Gonadal steroids as predictors of sex differences in tuberculosis outcomes

BACKGROUNDRecent evidence suggests a role for biological factors in increased risk for active pulmonary tuberculosis (PTB) among males. We determined the relationship between alterations in gonadal steroids, tuberculosis (TB) disease status, and treatment outcomes. METHODSWe conducted a prospective cohort study in Mali of treatment naïve males and females with laboratory-confirmed PTB, latent TB infection (LTBI), and healthy controls of similar ages. RESULTSPrior 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 to 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 serum 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. CONCLUSIONOur 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. FUNDINGThe Fogarty International Center and the Office of Research on Women's Health (K43TW011426); the Institute for Global Health at the Feinberg School of Medicine of the Northwestern University (Catalyzer Award); 2021 TWAS Abdool Karim Award; NIH grants R37AI167750 and 5D43TW010350.