Association Between Sex Hormones Levels and Clinical Outcomes in Patients With COVID-19 Admitted to Hospital: An Observational, Retrospective, Cohort Study

Background: Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. Methods: This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. Findings: The median age was 73·5 years [IQR 61, 82]; 55·8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3·6 vs. 5·3 nmol/L, p =0·0378 and 3·7 vs. 8·5 nmol/L, p =0·0011, respectively). Deceased males had lower testosterone (2·4 vs. 4·8 nmol/L, p =0·0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0·0006). Testosterone was negatively associated with ARDS (OR 0·849 [95% CI 0·734, 0·982]), severe COVID-19 (OR 0·691 [95% CI 0·546, 0·874]), and in-hospital mortality (OR 0·742 [95% CI 0·566, 0·972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1·051 [95% CI 1·018, 1.084]), confirmed in both sex models.  Interpretation: In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes. Funding Information: The research was funded by Italian Ministry of Health “Fondi Ricerca Corrente, Project L1P5” for IRCCS Sacro Cuore Don Calabria Hospital. Declaration of Interests: We declare there is no conflict of interest. Ethics Approval Statement: Ethical approval for data collection was obtained in accordance with local regulations at each participating site. The study protocol received ethical approval and consent from the competent Ethics Committee (Comitato Etico per la sperimentazione Clinica delle Province di Verona e Rovigo) on September 1st, 2020 (protocol #46555).