Gonadal steroids as predictors of sex differences in tuberculosis outcomes
Djeneba Dabitao, Bocar Baya, Ibrahim Sanogo, Amadou Somboro, Mamadou Wague, Mamadou D. Coulibaly, Isaac Koloma, Mahamadou Kone, Mohamed Nantoume, Nadie Coulibaly, Stephane Behinan, Mariam Coulibaly, Mamadou Perou, Moumine Sanogo, Ayouba Diarra, Seydou Samake, Bassirou Diarra, Mahamadou Diakite, Souleymane Diallo, Yacouba Toloba, Chad Achenbach, Jane L. Holl, Seydou Doumbia, Robert Murphy, William Bishai, Sabra Klein
Djeneba Dabitao, Bocar Baya, Ibrahim Sanogo, Amadou Somboro, Mamadou Wague, Mamadou D. Coulibaly, Isaac Koloma, Mahamadou Kone, Mohamed Nantoume, Nadie Coulibaly, Stephane Behinan, Mariam Coulibaly, Mamadou Perou, Moumine Sanogo, Ayouba Diarra, Seydou Samake, Bassirou Diarra, Mahamadou Diakite, Souleymane Diallo, Yacouba Toloba, Chad Achenbach, Jane L. Holl, Seydou Doumbia, Robert Murphy, William Bishai, Sabra Klein
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Clinical Research and Public Health Immunology Infectious disease

Gonadal steroids as predictors of sex differences in tuberculosis outcomes

Abstract

BACKGROUND Recent 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. METHODS We 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. RESULTS 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 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. CONCLUSION 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. FUNDING The 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.

Authors

Djeneba Dabitao, Bocar Baya, Ibrahim Sanogo, Amadou Somboro, Mamadou Wague, Mamadou D. Coulibaly, Isaac Koloma, Mahamadou Kone, Mohamed Nantoume, Nadie Coulibaly, Stephane Behinan, Mariam Coulibaly, Mamadou Perou, Moumine Sanogo, Ayouba Diarra, Seydou Samake, Bassirou Diarra, Mahamadou Diakite, Souleymane Diallo, Yacouba Toloba, Chad Achenbach, Jane L. Holl, Seydou Doumbia, Robert Murphy, William Bishai, Sabra Klein

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Figure 2

Changes in gonadal steroid concentrations in males and females by TB status and during treatment.

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Changes in gonadal steroid concentrations in males and females by TB sta...
(A) Testosterone concentrations in males at baseline in individuals with active pulmonary TB (PTB) and latent TB infection (LTBI) and healthy controls (Healthy). (B) Log-transformed estradiol concentrations in females with PTB and LTBI and healthy controls before commencing treatment. (C and D) Longitudinal assessment of testosterone concentrations in males with PTB (C) or LTBI (D) at different times points over a 6-month period. (E and F) Concentrations of estradiol on a log scale over time during the study period in females with PTB (E) or LTBI (F). Individual values for each participant and median ± interquartile range (IQR) are shown. Wilcoxon’s rank-sum test was used for group comparisons for A and B. Wilcoxon’s matched-pairs signed-rank test was used for comparison between time points for C–F. Dashed lines and gray zones represent median concentrations and IQR, respectively, of gonadal steroids in healthy donors of similar age and sex. *P < 0.05; **P < 0.001; ****P < 0.00001.