ABSTRACT Objectives Systemic sclerosis (SSc) demonstrates marked female predominance, suggesting hormonal influences in disease pathogenesis. The second‐to‐fourth digit ratio (2D:4D), a biomarker of prenatal androgen exposure, has been associated with various autoimmune conditions. This study investigated whether 2D:4D ratios differ between female SSc patients and healthy controls. Methods This case–control study enrolled 33 women with SSc (2013 ACR/EULAR criteria) and 30 age‐matched healthy female controls. Second and fourth digit lengths were measured bilaterally using digital calipers, and 2D:4D ratios were calculated. Between‐group differences were analyzed using Welch's t‐test and Mann–Whitney U test. Results SSc patients demonstrated significantly lower 2D:4D ratios than controls bilaterally (right hand: 0.950 ± 0.029 vs. 1.022 ± 0.012, p 2.8). The lower ratios resulted from longer fourth digits rather than shorter second digits, consistent with elevated prenatal androgen exposure. Conclusions Female SSc patients exhibit significantly lower 2D:4D ratios than healthy controls, suggesting higher prenatal testosterone exposure. These findings support the hypothesis that the prenatal hormonal environment may contribute to autoimmune disease susceptibility.
Yakar et al. (2026) studied this question.