Hidden Challenges: A Cross-Sectional Study on Prevalence and Determinants of Sexual Dysfunction in Men and Women with Multiple Sclerosis

<i>Background and Objectives:</i> Sexual dysfunction (SD) is common in multiple sclerosis (MS) but remains under-recognized in routine care. This study aimed to quantify the burden of SD in men and women with relapsing-remitting MS (RRMS), describe sex-stratified patterns across primary/secondary/tertiary domains, and examine associations with fatigue and MS-related health-related quality of life (HRQoL). <i>Materials and Methods:</i> In this cross-sectional observational study, RRMS participants were voluntarily recruited online via a QR code linking to a Google Forms survey. Men completed the International Index of Erectile Function-5 (IIEF-5), and women the Female Sexual Function Index (FSFI). MS-specific SD domains were assessed using the Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ), alongside the Fatigue Severity Scale (FSS) and the Multiple Sclerosis Quality of Life questionnaire (MSQOL-54). Sex differences were tested using parametric/non-parametric methods as appropriate, with false discovery rate (FDR) and Bonferroni adjustments for multiple comparisons. <i>Results:</i> Thirty-seven participants were included (16 men; 21 women). Mean age did not differ by sex (35.9 ± 4.0 vs. 38.9 ± 10.4 years; <i>p</i> = 0.23). All participants reported at least some degree of difficulty across MSISQ domains. Among men, 87.5% screened positive for erectile dysfunction within this sample (mild 37.5%, mild-to-moderate 12.5%, moderate 12.5%, severe 25.0%). When dysfunction type was defined as the highest MSISQ domain score, secondary SD was most frequent in both sexes (75.0% men; 76.2% women; <i>p</i> = 0.49). Women showed higher secondary domain scores at the uncorrected level (<i>p</i> = 0.04), but this did not survive FDR correction. In HRQoL and symptom measures, women reported markedly higher fatigue (FSS 46.1 ± 12.4 vs. 25.5 ± 12.7; <i>p</i>_FDR < 0.001) and poorer physical health indices, including pain-related outcomes. <i>Conclusions:</i> SD has represented a substantial burden within this RRMS sample, with secondary domain predominance in both sexes, highlighting the clinical relevance of symptom-related and functional interference. These findings support the value of multidimensional sexual health assessment in clinical research settings and may be relevant for clinical assessment and future research in MS.