{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:17:12Z","timestamp":1773829032873,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Sexual dysfunction (SD) is a common yet underrecognized consequence of multiple sclerosis (MS) with multidimensional determinants spanning neurological, physical, and psychosocial domains. However, the relative and incremental contribution of fatigue compared with disability and psychological factors remains insufficiently clarified. This study aimed to evaluate the prevalence and severity of sexual dysfunction in MS and to identify independent and incremental predictors using a hierarchical analytical framework. Methods: In this cross-sectional case\u2013control study, 140 patients with MS and 140 age- and sex-matched healthy controls were assessed. Sexual functioning was evaluated using the Arizona Sexual Experience Scale (ASEX) and the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19). Fatigue severity, anxiety, depression, body image, self-esteem, disability (EDSS), and quality of life were measured using validated instruments. Hierarchical multiple linear regression analyses were conducted within the MS cohort to determine independent predictors of MSISQ-19 domain and total scores and to evaluate the incremental contribution of fatigue. Results: Sexual dysfunction was significantly more prevalent in the MS group compared with controls (70.7% vs. 13.6%, p &lt; 0.001). Patients with MS demonstrated higher fatigue, anxiety, depression, and poorer body image, self-esteem, and quality of life (all p &lt; 0.001). Within the MS cohort, individuals with sexual dysfunction exhibited greater symptom burden and disability. Hierarchical regression analyses showed that fatigue produced the largest increase in explained variance across all MSISQ-19 domains (\u0394R2 range: 0.11\u20130.19) and remained the strongest independent predictor (\u03b2 range: 0.29\u20130.42; p \u2264 0.001). Anxiety retained independent associations with selected domains, whereas disability indices did not remain independently significant after adjustment. Conclusions: Sexual dysfunction in MS reflects a multidimensional burden extending beyond neurological impairment. Fatigue demonstrated the most consistent associations across sexual dysfunction domains, with anxiety contributing to selected aspects of functioning. Given the cross-sectional design, these findings should be interpreted as associations rather than causal relationships. Multidimensional assessment incorporating fatigue and psychological factors may improve the identification of clinically relevant and potentially modifiable determinants within comprehensive MS care.<\/jats:p>","DOI":"10.3390\/jcm15062304","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:35:08Z","timestamp":1773819308000},"page":"2304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional Determinants of Sexual Dysfunction in Multiple Sclerosis: Incremental Insights from a Hierarchical Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Yusuf","family":"Sar\u0131","sequence":"first","affiliation":[{"name":"Department of Psychiatry, \u0130n\u00f6n\u00fc University, Turgut \u00d6zal Medical Center, Malatya 44100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neslihan","family":"Cansel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, \u0130n\u00f6n\u00fc University, Turgut \u00d6zal Medical Center, Malatya 44100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Tecellio\u011flu","sequence":"additional","affiliation":[{"name":"Department of Neurology, \u0130n\u00f6n\u00fc University, Turgut \u00d6zal Medical Center, Malatya 44100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41392-025-02415-4","article-title":"Multiple sclerosis: Molecular pathogenesis and therapeutic intervention","volume":"10","author":"Eixarch","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alluqmani, M. (2025). Multiple Sclerosis: A Comprehensive Spectrum of Symptoms Beyond Motor Dysfunction. Clin. Transl. Neurosci., 9.","DOI":"10.3390\/ctn9010019"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7372789","DOI":"10.1155\/2024\/7372789","article-title":"Multiple sclerosis: An overview of epidemiology, risk factors, and serological biomarkers","volume":"2024","author":"Shi","year":"2024","journal-title":"Acta Neurol. Scand."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70039","DOI":"10.1002\/npr2.70039","article-title":"Primary progressive multiple sclerosis: New therapeutic approaches","volume":"45","author":"Rajabi","year":"2025","journal-title":"Neuropsychopharmacol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rosso, R., Virgilio, E., Bronzini, M., Rolla, S., Maglione, A., and Clerico, M. (2026). The Hidden Players in Multiple Sclerosis Nutrition: A Narrative Review on the Influence of Vitamins, Polyphenols, Salt, and Essential Metals on Disease and Gut Microbiota. Nutrients, 18.","DOI":"10.3390\/nu18010148"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Totuk, O., T\u00fcrkkol, M., Yadi, F., G\u00fcdek, H.C., Erci, G.\u00c7., Do\u011fan, \u0130.G., Tezer, D.\u00c7., Sahin, S., and Demir, S. (2025). Sexual dysfunction in multiple sclerosis: Prevalence, risk factors, and impact on quality of life in a large cohort study. BMC Neurol., 25.","DOI":"10.1186\/s12883-025-04492-y"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yazdani, A., Ebrahimi, N., Mirmosayyeb, O., and Ghajarzadeh, M. (2023). Prevalence and risk of developing sexual dysfunction in women with multiple sclerosis (MS): A systematic review and meta-analysis. BMC Women\u2019s Health, 23.","DOI":"10.1186\/s12905-023-02501-1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.beth.2012.11.002","article-title":"Evaluation of the unique and specific contributions of dimensions of the triple vulnerability model to the prediction of DSM-IV anxiety and mood disorder constructs","volume":"44","author":"Brown","year":"2013","journal-title":"Behav. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1080\/09638288.2023.2237403","article-title":"Development of an integrated conceptual model of multiple sclerosis spasticity","volume":"46","author":"Cameron","year":"2024","journal-title":"Disabil. Rehabil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10865-010-9266-8","article-title":"Fatigue and physical disability in patients with multiple sclerosis: A structural equation modeling approach","volume":"33","author":"Bol","year":"2010","journal-title":"J. Behav. Med."},{"key":"ref_11","first-page":"32","article-title":"Multiple Sclerosis-related Fatigue: An Updated Review of Pathophysiology and Associated Variables Contributing Factors","volume":"5","author":"Yeni","year":"2025","journal-title":"J. Mult. Scler. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1612242025","DOI":"10.1523\/JNEUROSCI.1612-24.2025","article-title":"The Neurobiology of Cognitive Fatigue and Its Influence on Effort-Based Choice","volume":"45","author":"Steward","year":"2025","journal-title":"J. Neurosci."},{"key":"ref_13","first-page":"1151","article-title":"Sex-specific clinical and neurobiological correlates of fatigue in older adults","volume":"47","author":"Alfano","year":"2025","journal-title":"GeroScience"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1080\/09638288.2025.2527959","article-title":"Body image, sexual dysfunction and psychological distress in people with multiple sclerosis","volume":"48","author":"Breheny","year":"2026","journal-title":"Disabil. Rehabil."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.7224\/1537-2073.2018-066","article-title":"Prevalence and Correlates of Body Image Dissatisfaction in Patients with Multiple Sclerosis","volume":"21","author":"Stevens","year":"2019","journal-title":"Int. J. MS Care"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Poli, S., Donisi, V., das Nair, R., Mazzi, M.A., Gajofatto, A., and Rimondini, M. (2025). Psychosocial Correlates of Fatigue in Young Adults with Multiple Sclerosis: Exploring the Roles of Resilience, Mindfulness, and Illness Perception. Healthcare, 13.","DOI":"10.3390\/healthcare13182335"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Scandurra, C., Rosa, L., Carotenuto, A., Moccia, M., Arena, S., Ianniello, A., Nozzolillo, A., Turrini, M., Streito, L.M., and Abbadessa, G. (2023). Sexual dysfunction in people with multiple sclerosis: The role of disease severity, illness perception, and depression. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062215"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mozhdehipanah, H., Sharifi, N., Emami, A., Abbaslou, M.A., and Mirzadeh, M. (2025). The prevalence of sexual dysfunction and its contributors among the women with multiple sclerosis. BMC Women\u2019s Health, 25.","DOI":"10.1186\/s12905-025-03653-y"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/sj.ijir.3901249","article-title":"The reliability and validity of Arizona sexual experiences scale in Turkish ESRD patients undergoing hemodialysis","volume":"16","author":"Soykan","year":"2004","journal-title":"Int. J. Impot. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1111\/jsm.12531","article-title":"The multiple sclerosis intimacy and sexuality questionnaire-19: Reliability, validity, and factor structure of the Persian version","volume":"11","author":"Mohammadi","year":"2014","journal-title":"J. Sex. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jns.2005.09.009","article-title":"Cross-cultural adaptation and validation of multiple sclerosis quality of life questionnaire (MSQOL-54) in a Turkish multiple sclerosis sample","volume":"240","author":"Idiman","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00296-010-1558-3","article-title":"Validation of the Turkish version of the fatigue severity scale in patients with fibromyalgia","volume":"32","author":"Can","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_23","first-page":"51","article-title":"Adaptation of the short-form of state self-esteem scale into Turkish: A study of validity and reliability","volume":"58","author":"Kurnaz","year":"2025","journal-title":"Ank. Univ. J. Fac. Educ. Sci. (JFES)"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"141","DOI":"10.5455\/bcp.20141214105009","article-title":"The reliability and validity of the Turkish version of the Beck Scale for Suicide Ideation (Turkish BSSI)","volume":"25","author":"Ozcelik","year":"2015","journal-title":"Klin. Psikofarmakol. B\u00fclteni-Bull. Clin. Psychopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104907","DOI":"10.1016\/j.msard.2023.104907","article-title":"Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors","volume":"78","author":"Petracca","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"C\u00f3rdoba-Pel\u00e1ez, M.M., Molina-Torres, G., Rutkowska, A., Rutkowski, S., and Rubio-Arias, J.\u00c1. (2025). Analysis of the Structural Characteristics and Psychometric Properties of the Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-15): A Systematic Review and Meta-Analysis. Diagnostics, 15.","DOI":"10.3390\/diagnostics15222836"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105011","DOI":"10.1016\/j.msard.2023.105011","article-title":"Age-related differences in the severity of sexual dysfunction symptoms and psychological distress in individuals with multiple sclerosis","volume":"79","author":"Romano","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s40279-022-01748-2","article-title":"Fatigue and Human Performance: An Updated Framework","volume":"53","author":"Behrens","year":"2023","journal-title":"Sports Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lane, A.M., Micklewright, D., and Meijen, C. (2025). Understanding fatigue: A psychological framework for health and performance. Sci, 7.","DOI":"10.3390\/sci7040162"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/sleep\/33.8.1061","article-title":"Fatigue in multiple sclerosis: Mechanisms, evaluation, and treatment","volume":"33","author":"Braley","year":"2010","journal-title":"Sleep"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.janxdis.2015.05.003","article-title":"Anxiety sensitivity and the anticipation of predictable and unpredictable threat: Evidence from the startle response and event-related potentials","volume":"33","author":"Nelson","year":"2015","journal-title":"J. Anxiety Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102261","DOI":"10.1016\/j.msard.2020.102261","article-title":"Anxiety and depression in Multiple Sclerosis (MS): Antecedents, consequences, and differential impact on well-being and quality of life","volume":"44","author":"Hanna","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e182","DOI":"10.1016\/j.esxm.2016.02.004","article-title":"The Relationship Between Body Image and Domains of Sexual Functioning Among Heterosexual, Emerging Adult Women","volume":"4","author":"Benson","year":"2016","journal-title":"Sex. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"106226","DOI":"10.1016\/j.msard.2024.106226","article-title":"The association between body image and psychological outcomes in multiple sclerosis. A systematic review","volume":"93","author":"McCormack","year":"2025","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pego P\u00e9rez, E.R., Bermello L\u00f3pez, M.L., G\u00f3mez Fern\u00e1ndez, E., and Mar\u00edn Arn\u00e9s, M.D.R. (2025). Predicting Quality of Life in Relapsing-Remitting Multiple Sclerosis: Clinical Burden Meets Emotional Balance in Early Disease. Neurol. Int., 17.","DOI":"10.3390\/neurolint17120195"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dourou, P., Gourounti, K., Lykeridou, A., Gaitanou, K., Petrogiannis, N., Athanasiadou, C.R., Sousamli, A., Xanthos, T., and Sarantaki, A. (2024). Evaluating sexual health in women with multiple sclerosis: A study on the interplay of disability and quality of life. Healthcare, 12.","DOI":"10.20944\/preprints202405.1450.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/jsxmed\/qdaf015","article-title":"Sexual dysfunction in female patients with multiple sclerosis: Relationship with functional status, fatigue, depression, sleep quality, and quality of life","volume":"22","author":"Yeni","year":"2025","journal-title":"J. Sex. Med."},{"key":"ref_38","first-page":"13","article-title":"Effects of sexual dysfunction, fatigue, and Depression on the quality of life of women with multiple sclerosis","volume":"2","author":"Mavioglu","year":"2022","journal-title":"J. Mult. Scler. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:57:30Z","timestamp":1773820650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["jcm15062304"],"URL":"https:\/\/doi.org\/10.3390\/jcm15062304","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]}}}