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 5

Longitudinal changes in inflammatory cytokine concentrations by sex during treatment for TB.

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Longitudinal changes in inflammatory cytokine concentrations by sex duri...
The x axes show study visits (baseline, month 2, and month 6), and the y axes represent log-transformed cytokine concentrations in the serum. The first 2 columns represent longitudinal assessment of the changes in cytokine concentrations in males (blue box plots) and in females (red box plots) during the study (baseline, month 2, and month 6). The last column shows the comparison of cytokine concentrations between males and females. For each box-and-whisker plot, bounds of the boxes are quartile 1 (25th percentile) and quartile 3 (75th percentile), the line within the box represents the median value, whiskers show maximum and minimum values, and the dots outside the box are outlying values. Wilcoxon’s matched-pairs signed-rank test was used for between-time-point comparisons shown in A, B, D, E, G, H, J, K, M, N, P, and Q. Wilcoxon’s rank-sum test was used for sex comparisons within each time point for C, F, I, L, O, and R. *P < 0.05; **P < 0.001; ***P < 0.0001, ****P < 0.00001.