No association between circulating levels of testosterone and sex hormone-binding globulin and risk of COVID-19 mortality in UK biobank

  1. Xikang Fan
  2. Jing Yang
  3. Jiayu Wang
  4. Cheng Yin
  5. Meng Zhu
  6. Hongxia Ma
  7. Guangfu Jin
  8. Zhibin Hu
  9. Hongbing Shen
  10. Dong Hang

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Abstract

Background

Sex-disaggregated data suggest that men with coronavirus disease 2019 (COVID-19) are more likely to die than women. Whether circulating testosterone or sex hormone-binding globulin (SHBG) contributes to such sex differences remains unknown.

Objective

To evaluate the associations of circulating total testosterone (TT), free testosterone (FT), and SHBG with COVID-19 mortality.

Design

Prospective analysis.

Setting

UK Biobank.

Participants

We included 1306 COVID-19 patients (678 men and 628 women) who had serum TT and SHBG measurements and were free of cardiovascular disease or cancer at baseline (2006-2010).

Main outcome measures

The death cases of COVID-19 were identified from National Health Service death records updated at 31 July 2020. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CI) for mortality.

Results

We documented 315 deaths of COVID-19 (194 men and 121 women). After adjusting for potential confounders, we did not find any statistically significant associations for TT (OR per 1-SD increase = 1.03, 95% CI: 0.85-1.25), FT (OR per 1-SD increase = 0.95, 95% CI: 0.77-1.17), or SHBG (OR per 1-SD increase = 1.09, 95% CI: 0.87-1.37) with COVID-19 mortality in men. Similar null results were observed in women (TT: OR per 1-SD increase = 1.10, 95% CI: 0.85-1.42; FT: OR per 1-SD increase = 1.10, 95% CI: 0.82-1.46; SHBG: OR per 1-SD increase = 1.16, 95% CI: 0.89-1.53).

Conclusions

Our findings do not support a significant role of circulating testosterone or SHBG in COVID-19 prognosis.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.11.20191783: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableFinally, 1306 patients with COVID-19 were included in the analysis, consisting of 678 men and 628 women.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, two major limitations should be acknowledged. First, baseline hormones were assessed only one time, which may not reflect a long-time exposure. However, the intraclass correlation coefficients of TT and SHBG between two measurements (4 years apart in UK biobank) were 0.59 (95% CI: 0.58-0.61) and 0.86 (95% CI: 0.86-0.87), respectively, in men; 0.63 (95% CI: 0.62-0.64) and 0.81 (95% CI: 0.80-0.82), respectively, in women, indicating that a single measurement can reliably categorize average levels over at least a 4-year period (20). Second, limited by the coverage of COVID-19 testing, ascertainment bias may have occurred in the current study.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.09.11.20191783 on medRxiv