Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19

Abstract

IMPORTANCE Male sex is a risk factor for developing severe COVID-19 illness. It is not known whether sex hormones contribute to this predisposition. OBJECTIVE To investigate the association of concentrations of serum testosterone, estradiol, and insulinlike growth factor 1 (IGF-1, concentrations of which are regulated by sex hormone signaling) with COVID-19 severity. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study was conducted using serum samples collected from consecutive patients who presented from March through May 2020 to the Barnes Jewish Hospital in St Louis, Missouri, with COVID-19 (diagnosed using nasopharyngeal swabs).EXPOSURES Testosterone, estradiol, and IGF-1 concentrations were measured at the time of presentation (ie, day 0) and at days 3, 7, 14, and 28 after admission (if the patient remained hospitalized). MAIN OUTCOMES AND MEASURES Baseline hormone concentrations were compared amongpatients who had severe COVID-19 vs those with milder COVID-19 illness. RNA sequencing was performed on circulating mononuclear cells to understand the mechanistic association of altered circulating hormone concentrations with cellular signaling pathways. RESULTSAmong 152 patients (90 [59.2%] men; 62 [40.8%] women; mean [SD] age, 63 [16] years), 143 patients (94.1%) were hospitalized. Among 66 men with severe COVID-19, median [interquartile range] testosterone concentrations were lower at day 0 (53 [18 to 114] ng/dL vs 151 [95 to 217] ng/dL;

Proxalutamide Improves Inflammatory, Immunologic, and Thrombogenic Markers in Mild-to-Moderate COVID-19 Males and Females: an Exploratory Analysis of a Randomized, Double-Blinded, Placebo-Controlled Trial Early Antiandrogen Therapy (EAT) with Proxalutamide (The EAT-Proxa Biochemical AndroCoV-Trial)

“…In accordance with this hypothesis, recent work has correlated lower level of testosterone in males to worse prognosis when dosed during COVI-19. 32 This reinforces the better outcomes observed in this population with proxalutamide.…”

The chicken or the egg: low testosterone predisposes for COVID-19 or COVID-19 induces a decrease in testosterone?

“…Recently, an inverse association between testosterone concentrations and disease severity in male but not female COVID-19 patients was reported [ 1 ]. COVID-19 is characterized by systemic inflammation and men are more likely to be severely affected than women.…”

An Overview of Sex Hormones in Relation to SARS-CoV-2 Infection

“…Furthermore, there is evidence that in patients with respiratory tract infections without COVID-19, TT levels were higher than in patients with COVID-19 infection, but both groups had lower levels of TT compared with the control group [ 42 ]. A recent cohort study by Dhindsa et al on 90 males and 62 females with COVID-19 revealed that lower testosterone levels in males were associated with increased severity of COVID-19, inflammatory markers and disease-related mortality [ 43 ]. Another study also demonstrated that low TT and calculated free testosterone at admission were associated with poor outcomes [ 44 ].…”