Multiple sclerosis (MS) is an autoimmune disease of central nervous system which is characterized with demyelination. Prolactin, synthesized in the anterior pituitary cells, has a role in maturation of immune cells, suggesting its possible implication in autoreactivity. The aim of the current study is to investigate the role of hyperprolactinemia in MS. Twenty-two MS patients with hyperprolactinemia diagnosed with pituitary adenoma and 66 MS patients without hyperprolactinemia were enrolled in our case-control study. They were matched with regard to age, gender, and MS subtypes. Patients with other concomitant autoimmune diseases and pregnancy were excluded. Statistical analyses were carried out using SPSS (SPSS statistic package, version 21.0.0) statistical software. The Pearson Chi-square test and the t test were used to determine whether there were any significant differences. The level of significance was set at p < 0.05. Greater value of relapse rate among hyperprolactinemic MS patients in comparison to non-hyperprolactinemic MS patients was statistically significant (p < 0.001). Statistically significant difference between the two groups in terms of EDSS was observed (case group vs.
Control: 1.3 vs. 1.9; p = 0.007). The correlation between MS duration and duration of hyperprolactinemia was significant in the case group (p < 0.05, R = 0.752). No statistically significant difference was found between two groups regarding duration of MS. This study suggested a protective role of prolactin in demyelinating procedure of MS.