Gonadal steroids as predictors of sex differences in tuberculosis outcomes

Recent evidence suggests a role for biological factors to explain increased risk for active pulmonary tuberculosis (PTB) among men. We conducted a prospective cohort study in Mali of treatment naive males and females with laboratory-confirmed PTB and latent TB infection (LTBI) and healthy controls of similar ages to determine the relationship between alterations in gonadal steroids, tuberculosis (TB) disease status, and treatment outcomes. Prior to treatment, males with PTB had lower testosterone concentrations compared to males with LTBI or healthy males. Reduced testosterone concentrations in males with PTB were transient, returning healthy ranges by month 2 of treatment, which corresponded to the end of intensive TB treatment. Estradiol concentrations in females were not altered by PTB or infection status yet increased at month 6 of treatment. Testosterone, but not estradiol, was a strong predictor of cure during treatment. Testosterone, but not estradiol, concentrations in PTB cases were inversely correlated with IFN-γ, IL-6, and IL-2. Concentrations of IL-17 and IL-10 were lower in males than females at the end of TB treatment. Our results suggest that TB-induced changes in testosterone concentrations during PTB and in response to treatment occur in males and could contribute to sex differences in TB pathogenesis.