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Randomized Controlled Trial
. 2018 Dec 4;19(1):240.
doi: 10.1186/s12931-018-0947-0.

Dihydrotestosterone is a predictor for mortality in males with community-acquired pneumonia: results of a 6-year follow-up study

Seline Zurfluh  1 , Manuela Nickler  2 , Manuel Ottiger  2 , Christian Steuer  3 , Alexander Kutz  2 , Mirjam Christ-Crain  4 , Werner Zimmerli  5 , Robert Thomann  6 , Claus Hoess  7 , Christoph Henzen  8 , Luca Bernasconi  9 , Andreas Huber  9 , Beat Mueller  2 , Philipp Schuetz  2 ; proHOSP study group
Collaborators, Affiliations
Randomized Controlled Trial

Dihydrotestosterone is a predictor for mortality in males with community-acquired pneumonia: results of a 6-year follow-up study

Seline Zurfluh et al. Respir Res. .

Abstract

Background: Adrenal hormone metabolite levels are altered in acute illnesses such as community-acquired pneumonia (CAP). Our aim was to investigate associations of sex and mineralocorticoid hormone metabolites with short- and long-term mortality and severity of CAP in male and female patients.

Methods: We prospectively followed 285 patients (60.4% male, mean age 71 years) with CAP from a previous multicenter trial. At baseline, levels of different metabolites of sex hormones and mineralocorticoids were measured by liquid chromatography coupled to tandem mass spectrometry. We calculated Cox regression models adjusted for age and comorbidities.

Results: All-cause mortality was 5.3% after 30 days and increased to 47.4% after 6 years. In males, high levels of dihydrotestosterone were associated with higher 6-year mortality (adjusted HR 2.84, 95%CI 1.15-6.99, p = 0.023), whereas high levels of 17-OH-progesterone were associated with lower 6-year mortality (adjusted HR 0.72, 95%CI 0.54-0.97, p = 0.029). Testosterone levels in males correlated inversely with inflammatory markers (CRP rho = - 0.39, p < 0.001; PCT rho = - 0.34, p < 0.001) and disease severity as assessed by the Pneumonia severity index (PSI) (rho = - 0.23, p = 0.003). No similar association was found for female patients.

Conclusion: Whereas in males with CAP, sex and mineralocorticoid hormone metabolite levels correlated with inflammation, disease severity and long-term survival, no similar association was found for females. Further study of sex and mineralocorticoid hormones in acute illness could generate predictive signatures with implementation in clinical practice.

Keywords: Adrenal hormones; Community-acquired pneumonia; Dihydrotestosterone; Mortality prediction.

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Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the ethics committee of the University of Basel as well as by the local ethics committees of Aarau, Muensterlingen, Solothurn and Luzern, all with the same ethical study number 87/06. Written informed consent was provided by all participants for the initial trial, including agreement to use their data anonymized in secondary analyses.

Consent for publication

Not applicable.

Competing interests

All authors declare that they have no competing interests associated with this manuscript.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Admission DHEA-S and testosterone levels with according disease severity (PSI and qSOFA) in males with CAP. Data are represented as median and IQR, with scatter plots representing each value. P values are determined by Kruskal-Wallis test and considered statistically significant at p < 0.05. Bold values indicate statistical significane. CAP, community-aquired pneumonia; DHEA-S, dihydroepiandrosterone-sulfate; PSI, pneumonia severity index; qSOFA, quick sequential organ failure assessment
Fig. 2
Fig. 2
Correlation of admission testosterone levels with acute inflammatory markers (CRP and PCT) in males with CAP. Data are presented with scatterplots showing all values (blue), overlaid by linear fit lines (red). We used admission hormone metabolite levels and peak values of CRP and PCT. Correlation analyses were performed by Spearman’s rank correlation (rho; p-value). p < 0.05 is considered statistically significant; bold values indicate statistical significance. We used multivariate linear regression models to calculate regression coefficients (coef). CAP, community-acquired pneumonia; CRP, c-reactive protein; PCT, procalcitonin. *Multivariate model is adjusted for age and comorbidities (coronary artery disease, cerebrovascular disease, chronic kidney disease, neoplastic disease)
See this image and copyright information in PMC

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