid response in seeking medical advice, resulting in a shorter time to arrive at the hospital and to receive treatment.

Concerning the complications of rTPA, we found no significant difference between males and females in the intracerebral haemorrhage (ICH) rate after thrombolysis. This result contrasts with the findings by Cai and colleagues in 2020 [46], who reported that ICH was higher in females. However, sex was no longer associated with ICH after adjusting for age, disease severity, and relative pathogenic mechanisms.

Regarding the functional outcomes and mortality and their predictors, there was a significant improvement in the NIHSS in both sexes at 3 months, with no significant difference between them. Our results are consistent with those reported in several previous studies [7, 29, 36, 37], although Cai and colleagues, in 2020, reported that improvement in NIHSS scores was more significant in females than in males [46]. In contrast, Spaander and colleagues 2017 found that females had poorer functional outcomes than males [47]. The variations could be attributed to differences in the study sample sizes.

There were no gender differences in the stroke death rate, consistent with Abdu and Seyoum in 2022 [41]. In contrast to our results, Cai and colleagues in 2020 [46] found that the mortality rate was higher in females than in males after thrombolysis.

Despite longer onset-to-door times in males, the lack of outcome differences suggests a role for sex-based ischemic tolerance factors potentially related to hormone-mediated cytoprotection. However, interpretations are limited, given unaccounted confounders and sample size constraints in subset analysis.

The potential predictors of poor Outcome 3 months after AIS included DM, door-to-needle time, and haemorrhage (DM and door-to-needle time for males; haemorrhage for females). The main potential predictors for mortality were haemorrhage and AF (AF for females; haemorrhage for males). These findings indicate the need for close follow-up of patients with these risk factors, proper rTPA patient selection to avoid haemorrhage risk, and aggressive management for good outcomes. We cannot definitively explain the sex-specific predictors of mortality and poor outcomes identified here. Sample size limitations restrict multivariate adjustment for possible confounders.

This study has several limitations. First, a relatively small sample size may have affected the statistical power and generalizability of the findings. Second, the lack of data on socioeconomic status, education, length of stay, and long-term follow-up precluded a more comprehensive analysis of potential confounding variables. To address these limitations, future studies should employ larger cohorts and collect more comprehensive demographic and longitudinal data to examine long-term sex-specific outcomes and associated factors better.