Association of male hypogonadism with risk of hospitalization for COVID-19

Importance: Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh). Objective: To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh. Design, Setting, and Participants: This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021. Exposures: The primary exposure was gonadal status (hypogonadism, eugonadism, and TTh). Hypogonadism was defined as a total testosterone concentration below the limit of normal provided by the laboratory (which varied from 175 to 300 ng/dL [to convert to nanomoles per liter, multiply by 0.0347]). Main Outcomes and Measures: The primary outcome was rate of hospitalization for COVID-19. Statistical adjustments were made for group differences in age, body mass index, race and ethnicity, immunosuppression, and comorbid conditions. Results: Of the 723 study participants (mean [SD] age, 55 [14] years; mean [SD] body mass index, 33.5 [7.3]), 116 men had hypogonadism, 427 had eugonadism, and 180 were receiving TTh. Men with hypogonadism were more likely than men with eugonadism to be hospitalized with COVID-19 (52 of 116 [45%] vs 53 of 427 [12%]; P \u3c .001). After multivariable adjustment, men with hypogonadism had higher odds than men with eugonadism of being hospitalized (odds ratio, 2.4; 95% CI, 1.4-4.4; P \u3c .003). Men receiving TTh had a similar risk of hospitalization as men with eugonadism (odds ratio, 1.3; 95% CI, 0.7-2.3; P = .35). Men receiving inadequate TTh (defined as subnormal testosterone concentrations while receiving TTh) had higher odds of hospitalization compared with men who had normal testosterone concentrations while receiving TTh (multivariable adjusted odds ratio, 3.5; 95% CI, 1.5-8.6; P = .003). Conclusions and Relevance: This study suggests that men with hypogonadism were more likely to be hospitalized after COVID-19 infection compared with those with eugonadism, independent of other known risk factors. This increased risk was not observed among men receiving adequate TTh. Screening and appropriate therapy for hypogonadism need to be evaluated as a strategy to prevent severe COVID-19 outcomes among men

Association of circulating sex hormones with inflammation and disease severity in patients with COVID-19

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 among patients 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. Results: Among 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; P = .01) and day 3 (19 [6 to 68] ng/dL vs 111 [49 to 274] ng/dL; P = .006) compared with 24 men with milder disease. Testosterone concentrations were inversely associated with concentrations of interleukin 6 (β = -0.43; 95% CI, -0.52 to -0.17; P \u3c .001), C-reactive protein (β = -0.38; 95% CI, -0.78 to -0.16; P = .004), interleukin 1 receptor antagonist (β = -0.29; 95% CI, -0.64 to -0.06; P = .02), hepatocyte growth factor (β = -0.46; 95% CI, -0.69 to -0.25; P \u3c .001), and interferon γ-inducible protein 10 (β = -0.32; 95% CI, -0.62 to -0.10; P = .007). Estradiol and IGF-1 concentrations were not associated with COVID-19 severity in men. Testosterone, estradiol, and IGF-1 concentrations were similar in women with and without severe COVID-19. Gene set enrichment analysis revealed upregulated hormone signaling pathways in CD14+CD16- (ie, classical) monocytes and CD14-CD16+ (ie, nonclassical) monocytes in male patients with COVID-19 who needed intensive care unit treatment vs those who did not. Conclusions and Relevance: In this single-center cohort study of patients with COVID-19, lower testosterone concentrations during hospitalization were associated with increased disease severity and inflammation in men. Hormone signaling pathways in monocytes did not parallel serum hormone concentrations, and further investigation is required to understand their pathophysiologic association with COVID-19

Insulin as an anti-inflammatory and antiatherosclerotic hormone

Fasting hyperinsulinemia is associated with an increased risk of atherosclerotic complications, namely heart attack and stroke, which has led to the concept that insulin may promote atherosclerosis despite the absence of any evidence that insulin is atherogenic either in humans or in experimental models. Recent evidence shows that insulin exerts vasodilatory, antiplatelet, and anti-inflammatory effects at the cellular level in vitro and in humans in vivo. Because atherosclerosis is an inflammatory process, insulin is probably antiatherosclerotic in the long-term. Recent data on experimental atherosclerosis in mice show that (a) insulin administration reduces the number and the size of atherosclerotic lesions in apolipoprotein E null mice; and (b) in insulin receptor substrate-2 null mice, the interruption in insulin signal transduction results in enhanced atherogenicity. The use of a low dose of insulin infusion in patients with acute myocardial infarction (AMI) has been shown to markedly improve clinical outcomes both in diabetic and nondiabetic patients. The authors' most recent data show that a low-dose infusion of insulin in patients with AMI induces a reduction in inflammation (C-reactive protein and serum amyloid A) and oxidative stress and may have a role in myocardial protection. The authors conclude that insulin is both anti-inflammatory and antiatherogenic and may be of use in the treatment of cardiovascular inflammatory conditions, including AMI

Association of poor glycemic control with prolonged hospital stay in patients with diabetes admitted with exacerbation of congestive heart failure

To establish a relationship between the control of blood glucose levels and the severity of congestive heart failure (CHF) in a retrospective review of medical records of patients with diabetes admitted with acute exacerbation of CHF and to assess the potential correlation between the number of days of hospitalization and the baseline and in-hospital glycemic status. Medical records were reviewed to identify patients with diabetes admitted to a tertiary care center with exacerbation of CHF. Patients in whom any new complications developed that could have prolonged the hospitalization were excluded from the study. The number of days of hospitalization attributable to CHF were noted and statistically correlated with the glycemic control. Data on 100 patients included in the study are presented. The duration of hospitalization ranged from 1 day to 2 weeks (mean, 4.79 +/- 3.03 days). The in-hospital glycemic control strongly correlated positively with the number of days of hospitalization (r = 0.499; 95% confidence interval [CI], 0.325 to 0.643). The admission blood glucose level also showed a strong positive correlation with the days of hospitalization (r = 0.587; 95% CI, 0.426 to 0.720). The mean hemoglobin A1c (HbA1c) correlated positively with the number of days in the hospital (r = 0.653; 95% CI, 0.508 to 0.764). The 51 patients with uncontrolled diabetes (HbA1c >7%) were hospitalized for a mean period of 6.3 +/- 3.2 days, in comparison with a mean duration of 3.2 +/- 1.9 days for the 49 patients with good outpatient glycemic control (HbA1c < or =7%). Patients with diabetes admitted with exacerbation of CHF who have poor baseline or in-hospital glycemic control have a prolonged hospitalization