Men with lower testosterone and higher estradiol-to-testosterone ratio hospitalized for COVID-19 may be at increased risk for more severe disease and mortality, according to the results of findings from a prospective cohort study published in JAMA Network Open.

Serum samples were collected from patients admitted with COVID-19 to the Barnes Jewish Hospital in St. Louis between March and May of 2020. Samples were assessed for hormones and cytokines and related with clinical outcomes.

The cohort (N=152) consisted of 59.2% men and mean age was 63 years (standard deviation [SD], 16). Common COVID-19 symptoms included shortness of breath (61.8%), fever (57.9%), and nonproductive cough (55.2%).


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Nearly one-quarter of the patients (24.3%) died.

Stratified by gender, men had lower average body mass index (27.7 vs 33.0 kg/m2; P <.001) and higher median testosterone concentrations (79 vs 12 ng/dL; P <.001).

At day 0, 89.5% of men had lower-than-normal (<250 ng/dL) testosterone levels. Baseline testosterone was negatively correlated with Charlson Comorbidity Index (CCI; r, -0.32; P =.005) and positively correlated with insulin-like growth factor 1 (r, 0.32; P =.01). Testosterone was observed to decrease during hospitalization.

Men with severe COVID-19 (n=66) were older (P <.001) and had higher CCI scores (P =.02). At admission, testosterone was 64.9% lower among mean with severe disease

(P =.008), at day 3 testosterone was 82.9% lower (P =006), and at day 7 testosterone was 84.1% lower (P =.02). Baseline testosterone level was associated with hepatocyte growth factor (β, -0.46; P <.001), interleukin (IL)-6 (β, -0.43; P <.001), C-reactive protein (β, -0.38; P =.004), interferon γ–inducible protein 10 (β, -0.32; P =.007), and IL-1ra (β, -0.29; P =.02).

Baseline estradiol-to-testosterone ratio was increased among men who were admitted to the intensive care unit (P <.001), required mechanical ventilation (P =.001), and who died (P =.009). Estradiol-to-testosterone ratio on day 3 was associated with hepatocyte growth factor (β, 0.61; P =.001), IL-6 (β, 0.58; P =.001), monokine induced by γ interferon (β, 0.51; P =.006), monocyte chemoattractant protein 1 (β, 0.50; P =.004), and interferon γ–inducible protein 10 (β, 0.46; P =.008).

Severe disease developed among women who were older (P <.001) and with higher CCI score (P <.001). In women, hormone concentrations did not differ on the basis of disease severity; however, women who required mechanical ventilation had higher estradiol at admission (median, 47 vs 10 pg/mL; P =.02).

This study may have been limited by not assessing free or bioavailable testosterone.

The study authors concluded that severe COVID-19, inflammation, and mortality was associated with lower testosterone concentrations and higher estradiol-to-testosterone ratio among men.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Dhindsa S, Zhang N, McPhaul MJ, et al. Association of circulating sex hormones with inflammation and disease severity in patients with COVID-19. JAMA Netw Open. 2021;4(5):e2111398. doi:10.1001/jamanetworkopen.2021.11398