The 2D:4D ratio, a proxy for prenatal androgen levels, differs in men with and without MS ABSTRACT Objective: To determine whether the 2D:4D ratio (ratio of the second and fourth digit lengths), a proxy for lower prenatal androgen to estrogen ratio, differs in men with and without multiple sclerosis (MS) using a case-control study design. Methods:We obtained 2 digital scans of the right hand for men with MS presenting to a scheduled clinic visit at a large MS referral center, and for men without autoimmune or endocrine diseases. All individuals were aged 18 to 65 years, right-handed, and reported no prior digit trauma. We calculated a mean 2D:4D ratio using digital calipers. In participants with MS, we assessed age at first MS symptoms, MS type, and the MS Severity Score; 51 had provided a testosterone level within 10 years of symptom onset. Our primary analysis was a cross-sectional comparison of the 2D:4D ratio between men with and without MS, using a 2-sample t test for independent samples assuming unequal variance.Results: In total, we scanned 137 men with MS and 145 men without MS. A statistically significant association between 2D:4D ratio and MS status was observed in the univariate logistic regression model (p , 0.05). These differences were not associated with age or race, which differed between the 2 groups. In participants with MS, the 2D:4D ratio was not correlated with MS type, age at first symptoms, or MS Severity Score (p . 0.15 for each), and it was not correlated with adult testosterone levels (r 5 0.06, p 5 0.68, n 5 51).Conclusions: During the prenatal period, low androgens could represent a risk factor for MS.