Testosterone in Relapsing-Remitting Multiple Sclerosis: A Case-Control Study

Background/Objectives: This study aimed to evaluate the prevalence of hypogonadism in men with RRMS (relapsing-remitting multiple sclerosis) who are undergoing treatment with disease-modifying therapies (DMTs) and its association with clinical and magnetic resonance imaging (MRI) parameters. Methods: A total of 126 male patients with RRMS, aged 18-67 years, receiving DMTs and a group of 35 age- and BMI-matched healthy individuals were enrolled. Clinical and demographic data were collected, including neurological disability (EDSS, T25FW, 9-HTP, SDMT), and MRI findings. Symptoms of androgen deficiency and depression were assessed using ADAM questionnaire and Beck Depression Inventory, while quality of life was evaluated using MSIS-29. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and free testosterone (fT) were measured in two stored morning blood samples. Results: A total of 118 (93.6%) MS patients (median age of 38.8 y) had normal TT levels; only 2 (1.6%) MS patients and 2 (5.7%) healthy controls had below-normal levels. Meanwhile, low fT levels were observed in 53 (43.7%) MS patients and 12 (34.3%) controls. However, the fT level was significantly lower in the MS patients under 38 years of age than in control individuals (p = 0.015). Only depression from all concomitant diseases was more prevalent in MS patients with low fT (p = 0.016). There was no correlation between low fT and clinical (EDSS, T25FT, SDMT) and MRI (new T2 and new Gd+ lesions) parameters but a longer disease duration and a higher total number of steroid treatments were associated with below-normal fT levels (p = 0.048 and p = 0.003, respectively). Change of DMT and current and previous DMT type did not correlate with low fT. Patients with low fT levels had a higher median score on the BDI (8.00; IQR: 3.00-12.50 vs. 5.00; IQR: 1.00-10.50) (p = 0.034) and the higher median ADAM questionnaire score (4.00 [IQR: 2.00-7.50] vs. 2.00 [IQR: 0.00-6.00]) (p = 0.034). Only a longer duration of MS (11.83 years) exhibited a significant positive correlation with the risk of a low fT level (OR = 1.19, CI 95%: 1.06-1.35, p = 0.004) in multivariate logistic analysis. Conclusions: Total testosterone level was normal in most male RRMS patients; however, low free testosterone level was observed, in particular in younger MS patients. Depression was more prevalent in patients with low fT but longer duration was a significant risk factor for a low fT level.