Associations between COVID-19 infection and sex steroid hormones

Abstract

AimsCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and within a few months of the first outbreak, it was declared a global pandemic by the WHO. The lethal virus SARS-CoV-2 is transmitted through respiratory droplets and enters host cells through angiotensin-converting enzyme 2 (ACE-2) receptors. ACE-2 receptors are highly expressed in many tissues, including testes. Therefore, the objective of this study was to summarize the available literature regarding the correlation between sex hormone levels and COVID-19.MethodsThe PubMed, Web of Science, Embase, and Cochrane Library databases were reviewed systematically through August 2022 for studies comparing sex hormone levels between different patient groups: COVID-19 versus no COVID-19, more severe versus less severe COVID-19, and non-survivors versus survivors. Various types of clinical research reporting sex hormone levels, including free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17β-oestradiol (E2), the oestradiol-to-testosterone ratio (E2/T), prolactin (PRL), and sex hormone-binding globulin (SHBG), were included. Random- or fixed-effects models were used to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity among the studies was assessed by the I2 index, and data analyses were performed using meta-analysis with Stata version 12.0.ResultsTwenty-two articles that included 3369 patients were ultimately included in the meta-analysis. According to analysis of the included studies, patients with COVID-19 had significantly low T/LH, FSH/LH, and SHBG levels and high levels of LH, and E2/T, but their levels of FT, FSH, PRL, E2, and progesterone were not affected. Publication bias was not found according to funnel plots and Egger’s regression and Begg’s rank correlation tests.ConclusionLow T/LH, FSH/LH, and SHBG serum levels and high LH, and E2/T levels may increase the risk of COVID-19. Additionally, the greater is the clinical severity of COVID-19, the higher is the probability of increases in LH, and E2/T serum levels and decreases in T/LH, FSH/LH, and SHBG levels. COVID-19 may have unfavourable effects on gonadal functions, which should be taken seriously by clinicians. Routine monitoring of sex hormone levels might help clinicians to evaluate disease severity in patients with COVID-19.

Effect of COVID‐19 infection on sex hormone levels in hospitalized patients: A prospective longitudinal study in Iran

“… 19 In line with our results, a systematic review on the level of male sex hormones showed that in patients with severe COVID‐19 infection, the level of total testosterone decreased significantly, and even men with lower levels of testosterone experienced more severe disease and mortality. 20 Similar to our results, Dhindsa et al 11 in a study on 152 hospitalized patients found that men with severe disease had lower levels of testosterone in comparison to men with mild or moderate disease. Consistent with our results, Zeggeren et al 21 in a small study on 40 patients found that the level of total and free testosterone was significantly lower in patients with severe disease and in those who died from severe disease compared to survivors.…”

Pituitary–gonadal hormones associated with respiratory failure in men and women hospitalized with COVID-19: an observational cohort study

“…On the other hand, the high prevalence of secondary hypogonadism in all three patient groups could be due to reduced gonadotropin-releasing hormone pulsatility, which is a known phenomenon during acute disease and physiological stress, and may suggest that testosterone concentrations reflect disease severity (27,28,29). Spratt et al studied pituitary-gonadal changes in men undergoing coronary artery bypass graft at pre-admission, during surgery, and the following days post-surgery as a model for acute severe disease (8). As in our study, they found that the study population had decreased concentrations of testosterone, LH, and FSH and increased concentrations of estrone and estradiol as early as the day after surgery.…”

“…Concentrations of gonadal hormones differ between sexes, and gonadal and pituitary hormones have been suggested to play a role in disease progression. Studies have reported association of the hypothalamic-pituitary-gonadal (HPG) axis in men hospitalized with COVID-19 with severely suppressed concentrations of testosterone and increased concentrations of estradiol with a reported association to mortality and respiratory failure (2,3,4,5,6,7,8). Additionally, severe COVID-19 is driven by hyperinflammation as reflected by high circulating levels of inflammatory biomarkers such as C-reactive protein (CRP) and interleukin (IL)-6.…”

Sex difference in the cytokine profile among patients hospitalized for COVID-19 and during their recovery: predominance of females in adhesion molecules and males in oxidative stress

“…FSH, total, free, and bioavailable testosterone levels were lower in patients who required admission to the ICU [34]. Additionally, the greater clinical severity of COVID-19, the higher is the probability of increases in LH, and E2/T serum levels and decreases in SHBG levels [37]. Low SHBG levels were associated with mortality in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men [38].…”