Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region

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Abstract Background Intracranial aneurysms (IAs) are vascular abnormalities characterized by localized dilation of cerebral arteries, with a higher prevalence in females. Ruptured IAs can lead to subarachnoid hemorrhage, a life-threatening condition. The purpose of this study is to investigate gender-based differences in aneurysm distribution and rupture risk, focusing on the role of anatomical, hemodynamic, and hormonal factors. Results: Among 164 patients, 85 were women (51.83%) and 79 were men (48.17%). The anterior communicating artery (ACA) was the most common site (34.76%), followed by the internal carotid artery (ICA) (30.49%) and middle cerebral artery (MCA) (18.29%). Women had a higher prevalence of ICA aneurysms (25.91% vs. 24.09%), while men showed a greater occurrence in the ACA (27.46% vs. 29.54%). Age-related differences were observed, with women experiencing ruptures at older ages. Conclusions: Gender disparities in IA distribution highlight the influence of anatomical and hormonal factors. Women exhibit a higher prevalence in ICA aneurysms, whereas men are more affected in the ACA. These findings emphasize the need for sex-specific risk assessment, preventive strategies, and tailored clinical management. Future research should focus on predictive modeling for improved early detection and intervention.
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Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region Mohammad Abedalqader Qannas, Abdul Azim Abdul Haffis, Ahmed Abdelkader, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6992239/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Intracranial aneurysms (IAs) are vascular abnormalities characterized by localized dilation of cerebral arteries, with a higher prevalence in females. Ruptured IAs can lead to subarachnoid hemorrhage, a life-threatening condition. The purpose of this study is to investigate gender-based differences in aneurysm distribution and rupture risk, focusing on the role of anatomical, hemodynamic, and hormonal factors. Results: Among 164 patients, 85 were women (51.83%) and 79 were men (48.17%). The anterior communicating artery (ACA) was the most common site (34.76%), followed by the internal carotid artery (ICA) (30.49%) and middle cerebral artery (MCA) (18.29%). Women had a higher prevalence of ICA aneurysms (25.91% vs. 24.09%), while men showed a greater occurrence in the ACA (27.46% vs. 29.54%). Age-related differences were observed, with women experiencing ruptures at older ages. Conclusions: Gender disparities in IA distribution highlight the influence of anatomical and hormonal factors. Women exhibit a higher prevalence in ICA aneurysms, whereas men are more affected in the ACA. These findings emphasize the need for sex-specific risk assessment, preventive strategies, and tailored clinical management. Future research should focus on predictive modeling for improved early detection and intervention. Intracranial aneurysms gender differences rupture risk aneurysm site INTRODUCTION An intracranial aneurysm (IA), also known as a cerebral aneurysm, is a cerebrovascular disorder characterized by a localized dilation or ballooning of a blood vessel in the brain due to a weakness in the vessel wall. IAs can be divided into four main types: saccular, fusiform, dissecting, and mycotic type. The most common type of IA is the saccular and 85% of cases occur in the Circle of Willis. ( 1 , 2 ) When the aneurysm ruptures, it may bleed into the subarachnoid space, leading to a subarachnoid hemorrhage (SAH). Females are approximately three times more likely to have an unruptured IA and are also 1.6 times more prone to aneurysm rupture, which leads to subarachnoid hemorrhage, compared to men. ( 1 – 3 ) The most frequent anatomical predisposition for IA is the anterior communicating artery (35% of the cases), the internal carotid artery (30%—including the carotid artery itself, the posterior communicating artery, and the ophthalmic artery). The middle cerebral artery has a case prevalence of 22%, and finally, the posterior circulation sites, most commonly the basilar artery tip. ( 1 ) The unique characteristics of these arteries suggest the blood flow at these arterial junctions is more turbulent due to abrupt vascular angles or bifurcations with wider angles which inadvertently results in greater shear stress in these areas. These factors induce endothelial cell damage, thinning of the intima media and smooth muscle degeneration which degrade the extracellular matrix giving rise to the formation of an aneurysm. ( 4 ) Risk factors for unruptured intracranial aneurysms include demographics, aneurysm characteristics (size, shape, and location), multiple aneurysms, prior subarachnoid hemorrhage, family history of smoking, and hypertension. These factors also play a critical role in guiding treatment decisions.[ 5 , 6 ] The prevalence of unruptured IAs in women reached 6% while the overall prevalence in the study population was reportedly 3%-4%. Smoking has a greater impact on women than on men and has a relationship with low levels of 15-PGDH which could serve as a pro-oxidative damaging action of smoking in women.[ 7 , 8 ]. Researchers suggest that hormones also play a role in IAs pathogenesis with a decline in the concentration of estrogen in peri- and post-menopause periods leading to structure and function changes in the cerebral artery which favor the formation and rupture of IAs. Estrogens have a mediated protection mechanism towards the first step of IA formation: hemodynamic injury-induced endothelial dysfunction at the intracranial artery bifurcation. [ 7 , 9 – 12 ] Research shows unruptured IAs have a preferred location on the internal carotid artery (ICA) in women (54% vs 38% in men). In contrast, in men, it frequently occurs in the anterior cerebral artery (ACA) (29% vs 15% in women) and anterior communicating artery. This sex-specific distinction may be attributed to the measurement of the diameter of arteries of the circle of Willis revealed that ICA, ACA, posterior cerebral artery and basilar artery were substantially smaller in women than in men, with the most pronounced difference found in ICA. [ 7 , 13 ] Materials and Methods This retrospective, single-institutional cohort study included patients admitted to the High Technology Medical Center, University Clinic, in Tbilisi, Georgia, between January 2022 and December 2024. The study was approved by the High Technology Medical Center's institutional review board, and data were anonymized to maintain patient confidentiality. The study included patients aged 40 to 60 who were diagnosed with intracranial aneurysms and confirmed through imaging techniques. Most importantly, patients consented to the use of their clinical data for research purposes. The study identified patients with intracranial aneurysms using CT angiography (CTA) and Magnetic Resonance Angiography (MRA) as primary diagnostic tools. In certain cases, Digital Subtraction Angiography (DSA) was utilized to verify the diagnosis. Exclusion criteria comprised individuals with inadequate or incomplete documentation. Data collection: Information was extracted retrospectively from electronic health records and imaging databases. The collected variables encompassed patient demographics (age, gender) and aneurysm characteristics (site, rupture status) Data sources and confidentiality: The study period was selected based on the availability of the complete medical records and consistency in diagnosing aneurysms using CTA, MRA, and DSA within the timeframe. Data was extracted from the High Technology Medical Center database, and all data were anonymized using patient record numbers to ensure confidentiality. Statistical analysis: Univariate and multivariate logistic regression analyses were performed to identify gender specific differences associated with intracranial aneurysms. Categorical variables within the study were compared using chi square tests. P-values less than 0.05 were considered to be statistically significant. Outcome measures The main outcome variable assessed was the occurrence of Intracranial Aneurysms, categorized by gender (male, female) and anatomical site (ICA, MCA, AComA), as well as the incidence of ruptured and unruptured aneurysms across both sexes and specific locations. The additional outcome measure evaluated the relationship between aneurysm rupture and patient age (for both sexes) as well as aneurysm location. The rationale for exclusion criteria The study focused on the 40–60 age group as it represented the most consistently available and complete dataset within our institution's medical records, ensuring statistical power and reducing missing data bias. Results The study included a total of 164 patients diagnosed with intracranial aneurysms, with 79 men (48.17%) and 85 women (51.83%). Demographic details, including the distribution of aneurysm sites according to gender is presented in Table 1 . Aneurysm sites varied in prevalence across the study population. The anterior communicating artery (ACA) was the most commonly affected site, comprising 57 cases (34 men, 27.46%; 23 women, 29.54%). This was followed by the internal carotid artery (ICA) with 50 cases, of which a higher proportion was observed in women (34 cases, 25.91%) compared to men (16 cases, 24.09%). Middle cerebral artery (MCA) aneurysms were also notable, with 30 cases reported; these were more frequent in men (19 cases, 14.45%) than in women (11 cases, 15.55%). Aneurysms located in the posterior communicating artery (PCommA) and other sites were less prevalent, collectively contributing to 27 cases (16.47% of total cases). Table 1 Distribution of Aneurysm Sites by Gender Aneurysm Site Total Cases Men (n) Men (%) Women (n) Women (%) Anterior Communicating Artery (ACA) 57 34 27.46 23 29.54 Internal Carotid Artery (ICA) 50 16 24.09 34 25.91 Middle Cerebral Artery (MCA) 30 19 14.45 11 15.55 Posterior Communicating Artery (PCommA) 7 2 3.31 5 3.63 Other Sites 20 8 9.36 12 10.37 Among the 164 aneurysms analyzed, 25 (15.24%) were ruptured, and 139 (84.76%) were unruptured. Rupture status varied by gender, as shown in Table 2 . A slightly higher proportion of ruptures was observed in women (13%) compared to men (12%). Conversely, unruptured aneurysms were more prevalent in both men (67%) and women (72%). The relationship between gender and rupture status was assessed using a chi-square test, revealing a statistically significant association (χ² = 12.62, df = 4, p = 0.013). This suggests gender-based differences in rupture risk within the studied population. Table 2 Rupture Status by Gender Rupture Status Total Cases Men (%) Women (%) Ruptured 25 12 13 Unruptured 139 67 72 Total 164 79 85 The frequency of ruptures varied significantly depending on aneurysm location, as shown in Table 3 . The ACA was associated with the highest number of ruptured aneurysms (13 cases, 8.69%), followed by the MCA and other sites (5 cases each). Ruptures were least common in the PCommA, with only 1 case (1.07%). Unruptured aneurysms were more prevalent across all sites, particularly in the ACA (44 cases, 48.31%) and ICA (49 cases, 42.38%). A chi-square test of independence revealed a significant association between aneurysm site and rupture frequency (χ² = 10.84, df = 4, p = 0.028). This indicates that rupture frequencies differ significantly across aneurysm sites (p < 0.05). Table 3 Rupture Status by Aneurysm Site Aneurysm Site Total Cases Ruptured (n) Ruptured (%) Unruptured (n) Unruptured (%) Anterior Communicating Artery (ACA) 57 13 8.69 44 48.31 Internal Carotid Artery (ICA) 50 1 7.62 49 42.38 Middle Cerebral Artery (MCA) 30 5 4.57 25 25.43 Other Sites 20 5 3.06 15 16.95 Posterior Communicating Artery (PCommA) 7 1 1.07 6 5.93 These findings underscore significant gender and site-specific differences in aneurysm distribution and rupture risk. The ACA exhibited the highest rupture frequency, while the PCommA showed the lowest. Gender disparities in both rupture and unruptured aneurysm prevalence further highlight the need for tailored clinical assessment and management strategies. Discussion Hemodynamic stress is a significant risk factor for intracranial aneurysm (IA) formation, with anatomical variations in the circle of Willis between men and women playing a critical role. Differences in arterial diameters and bifurcation geometry increase hemodynamic forces in women, leading to greater endothelial shear stress and vascular wall remodeling. This elevated stress contributes to endothelial dysfunction, increased inflammatory response, and degradation of the extracellular matrix, promoting IA formation and progression, This aligns with our study, which included 164 patients diagnosed with intracranial aneurysms (IAs). The prevalence of IAs was higher in women (51.83%) compared to men (48.17%) [ 14 ]. 1. Difference in Common Aneurysm Sites Between Men and Women The distribution of aneurysm sites demonstrates distinct gender-based patterns. In this study, men exhibited a higher prevalence of anterior communicating artery (ACA) aneurysms (34 cases) compared to women (23 cases). Conversely, women were more likely to have aneurysms in the internal carotid artery (ICA), with 34 cases versus 16 in men. These findings align with prior research that identifies a significantly higher proportion of ACA aneurysms in men and ICA aneurysms in women (p < 0.001) [ 15 ]. Similarly, it has also been reported that ACA aneurysms accounted for 81% of male cases and only 49% of female cases, while ICA aneurysms were predominant in females (64% vs. 24% in males) [ 16 ]. Additionally, it was stated that women had double the amount of aneurysms in the ICA compared to men[ 17 ]. The physiological basis for these differences may include hormonal effects, such as the vascular protective properties of estrogen, and gender-specific anatomical variations in vessel size and geometry. For example, women’s smaller vessel diameters may predispose them to aneurysms in regions like the ICA, where shear stress and wall tension are more concentrated. Lifestyle factors and comorbidities unique to each gender may also play a role.[ 20 ] 2. Difference in Ruptured vs. Unruptured Aneurysms Between Men and Women Rupture trends further underscore gender distinctions in aneurysm presentation. While both sexes showed a higher prevalence of unruptured aneurysms, women experienced slightly more ruptured aneurysms (13 cases) compared to men (12 cases). Notably, ruptured aneurysms in women were predominantly located at the ICA (42%), consistent with Watt et al. (2020), who observed a higher frequency of ICA ruptures in females [ 17 ]. In contrast, ruptured ACA aneurysms were more common in men (47%), reflecting findings by Ghods et al [ 15 ]. Women’s heightened rupture risk may stem from hormonal changes post-menopause and lower aneurysm size thresholds for rupture. Additionally, women were more likely to present with multiple aneurysms, which occurred in 11% of female cases compared to 6% in males [ 18 ]. The average age of rupture differed between genders, with men presenting at 53 years and women at 59 years. These findings are consistent with the results of Park et al. (2008), who attributed the younger age of rupture in men to lifestyle factors such as smoking and hypertension. [ 19 ] 3. Aneurysm Site and Rupture Likelihood The risk of rupture was strongly associated with the aneurysm site. ACA aneurysms exhibited the highest rupture frequency (22.8%), followed by MCA aneurysms (16.7%). ICA aneurysms, despite their prevalence in women, demonstrated a notably low rupture rate (2.0%). These findings reinforce the conclusions of Kongable et al. (1996), who identified site-specific hemodynamic stress and vascular wall structure as critical determinants of rupture risk. [ 12 ] This study’s chi-square analysis (p = 0.028) confirmed a statistically significant relationship between aneurysm location and rupture likelihood [ 20 ]. The higher rupture risk in ACA aneurysms may be due to their exposure to complex hemodynamic forces at bifurcation points, whereas ICA aneurysms may benefit from more stable flow patterns. Implications for Clinical Practice These findings underscore the necessity of site-specific management solutions. ACA aneurysms, given their higher rupture potential, warrant more frequent monitoring and earlier intervention in both men and women. For women, especially postmenopausal women, ICA aneurysms may require tailored surveillance protocols to address their unique distribution and rupture characteristics. Future research should focus on integrating hormonal, anatomical, and hemodynamic factors into predictive models to improve patient outcomes. Conclusion This study serves to highlight the gender-based differences in various aspects of aneurysms, especially regarding aneurysm location and frequency of rupture. Women had a higher prevalence of aneurysms in the ICA, whereas men had more frequent aneurysms in the ACA. These differences extend to aneurysm rupture rates as well, with women having higher rupture tendency, especially in the ICA aneurysms. Meanwhile, men exhibit more ruptured ACA aneurysms. These distinctions could be attributed to a combination of hemodynamic, anatomical, and hormonal factors; so there's a need for personalized treatment and monitoring strategies. The association between aneurysm site and rupture risk underscores the importance of targeted surveillance, especially for ACA aneurysms, which showed the highest rupture frequency. The study also highlights the role of age; women experience ruptures at older ages than men on average, suggesting the role of hormonal changes post-menopause. Further research on the subject is required to formulate predictive models to improve the diagnosis and management of IAs. By taking these gender differences into account, clinicians can formulate better algorithms to optimize patient care and minimize risks. Declarations Future Research Suggestions More investigating on the impact of hormones and hormonal changes, on aneurysm formation and rupture risk would add depth to our understanding of gender differences in aneurysm pathophysiology. Future research should look into how differences in vascular anatomy, such as arterial width and branching patterns, affect gender-specific aneurysm distribution and rupture rates. Consent for publication: Informed consent was obtained from all patients. Availability of data and materials: All the variables that were used in this study are available. Ethics approval and consent to participate The ethical approval was obtained from the High Technology Medical Center University Clinic with number:03-7/O-1 We have anonymized the patient information that could identify an individual. Limitations This study has several limitations. First, it was conducted at a single medical center, which may limit the generalizability of the findings to broader populations. Second, the sample size, although adequate for exploratory analysis, was relatively small, particularly in subgroup comparisons of rupture status across aneurysm sites and genders. This limits the statistical power to detect more subtle associations. Additionally, the retrospective design may carry the risk of missing or incomplete data, although efforts were made to minimize this through rigorous chart review and inclusion criteria. However, this study represents the first dataset from Georgia—and more broadly, the entire Caucasus region—to examine gender-based patterns in intracranial aneurysm distribution and rupture risk. This regional uniqueness adds valuable insight to the global literature and provides a foundation for future multicenter research in underrepresented populations Competing interests: There are none. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Authors' contributions AQ and AA, the team leader, was instructing the subteams and was reviewing and editing their work. Dr. EE was the supervisor and the source of the data. TT, under the supervision of Dr. EE and the ethical committee, translated the data from Georgian to English. ASJ, CP and MA wrote the introduction. JG and AH wrote the methodology. GG has worked on the results. RS and NM and AZ wrote the discussion. RGR is the author of the conclusion and abstract. References Keedy A. An overview of intracranial aneurysms. McGill J Med. 2006;9(2):141–6. PMID: 18523626; PMCID: PMC2323531. Gasparotti R, Liserre R. Intracranial aneurysms. 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Differences in anatomical distribution, gender, and sidedness between ruptured and unruptured intracranial aneurysms in a defined patient population. Acta Neurochir (Wien) [Internet]. 2009;151(12):1569–74. Available from: https://doi.org/10.1007/s00701-009-0316-3 Watt J, Watt C, Van Schoor A. A gender-based comparative aneurysm study regarding age at presentation, location, and possible causative factors. Anatol J Fam Med. 2020;3(3):211–5. Hariri E, Matta M, Layoun H, Badwan O, Braghieri L, Owens III AP et al. Antiplatelet therapy, abdominal aortic aneurysm progression, and clinical outcomes. JAMA Network Open [Internet]. 2023;6(12):e2347296. Available from: https://doi.org/10.1001/jamanetworkopen.2023.47296 Park SK, Kim JM, Kim JH, Cheong JH, Bak KH, Kim CH. Aneurysmal subarachnoid hemorrhage in young adults: A gender comparison study. J Clin Neurosci [Internet]. 2008;15:389–92. Available from: https://doi.org/10.1016/j.jocn.2007.04.007 Kongable GL, Lanzino G, Germanson TP, Truskowski LL, Alves WM, Torner JC et al. Gender-related differences in aneurysmal subarachnoid hemorrhage. J Neurosurg [Internet]. 1996;84:43–8. Available from: https://doi.org/10.3171/jns.1996.84.1.0043 Klis KM, Kucala R, Polak J, Kwinta BM, Starowicz-Filip A, Stachura K, et al. Intracranial aneurysm distribution and characteristics according to gender. Br J Neurosurg [Internet]. 2018. Available from: https://doi.org/10.1080/02688697.2018.1518514 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Sep, 2025 Reviews received at journal 09 Sep, 2025 Reviewers agreed at journal 26 Aug, 2025 Reviews received at journal 12 Jul, 2025 Reviewers agreed at journal 12 Jul, 2025 Reviewers invited by journal 07 Jul, 2025 Editor assigned by journal 30 Jun, 2025 Submission checks completed at journal 30 Jun, 2025 First submitted to journal 27 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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SEU","correspondingAuthor":false,"prefix":"","firstName":"Rajvi","middleName":"","lastName":"Soni","suffix":""},{"id":481569745,"identity":"b239c56f-f64d-4d39-ba30-95dc413e3d71","order_by":10,"name":"Nazia Mohammad","email":"","orcid":"","institution":"Ivane Javakhishvili tbilisi state university","correspondingAuthor":false,"prefix":"","firstName":"Nazia","middleName":"","lastName":"Mohammad","suffix":""},{"id":481569747,"identity":"cbb781f3-729b-43cf-b01e-9ffcfc147996","order_by":11,"name":"Ahmad Hammoud","email":"","orcid":"","institution":"Ilia State University","correspondingAuthor":false,"prefix":"","firstName":"Ahmad","middleName":"","lastName":"Hammoud","suffix":""},{"id":481569748,"identity":"f314eb30-8d0e-4054-b9f7-839e2a8e907f","order_by":12,"name":"Ryan George Rajeev","email":"","orcid":"","institution":"David Tvildiani Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ryan","middleName":"George","lastName":"Rajeev","suffix":""},{"id":481569749,"identity":"f96144ed-d221-46ce-8f4a-429c2668d64e","order_by":13,"name":"Chetali Patil","email":"","orcid":"","institution":"NewVision University","correspondingAuthor":false,"prefix":"","firstName":"Chetali","middleName":"","lastName":"Patil","suffix":""}],"badges":[],"createdAt":"2025-06-27 13:53:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6992239/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6992239/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86449065,"identity":"363da1ad-b44a-4c8b-b9aa-0a6953216de7","added_by":"auto","created_at":"2025-07-10 18:37:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":757941,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6992239/v1/3afd2fde-7a39-4158-9794-82a5108fea1f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAn intracranial aneurysm (IA), also known as a cerebral aneurysm, is a cerebrovascular disorder characterized by a localized dilation or ballooning of a blood vessel in the brain due to a weakness in the vessel wall. IAs can be divided into four main types: saccular, fusiform, dissecting, and mycotic type. The most common type of IA is the saccular and 85% of cases occur in the Circle of Willis. (\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e) When the aneurysm ruptures, it may bleed into the subarachnoid space, leading to a subarachnoid hemorrhage (SAH). Females are approximately three times more likely to have an unruptured IA and are also 1.6 times more prone to aneurysm rupture, which leads to subarachnoid hemorrhage, compared to men. (\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e)\u003c/p\u003e\u003cp\u003eThe most frequent anatomical predisposition for IA is the anterior communicating artery (35% of the cases), the internal carotid artery (30%\u0026mdash;including the carotid artery itself, the posterior communicating artery, and the ophthalmic artery). The middle cerebral artery has a case prevalence of 22%, and finally, the posterior circulation sites, most commonly the basilar artery tip. (\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e) The unique characteristics of these arteries suggest the blood flow at these arterial junctions is more turbulent due to abrupt vascular angles or bifurcations with wider angles which inadvertently results in greater shear stress in these areas. These factors induce endothelial cell damage, thinning of the intima media and smooth muscle degeneration which degrade the extracellular matrix giving rise to the formation of an aneurysm. (\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e)\u003c/p\u003e\u003cp\u003eRisk factors for unruptured intracranial aneurysms include demographics, aneurysm characteristics (size, shape, and location), multiple aneurysms, prior subarachnoid hemorrhage, family history of smoking, and hypertension. These factors also play a critical role in guiding treatment decisions.[\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e] The prevalence of unruptured IAs in women reached 6% while the overall prevalence in the study population was reportedly 3%-4%. Smoking has a greater impact on women than on men and has a relationship with low levels of 15-PGDH which could serve as a pro-oxidative damaging action of smoking in women.[\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e].\u003c/p\u003e\u003cp\u003eResearchers suggest that hormones also play a role in IAs pathogenesis with a decline in the concentration of estrogen in peri- and post-menopause periods leading to structure and function changes in the cerebral artery which favor the formation and rupture of IAs. Estrogens have a mediated protection mechanism towards the first step of IA formation: hemodynamic injury-induced endothelial dysfunction at the intracranial artery bifurcation. [\u003csup\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/span\u003e,\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e\u003cp\u003eResearch shows unruptured IAs have a preferred location on the internal carotid artery (ICA) in women (54% vs 38% in men). In contrast, in men, it frequently occurs in the anterior cerebral artery (ACA) (29% vs 15% in women) and anterior communicating artery. This sex-specific distinction may be attributed to the measurement of the diameter of arteries of the circle of Willis revealed that ICA, ACA, posterior cerebral artery and basilar artery were substantially smaller in women than in men, with the most pronounced difference found in ICA. [\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis retrospective, single-institutional cohort study included patients admitted to the High Technology Medical Center, University Clinic, in Tbilisi, Georgia, between January 2022 and December 2024. The study was approved by the High Technology Medical Center's institutional review board, and data were anonymized to maintain patient confidentiality.\u003c/p\u003e\u003cp\u003eThe study included patients aged 40 to 60 who were diagnosed with intracranial aneurysms and confirmed through imaging techniques. Most importantly, patients consented to the use of their clinical data for research purposes. The study identified patients with intracranial aneurysms using CT angiography (CTA) and Magnetic Resonance Angiography (MRA) as primary diagnostic tools. In certain cases, Digital Subtraction Angiography (DSA) was utilized to verify the diagnosis.\u003c/p\u003e\u003cp\u003eExclusion criteria comprised individuals with inadequate or incomplete documentation.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData collection:\u003c/h2\u003e\u003cp\u003eInformation was extracted retrospectively from electronic health records and imaging databases. The collected variables encompassed patient demographics (age, gender) and aneurysm characteristics (site, rupture status)\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData sources and confidentiality:\u003c/h3\u003e\n\u003cp\u003eThe study period was selected based on the availability of the complete medical records and consistency in diagnosing aneurysms using CTA, MRA, and DSA within the timeframe. Data was extracted from the High Technology Medical Center database, and all data were anonymized using patient record numbers to ensure confidentiality.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis:\u003c/h2\u003e\u003cp\u003eUnivariate and multivariate logistic regression analyses were performed to identify gender specific differences associated with intracranial aneurysms. Categorical variables within the study were compared using chi square tests. P-values less than 0.05 were considered to be statistically significant.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eOutcome measures\u003c/h3\u003e\n\u003cp\u003eThe main outcome variable assessed was the occurrence of Intracranial Aneurysms, categorized by gender (male, female) and anatomical site (ICA, MCA, AComA), as well as the incidence of ruptured and unruptured aneurysms across both sexes and specific locations. The additional outcome measure evaluated the relationship between aneurysm rupture and patient age (for both sexes) as well as aneurysm location.\u003c/p\u003e\n\u003ch3\u003eThe rationale for exclusion criteria\u003c/h3\u003e\n\u003cp\u003eThe study focused on the 40\u0026ndash;60 age group as it represented the most consistently available and complete dataset within our institution's medical records, ensuring statistical power and reducing missing data bias.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included a total of 164 patients diagnosed with intracranial aneurysms, with 79 men (48.17%) and 85 women (51.83%). Demographic details, including the distribution of aneurysm sites according to gender is presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Aneurysm sites varied in prevalence across the study population. The anterior communicating artery (ACA) was the most commonly affected site, comprising 57 cases (34 men, 27.46%; 23 women, 29.54%). This was followed by the internal carotid artery (ICA) with 50 cases, of which a higher proportion was observed in women (34 cases, 25.91%) compared to men (16 cases, 24.09%). Middle cerebral artery (MCA) aneurysms were also notable, with 30 cases reported; these were more frequent in men (19 cases, 14.45%) than in women (11 cases, 15.55%). Aneurysms located in the posterior communicating artery (PCommA) and other sites were less prevalent, collectively contributing to 27 cases (16.47% of total cases).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistribution of Aneurysm Sites by Gender\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAneurysm Site\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal Cases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMen (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMen (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eWomen (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eWomen (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnterior Communicating Artery (ACA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e27.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e29.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternal Carotid Artery (ICA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e25.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMiddle Cerebral Artery (MCA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e15.55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePosterior Communicating Artery (PCommA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3.63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther Sites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e10.37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAmong the 164 aneurysms analyzed, 25 (15.24%) were ruptured, and 139 (84.76%) were unruptured. Rupture status varied by gender, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. A slightly higher proportion of ruptures was observed in women (13%) compared to men (12%). Conversely, unruptured aneurysms were more prevalent in both men (67%) and women (72%). The relationship between gender and rupture status was assessed using a chi-square test, revealing a statistically significant association (χ\u0026sup2; = 12.62, df\u0026thinsp;=\u0026thinsp;4, p\u0026thinsp;=\u0026thinsp;0.013). This suggests gender-based differences in rupture risk within the studied population.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRupture Status by Gender\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRupture Status\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal Cases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMen (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWomen (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRuptured\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnruptured\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e72\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e164\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe frequency of ruptures varied significantly depending on aneurysm location, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The ACA was associated with the highest number of ruptured aneurysms (13 cases, 8.69%), followed by the MCA and other sites (5 cases each). Ruptures were least common in the PCommA, with only 1 case (1.07%). Unruptured aneurysms were more prevalent across all sites, particularly in the ACA (44 cases, 48.31%) and ICA (49 cases, 42.38%). A chi-square test of independence revealed a significant association between aneurysm site and rupture frequency (χ\u0026sup2; = 10.84, df\u0026thinsp;=\u0026thinsp;4, p\u0026thinsp;=\u0026thinsp;0.028). This indicates that rupture frequencies differ significantly across aneurysm sites (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRupture Status by Aneurysm Site\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAneurysm Site\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal Cases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRuptured (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRuptured (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eUnruptured (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eUnruptured (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnterior Communicating Artery (ACA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e48.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternal Carotid Artery (ICA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e42.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMiddle Cerebral Artery (MCA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e25.43\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther Sites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e16.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePosterior Communicating Artery (PCommA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e5.93\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThese findings underscore significant gender and site-specific differences in aneurysm distribution and rupture risk. The ACA exhibited the highest rupture frequency, while the PCommA showed the lowest. Gender disparities in both rupture and unruptured aneurysm prevalence further highlight the need for tailored clinical assessment and management strategies.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHemodynamic stress is a significant risk factor for intracranial aneurysm (IA) formation, with anatomical variations in the circle of Willis between men and women playing a critical role. Differences in arterial diameters and bifurcation geometry increase hemodynamic forces in women, leading to greater endothelial shear stress and vascular wall remodeling. This elevated stress contributes to endothelial dysfunction, increased inflammatory response, and degradation of the extracellular matrix, promoting IA formation and progression, This aligns with our study, which included 164 patients diagnosed with intracranial aneurysms (IAs). The prevalence of IAs was higher in women (51.83%) compared to men (48.17%) [\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e14\u003c/span\u003e ].\u003c/p\u003e\n\u003ch3\u003e1. Difference in Common Aneurysm Sites Between Men and Women\u003c/h3\u003e\n\u003cp\u003eThe distribution of aneurysm sites demonstrates distinct gender-based patterns. In this study, men exhibited a higher prevalence of anterior communicating artery (ACA) aneurysms (34 cases) compared to women (23 cases). Conversely, women were more likely to have aneurysms in the internal carotid artery (ICA), with 34 cases versus 16 in men. These findings align with prior research that identifies a significantly higher proportion of ACA aneurysms in men and ICA aneurysms in women (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) [\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e]. Similarly, it has also been reported that ACA aneurysms accounted for 81% of male cases and only 49% of female cases, while ICA aneurysms were predominant in females (64% vs. 24% in males) [\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e]. Additionally, it was stated that women had \u003cem\u003edouble\u003c/em\u003e the amount of aneurysms in the ICA compared to men[\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e].\u003c/p\u003e\u003cp\u003eThe physiological basis for these differences may include hormonal effects, such as the vascular protective properties of estrogen, and gender-specific anatomical variations in vessel size and geometry. For example, women\u0026rsquo;s smaller vessel diameters may predispose them to aneurysms in regions like the ICA, where shear stress and wall tension are more concentrated. Lifestyle factors and comorbidities unique to each gender may also play a role.[\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e2. Difference in Ruptured vs. Unruptured Aneurysms Between Men and Women\u003c/h2\u003e\u003cp\u003eRupture trends further underscore gender distinctions in aneurysm presentation. While both sexes showed a higher prevalence of unruptured aneurysms, women experienced slightly more ruptured aneurysms (13 cases) compared to men (12 cases). Notably, ruptured aneurysms in women were predominantly located at the ICA (42%), consistent with Watt et al. (2020), who observed a higher frequency of ICA ruptures in females [\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e]. In contrast, ruptured ACA aneurysms were more common in men (47%), reflecting findings by Ghods et al [\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e].\u003c/p\u003e\u003cp\u003eWomen\u0026rsquo;s heightened rupture risk may stem from hormonal changes post-menopause and lower aneurysm size thresholds for rupture. Additionally, women were more likely to present with multiple aneurysms, which occurred in 11% of female cases compared to 6% in males [\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e].\u003c/p\u003e\u003cp\u003eThe average age of rupture differed between genders, with men presenting at 53 years and women at 59 years. These findings are consistent with the results of Park et al. (2008), who attributed the younger age of rupture in men to lifestyle factors such as smoking and hypertension. [\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3. Aneurysm Site and Rupture Likelihood\u003c/h2\u003e\u003cp\u003eThe risk of rupture was strongly associated with the aneurysm site. ACA aneurysms exhibited the highest rupture frequency (22.8%), followed by MCA aneurysms (16.7%). ICA aneurysms, despite their prevalence in women, demonstrated a notably low rupture rate (2.0%). These findings reinforce the conclusions of Kongable et al. (1996), who identified site-specific hemodynamic stress and vascular wall structure as critical determinants of rupture risk. [\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e\u003cp\u003eThis study\u0026rsquo;s chi-square analysis (p\u0026thinsp;=\u0026thinsp;0.028) confirmed a statistically significant relationship between aneurysm location and rupture likelihood [\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e]. The higher rupture risk in ACA aneurysms may be due to their exposure to complex hemodynamic forces at bifurcation points, whereas ICA aneurysms may benefit from more stable flow patterns.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eImplications for Clinical Practice\u003c/h2\u003e\u003cp\u003eThese findings underscore the necessity of site-specific management solutions. ACA aneurysms, given their higher rupture potential, warrant more frequent monitoring and earlier intervention in both men and women. For women, especially postmenopausal women, ICA aneurysms may require tailored surveillance protocols to address their unique distribution and rupture characteristics. Future research should focus on integrating hormonal, anatomical, and hemodynamic factors into predictive models to improve patient outcomes.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study serves to highlight the gender-based differences in various aspects of aneurysms, especially regarding aneurysm location and frequency of rupture. Women had a higher prevalence of aneurysms in the ICA, whereas men had more frequent aneurysms in the ACA. These differences extend to aneurysm rupture rates as well, with women having higher rupture tendency, especially in the ICA aneurysms. Meanwhile, men exhibit more ruptured ACA aneurysms.\u003c/p\u003e\u003cp\u003eThese distinctions could be attributed to a combination of hemodynamic, anatomical, and hormonal factors; so there's a need for personalized treatment and monitoring strategies. The association between aneurysm site and rupture risk underscores the importance of targeted surveillance, especially for ACA aneurysms, which showed the highest rupture frequency. The study also highlights the role of age; women experience ruptures at older ages than men on average, suggesting the role of hormonal changes post-menopause.\u003c/p\u003e\u003cp\u003eFurther research on the subject is required to formulate predictive models to improve the diagnosis and management of IAs. By taking these gender differences into account, clinicians can formulate better algorithms to optimize patient care and minimize risks.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFuture Research Suggestions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMore investigating on \u0026nbsp;the impact of hormones and hormonal changes, \u0026nbsp;on aneurysm formation and rupture risk would add depth to our understanding of gender differences in aneurysm pathophysiology.\u003c/p\u003e\n\u003cp\u003eFuture research should look into how differences in vascular anatomy, such as arterial width and branching patterns, affect gender-specific aneurysm distribution and rupture rates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eAll the variables that were used in this study are available.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/h4\u003e\n\u003cp\u003eThe ethical approval was obtained from the High Technology Medical Center University Clinic with number:03-7/O-1\u0026nbsp;We have anonymized the patient information that could identify an individual.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, it was conducted at a single medical center, which may limit the generalizability of the findings to broader populations. Second, the sample size, although adequate for exploratory analysis, was relatively small, particularly in subgroup comparisons of rupture status across aneurysm sites and genders. This limits the statistical power to detect more subtle associations. Additionally, the retrospective design may carry the risk of missing or incomplete data, although efforts were made to minimize this through rigorous chart review and inclusion criteria.\u003c/p\u003e\n\u003cp\u003eHowever, this study represents the first dataset from Georgia—and more broadly, the entire Caucasus region—to examine gender-based patterns in intracranial aneurysm distribution and rupture risk. This regional uniqueness adds valuable insight to the global literature and provides a foundation for future multicenter research in underrepresented populations\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThere are none.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eAQ and AA, the team leader, was instructing the subteams and was reviewing and editing their work.\u003c/li\u003e\n \u003cli\u003eDr. EE was the supervisor and the source of the data.\u003c/li\u003e\n \u003cli\u003eTT, under the supervision of Dr. EE and the ethical committee, translated the data from Georgian to English.\u003c/li\u003e\n \u003cli\u003eASJ,\u0026nbsp;CP and MA wrote the introduction.\u003c/li\u003e\n \u003cli\u003eJG and AH wrote the methodology.\u003c/li\u003e\n \u003cli\u003eGG has worked on the results.\u003c/li\u003e\n \u003cli\u003eRS and NM and AZ wrote the discussion.\u003c/li\u003e\n \u003cli\u003eRGR is the author of the conclusion and abstract.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKeedy A. 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Intracranial aneurysm distribution and characteristics according to gender. Br J Neurosurg [Internet]. 2018. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/02688697.2018.1518514\u003c/span\u003e\u003cspan address=\"10.1080/02688697.2018.1518514\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"artery-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Artery Research](https://arteryresearch.biomedcentral.com/)","snPcode":"44200","submissionUrl":"https://submission.springernature.com/new-submission/44200/3","title":"Artery Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Intracranial aneurysms, gender differences, rupture risk, aneurysm site","lastPublishedDoi":"10.21203/rs.3.rs-6992239/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6992239/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eIntracranial aneurysms (IAs) are vascular abnormalities characterized by localized dilation of cerebral arteries, with a higher prevalence in females. Ruptured IAs can lead to subarachnoid hemorrhage, a life-threatening condition. The purpose of this study is to investigate gender-based differences in aneurysm distribution and rupture risk, focusing on the role of anatomical, hemodynamic, and hormonal factors.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eAmong 164 patients, 85 were women (51.83%) and 79 were men (48.17%). The anterior communicating artery (ACA) was the most common site (34.76%), followed by the internal carotid artery (ICA) (30.49%) and middle cerebral artery (MCA) (18.29%). Women had a higher prevalence of ICA aneurysms (25.91% vs. 24.09%), while men showed a greater occurrence in the ACA (27.46% vs. 29.54%). Age-related differences were observed, with women experiencing ruptures at older ages.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e\u003cp\u003eGender disparities in IA distribution highlight the influence of anatomical and hormonal factors. Women exhibit a higher prevalence in ICA aneurysms, whereas men are more affected in the ACA. These findings emphasize the need for sex-specific risk assessment, preventive strategies, and tailored clinical management. Future research should focus on predictive modeling for improved early detection and intervention.\u003c/p\u003e","manuscriptTitle":"Gender-Based Patterns in Intracranial Aneurysm Site and Rupture Risk: A Single-Center Retrospective Cohort Study from the Caucasus region","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-10 18:13:10","doi":"10.21203/rs.3.rs-6992239/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-09T09:28:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-09T08:22:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"27680500596667418337348368892686273014","date":"2025-08-27T00:49:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-12T14:09:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"115354807361523242507362980487181516227","date":"2025-07-12T12:34:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-07T07:28:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-30T23:42:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-30T23:40:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"Artery Research","date":"2025-06-27T13:42:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"artery-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Artery Research](https://arteryresearch.biomedcentral.com/)","snPcode":"44200","submissionUrl":"https://submission.springernature.com/new-submission/44200/3","title":"Artery Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3a62173a-6e2b-40ba-945d-580c7dc489bf","owner":[],"postedDate":"July 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-18T10:08:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-10 18:13:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6992239","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6992239","identity":"rs-6992239","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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