Cryptococcosis, a fungal disease arising from the etiologic agent Cryptococcus neoformans, sickens a quarter of a million people annually, resulting in over 180,000 deaths. Interestingly, males are affected by cryptococcosis more frequently than females, a phenomenon observed for more than a half century. This disparity is seen in both HIV− (~3M:1F) and HIV⁺ (~8M:2F) populations of cryptococcal patients. In humans, male sex is considered a pre-disposing risk factor for cryptococcosis and males suffering from the disease have more severe symptoms and poorer outcomes. There are numerous observational, clinical and epidemiological studies documenting the male disadvantage in C. neoformans but with no further explanation of cause or mechanism. Despite being commonly acknowledged, little primary research has been conducted elucidating the reasons for these differences. The research that has been conducted, however, suggests sex hormones are a likely cause. Given that the sex difference is both prevalent and accepted by many researchers in the field, it is surprising that more is not known. This review highlights the data regarding differences in sexual dimorphism in C. neoformans infections and suggests future directions to close the research gap in this area.
Keywords: Cryptococcus; estrogen; immune privilege; neoformans; sex hormones; sex susceptibility; sexual dimorphism; testosterone.