Background: Vitamin D deficiency is considered a risk factor for autoimmune
diseases. Vitamin D and its analogues have been proposed as therapeutic tools in autoimmunity
considering their exquisite immunoregulatory effect against over-reactivity towards tolerance.
Autoimmune diseases, nowadays recognized as emerging non communicable diseases,
are characterized by a significant female bias. This sexual dimorphism seems related to
sex hormones, which differently affect male and female immune systems. Males show higher
immunosuppression, maybe due to androgens; the greater female immunoreactivity and competence,
likely related to estrogens, lead to a greater resilience to infections but also to a
higher risk for autoimmunity. Higher interest could be given to vitamin D-based supplementation
or therapy for autoimmune diseases in relation to gender as well.
Objective: This review aims to discuss the role of vitamin D in autoimmune diseases with a
view inside gender-related differences, in light of the interplay between vitamin D and sex
hormones, especially estrogens.
Results: Some beneficial effects against autoimmune processes seem to be allowed by vitamin
D acting in synergy with estrogens. This observation suggests that possible differences of
vitamin D effects depend on the context in which this hormone is active.
Conclusion: Rather sex-related differences of “absolute” vitamin D levels, the role of gender-
dependent factors affecting vitamin D action seems to be critical. Gender and sexual
hormones could be included as variables when evaluating the potential power of vitamin D
receptor agonists as novel pharmacological tools to approach autoimmune diseases.