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. 2021 Jan;9(1):88-98.
doi: 10.1111/andr.12821. Epub 2020 Jun 3.

Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients

Giulia Rastrelli  1 , Vincenza Di Stasi  1 , Francesco Inglese  2 , Massimiliano Beccaria  2 , Martina Garuti  2 , Domenica Di Costanzo  2 , Fabio Spreafico  2 , Graziana Francesca Greco  2 , Giulia Cervi  2 , Antonietta Pecoriello  2 , Angela Magini  1 , Tommaso Todisco  1 , Sarah Cipriani  1 , Elisa Maseroli  1 , Giovanni Corona  3 , Andrea Salonia  4 , Andrea Lenzi  5 , Mario Maggi  6   7 , Giuseppe De Donno  2 , Linda Vignozzi  1   7
Affiliations

Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients

Giulia Rastrelli et al. Andrology. 2021 Jan.

Abstract

Background: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS-CoV-2 infection on women and men have suggested a potential role for testosterone (T) in determining gender disparity in the SARS-CoV-2 clinical outcomes.

Objectives: To estimate the association between T level and SARS-CoV-2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the respiratory intensive care unit (RICU).

Materials and methods: A consecutive series of 31 male patients affected by SARS-CoV-2 pneumonia and recovered in the respiratory intensive care unit (RICU) of the "Carlo Poma" Hospital in Mantua were analyzed. Several biochemical risk factors (ie, blood count and leukocyte formula, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, D-dimer, fibrinogen, interleukin 6 (IL-6)) as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined.

Results: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (ie, the neutrophil count, LDH, and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase in both ICU transfer and mortality risk was observed in men with TT < 5 nmol/L or cFT < 100 pmol/L.

Discussion and conclusion: Our study demonstrates for the first time that lower baseline levels of TT and cFT levels predict poor prognosis and mortality in SARS-CoV-2-infected men admitted to RICU.

Keywords: COVID-19; inflammatory markers; mortality; prognosis; sex hormones.

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Conflict of interest statement

The authors declare that there are no conflicts of interest in connection with this article.

Figures

Figure 1
Figure 1
Hormone and sex hormone–binding globulin levels according to different clinical outcomes. Data are expressed as box plot, with median and interquartile range; whiskers represent minimum and maximum values; circles and asterisks represent the outliers and extreme outliers. p1 is the significance level for one‐way ANOVA on ranks (Kruskal‐Wallis test) for testing the differences among the four groups; p2 is the significance level for one‐way ANOVA on ranks (Kruskal‐Wallis test) after excluding the RICU group. Abbreviations: IM = internal medicine inpatient clinics; RICU = respiratory intensive care unit; ICU = intensive care unit
Figure 2
Figure 2
Relationship between total testosterone and blood inflammatory markers of severity of SARS‐CoV‐2 pneumonia. The smooth curves were carried out by locally weighted scatterplot smoothing (LOWESS) analysis. Abbreviations: LDH = lactate dehydrogenase
Figure 3
Figure 3
Relationship between calculated free testosterone and blood inflammatory markers of severity of SARS‐CoV‐2 pneumonia. The smooth curves were carried out by locally weighted scatterplot smoothing (LOWESS) analysis. Abbreviations: LDH = lactate dehydrogenase
Figure 4
Figure 4
Relationship between total or calculated free testosterone and estimated probability of different clinical outcomes in SARS‐CoV‐2 pneumonia patients based on T levels. The smooth curves were carried out by locally weighted scatterplot smoothing (LOWESS) analysis. Abbreviations: IM = internal medicine inpatient clinics; ICU = intensive care unit
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