Does COVID-19 cause testicular damage? A cross-sectional study comparing hormonal parameters.

OBJECTIVE: We aimed to predict the potential testicular damage of COVID-19 by comparing the hormones FSH, LH, and TT before COVID-19 with values measured after COVID-19. PATIENTS AND METHODS: A total of 348 patients - who were followed up in our urology clinic for varicocele, premature ejaculation, erectile dysfunction and infertility, had FSH, LH and TT levels measured one year before COVID-19 and were positive for COVID-19 after a Polymerase Chain Reaction (RT-PCR) tests - were included in the study. Presence of pneumonia compatible with COVID-19, hospitalization in the intensive care unit and FSH, LH and TT values before and after COVID-19 were recorded, along with lung computed tomography (CT). RESULTS: The post-COVID-19 LH value (9.72±3.27 mIU/mL) of the patients was significantly higher than the pre-COVID-19 LH value (5.72±2.50 mIU/mL) (p<0.001). The post-COVID-19 TT (253.85±88.03 ng/dl) value was significantly lower than the pre-COVID-19 TT value (351.08±106.19 ng/dl) (p<.001). In addition, while there was a mean decrease of 127.8 ng/dl in TT level in patients with pneumonia, a decrease of 39.03 ng/dl was observed in patients without pneumonia (p<.001). CONCLUSIONS: COVID-19 may cause an increase in serum LH levels while decreasing TT levels. Additionally, those with COVID-19 pneumonia may experience a greater decrease in serum TT levels than those with COVID-19 without pneumonia.

Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19.

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers.

BACKGROUND: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. METHODS: Plasma levels of sex hormones (testosterone and 17ß-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. RESULTS: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. CONCLUSIONS: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.

Low testosterone predicts hypoxemic respiratory insufficiency and mortality in patients with COVID-19 disease: another piece in the COVID puzzle.

PURPOSE: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19). METHODS: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality. RESULTS: Subjects low T values (< 8 nmol/L; 176 cases) were significantly older (P = 0.001) and had higher serum interleukin-6 (P = 0.001), C-reactive protein (P < 0.001), lactate dehydrogenase (P < 0.001), ferritin (P = 0.012), lower P/F ratio (P = 0.001), increased prevalence of low T3 syndrome (P = 0.041), acute respiratory insufficiency (P < 0.001), more frequently need of ventilation (P < 0.001) and higher mortality rate (P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79-0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69-0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation. CONCLUSION: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.

Higher testosterone is associated with increased inflammatory markers in women with SARS-CoV-2 pneumonia: preliminary results from an observational study.

PURPOSE: Objective of this study was to assess the association between testosterone (T) levels and biochemical markers in a cohort of female patients admitted for SARS-CoV-2 infection in a respiratory intensive care unit (RICU). METHODS: A consecutive series of 17 women affected by SARSCoV-2 pneumonia and recovered in the RICU of the Hospital of Mantua were analyzed. Biochemical inflammatory markers as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. RESULTS: TT and cFT were significantly and positively associated with PCT, CRP, and fibrinogen as well as with a worse hospital course. We did not observe any significant association between TT and cFT with LH; conversely, both TT and cFT showed a positive correlation with cortisol. By LOWESS analysis, a linear relationship could be assumed for CRP and fibrinogen, while a threshold effect was apparent in the relationship between TT and procalcitonin, LDH and ferritin. When the TT threshold value of 1 nmol/L was used, significant associations between TT and PCT, LDH or ferritin were observed for values above this value. For LDH and ferritin, this was confirmed also in an age-adjusted model. Similar results were found for the association of cFT with the inflammatory markers with a threshold effect towards LDH and ferritin with increased LDH and ferritin levels for values above cFT 5 pmol/L. Cortisol is associated with serum inflammatory markers with similar trends observed for TT; conversely, the relationship between LH and inflammatory markers had different trends. CONCLUSION: Opposite to men, in women with SARS-CoV-2 pneumonia, higher TT and cFT are associated with a stronger inflammatory status, probably related to adrenal cortex hyperactivity.

Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19.

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.

Sex steroid hormones are associated with mortality in COVID-19 patients: Level of sex hormones in severe COVID-19.

ABSTRACT: In patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.We selected patients from the Amsterdam University Medical Centers COVID-19 Biobank, in which patients admitted to hospital in March and April 2020, with reverse transcription-polymerase chain reaction proven severe acute respiratory syndrome-coronavirus-2 infection, were prospectively included. Specifically, we included postmenopausal women (>55 years) and age-matched men, with a mortality of 50% in each group. Residual plasma samples were used to measure testosterone, estradiol, sex hormone binding globulin (SHBG), and albumin. We investigated the association of the levels of these hormones with mortality in men and women.We included 16 women and 24 men in March and April 2020 of whom 7 (44%) and 13 (54%), respectively, died. Median age was 69 years (interquartile range [IQR] 64-75). In men, both total and free testosterone was significantly lower in deceased patients (median testosterone 0.8 nmol/L [IQR 0.4-1.9] in deceased patients vs 3.2 nmol/L [IQR 2.1-7.5] in survivors; P < .001, and median free testosterone 33.2 pmol/L [IQR 15.3-52.2] in deceased patients vs 90.3 pmol/L [IQR 49.1-209.7] in survivors; P = .002). SHBG levels were significantly lower in both men and women who died (18.5 nmol/L [IQR 11.3-24.3] in deceased patients vs 34.0 nmol/L [IQR 25.0-48.0] in survivors; P < .001). No difference in estradiol levels was found between deceased and surviving patients.Low SHBG levels were associated with mortality rate in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men. The role of testosterone and SHBG and potential of hormone replacement therapy needs further exploration in COVID-19.

Testosterone in males with COVID-19: A 7-month cohort study.

BACKGROUND: Circulating testosterone levels have been found to be reduced in men with severe acute respiratory syndrome coronavirus 2 infection, COVID-19, with lower levels being associated with more severe clinical outcomes. OBJECTIVES: We aimed to assess total testosterone levels and the prevalence of total testosterone still suggesting for hypogonadism at 7-month follow-up in a cohort of 121 men who recovered from laboratory-confirmed COVID-19. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as total testosterone ≤9.2 nmol/L. The Charlson Comorbidity Index was used to score health-significant comorbidities. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and total testosterone levels at follow-up assessment. RESULTS: Circulating total testosterone levels increased at 7-month follow-up compared to hospital admittance (p < 0.0001), while luteinizing hormone and 17ß-estradiol levels significantly decreased (all p ≤ 0.02). Overall, total testosterone levels increased in 106 (87.6%) patients, but further decreased in 12 (9.9%) patients at follow-up, where a total testosterone level suggestive for hypogonadism was still observed in 66 (55%) patients. Baseline Charlson Comorbidity Index score (OR 0.36; p = 0.03 [0.14, 0.89]) was independently associated with total testosterone levels at 7-month follow-up, after adjusting for age, BMI, and IL-6 at hospital admittance. CONCLUSIONS: Although total testosterone levels increased over time after COVID-19, more than 50% of men who recovered from the disease still had circulating testosterone levels suggestive for a condition of hypogonadism at 7-month follow-up. In as many as 10% of cases, testosterone levels even further decreased. Of clinical relevance, the higher the burden of comorbid conditions at presentation, the lower the probability of testosterone levels recovery over time.

High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study.

Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. In this study, we analysed sex hormone levels (estradiol and testosterone) of male and female COVID-19 patients (n = 50) admitted to an intensive care unit (ICU) in comparison to control non-COVID-19 patients at the ICU (n = 42), non-COVID-19 patients with the most prevalent comorbidity (coronary heart diseases) present within the COVID-19 cohort (n = 39) and healthy individuals (n = 50). We detected significantly elevated estradiol levels in critically ill male COVID-19 patients compared to all control cohorts. Testosterone levels were significantly reduced in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Linear regression analysis revealed that among a broad range of cytokines and chemokines analysed, IFN-γ levels are positively associated with estradiol levels in male and female COVID-19 patients. Furthermore, male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment. Thus, we herein identified that disturbance of sex hormone metabolism might present a hallmark in critically ill male COVID-19 patients.

Impact of the SARS-CoV-2 virus on male reproductive health.

The coronavirus 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 160 million infections and 3.5 million deaths globally. Men are disproportionately affected by COVID-19, having more severe disease with higher mortality rates than women. Androgens have been implicated as the underlying cause for more severe disease, as the androgen receptor has been noted to upregulate the cell surface receptors that mediate viral cell entry and infection. Unfortunately, despite testosterone's potential role in COVID-19 prognosis, androgen deprivation therapy is neither protective nor a treatment for COVID-19. Interestingly, the male reproductive organs have been found to be vulnerable in moderate to severe illness, leading to reports of erectile dysfunction and orchitis. COVID-19 viral particles have been identified in penile and testis tissue, both in live patients who recovered from COVID-19 and post mortem in men who succumbed to the disease. Although sexual transmission remains unlikely in recovered men, moderate to severe COVID-19 infection can lead to germ cell and Leydig cell depletion, leading to decreased spermatogenesis and male hypogonadism. The objective of this review is to describe the impact of SARS-CoV-2 on male reproductive health. There are still many unanswered questions as to the specific underlying mechanisms by which COVID-19 impacts male reproductive organs and the long-term sequelae of SARS-CoV-2 on male reproductive health.

The relationship of serum testosterone levels with the clinical course and prognosis of COVID-19 disease in male patients: A prospective study.

BACKGROUND: A potential role of testosterone among sex hormones has been hypothesized in identifying sex-related differences in the clinical consequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Due to the high global prevalence of hypogonadism, the relationship between hypogonadism and SARS-CoV-2 infection outcomes deserves an in-depth study. OBJECTIVE: The present study aimed to investigate the relationship of serum testosterone with other laboratory parameters on the prognosis of coronavirus disease-19 (COVID-19) in male patients with COVID-19 diagnosis. MATERIALS AND METHODS: This prospective cohort study included 358 male patients diagnosed with COVID-19 and 92 COVID-19 negative patients admitted to the urology outpatient clinics as a control group. The COVID-19 patients were divided into groups according to prognosis (mild-moderate and severe group), lung involvement in chest computed tomography (<50% and >50%), intensive care unit needs, and survival. RESULTS: The measured serum total testosterone level of the COVID-19 patients group was found to be significantly lower than that of the control group (median, 140 ng/dl; range, 0.21-328, 322 ng/dl; range, median, 125-674, p < 0.001, respectively). The serum TT levels were statistically significantly lower in severe COVID-19 patients compared to mild-moderate COVID-19 patients (median, 85.1 ng/dl; range, 0.21-532, median, 315 ng/dl; range, 0.88-486, p < 0.001, respectively), in COVID-19 patients in need of intensive care compared to COVID-19 patients who did not need intensive care (median, 64.0 ng/dl; range, 0.21-337, median, 286 ng/dl; range, 0.88-532 p < 0.001, respectively), and in COVID-19 patients who died compared to survivors (median, 82.9 ng/dl; range, 2.63-165, median, 166 ng/dl; range, 0.21-532, p < 0.001, respectively). DISCUSSION AND CONCLUSION: Our data are compatible with low TT levels playing a role on the pathogenesis of the disease in Covid-19 patients with poor prognosis and a mortal course and may guide clinicians in determining the clinical course of the disease.

Does COVID-19 Worsen the Semen Parameters? Early Results of a Tertiary Healthcare Center.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is a global pandemic which may affect multiple organs and systems including testes and disrupt the gonadal functions. The current study aimed to evaluate the effect of COVID-19 on the semen parameters and sex-related hormone levels in infertile men. METHODS: The study included 21 patients who were evaluated in Ankara City Hospital, Andrology Clinic, for male infertility and have had the diagnosis of COVID-19. All the patients were evaluated in terms of semen parameters. The follicle-stimulating hormone, luteinizing hormone, and testosterone (T) levels were also evaluated in 8 of the patients. The results were presented through 2 dependent group analyses, based on the data of the patients collected before and after the diagnosis of COVID-19. RESULTS: None of the patients needed to be hospitalized at any time through the course of COVID-19. There was a significant decrease in semen volume, percentage of total motility, percentage of progressive motility, and normal sperm morphology after COVID-19 (3 [1-8] vs. 2.5 [1.5-5], p = 0.005; 48.6 ± 22.1 vs. 34.7 ± 20.7, p = 0.001; 35.1 ± 21.7 vs. 21.8 ± 15.9, p < 0.001; 6 [3-24] vs. 5 [3-18], p = 0.015; respectively). There was also a significant decline in T level of the patients after the diagnosis of COVID-19 (350.1 ± 115.5 vs. 289.8 ± 103.3, p = 0.009). CONCLUSION: COVID-19 may have unfavorable effects on the gonadal functions and may lead to further deterioration of the semen parameters in infertile men, which should be considered through the evaluation for infertility.

Testosterone Deficiency Is a Risk Factor for Severe COVID-19.

Background: Male sex is related to increased COVID-19 severity and fatality although confirmed infections are similarly distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19. Patients and Methods: We studied for effects of sex hormones on disease severity and immune activation in 377 patients (230 men, 147 women) with PCR-confirmed SARS-CoV-2 infections hospitalized at the Innsbruck University Hospital between February and December 2020. Results: Men had more severe COVID-19 with concomitant higher immune system activation upon hospital admission when compared to women. Men with a severe course of infection had lower serum total testosterone (tT) levels whereas luteinizing hormone (LH) and estradiol (E2) levels were within the normal range. tT deficiency was associated with elevated CRP (rs = - 0.567, p < 0.001), IL-6 levels (rs = - 0.563, p < 0.001), lower cholesterol levels (rs = 0.407, p < 0.001) and an increased morbidity and mortality. Men with tT levels < 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 - 144.639], p = 0.006) compared to men with tT levels > 230 ng/dL. Moreover, while morbidity and mortality showed a positive correlation with E2 levels at admission, we detected a negative correlation with the tT/E2 ratio upon hospital admission. Conclusion: Hospitalized men with COVID-19 present with rather low testosterone levels linked to more advanced immune activation, severe clinical manifestations translating into an increased risk for ICU admission or death. The underlying mechanisms remain elusive but may include infection driven hypogonadism as well as inflammation mediated cholesterol reduction causing gonadotropin suppression and impaired androgen formation. Finally, in elderly late onset hypogonadism might also contribute to lower testosterone levels.

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 (ß = -0.43; 95% CI, -0.52 to -0.17; P < .001), C-reactive protein (ß = -0.38; 95% CI, -0.78 to -0.16; P = .004), interleukin 1 receptor antagonist (ß = -0.29; 95% CI, -0.64 to -0.06; P = .02), hepatocyte growth factor (ß = -0.46; 95% CI, -0.69 to -0.25; P < .001), and interferon γ-inducible protein 10 (ß = -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.

Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients.

In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated infection (coronavirus disease 2019 [COVID-19]) developed rapidly and has turned into a global pandemic. Although SARS-CoV-2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID-19 may affect male reproductive functions. In this study, we collected semen specimens from 12 male COVID-19 patients for virus detection and semen characteristics analysis. No SARS-CoV-2 was found in semen specimens. Eight out of 12 patients had normal semen quality. We also compared the sex-related hormone levels between 119 reproductive-aged men with SARS-CoV-2 infection and 273 age-matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID-19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C-reactive protein levels in COVID-19 patients. It's the first report about semen assessment and sex-hormone evaluation in reproductive-aged male COVID-19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID-19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow-up.

Shorter androgen receptor polyQ alleles protect against life-threatening COVID-19 disease in European males.

BACKGROUND: While SARS-CoV-2 similarly infects men and women, COVID-19 outcome is less favorable in men. Variability in COVID-19 severity may be explained by differences in the host genome. METHODS: We compared poly-amino acids variability from WES data in severely affected COVID-19 patients versus SARS-CoV-2 PCR-positive oligo-asymptomatic subjects. FINDINGS: Shorter polyQ alleles (≤22) in the androgen receptor (AR) conferred protection against severe outcome in COVID-19 in the first tested cohort (both males and females) of 638 Italian subjects. The association between long polyQ alleles (≥23) and severe clinical outcome (p = 0.024) was also validated in an independent cohort of Spanish men <60 years of age (p = 0.014). Testosterone was higher in subjects with AR long-polyQ, possibly indicating receptor resistance (p = 0.042 Mann-Whitney U test). Inappropriately low serum testosterone level among carriers of the long-polyQ alleles (p = 0.0004 Mann-Whitney U test) predicted the need for intensive care in COVID-19 infected men. In agreement with the known anti-inflammatory action of testosterone, patients with long-polyQ and age ≥60 years had increased levels of CRP (p = 0.018, not accounting for multiple testing). INTERPRETATION: We identify the first genetic polymorphism that appears to predispose some men to develop more severe disease. Failure of the endocrine feedback to overcome AR signaling defects by increasing testosterone levels during the infection leads to the polyQ tract becoming dominant to serum testosterone levels for the clinical outcome. These results may contribute to designing reliable clinical and public health measures and provide a rationale to test testosterone as adjuvant therapy in men with COVID-19 expressing long AR polyQ repeats. FUNDING: MIUR project "Dipartimenti di Eccellenza 2018-2020" to Department of Medical Biotechnologies University of Siena, Italy (Italian D.L. n.18 March 17, 2020) and "Bando Ricerca COVID-19 Toscana" project to Azienda Ospedaliero-Universitaria Senese. Private donors for COVID-19 research and charity funds from Intesa San Paolo.

Severely low testosterone in males with COVID-19: A case-control study.

BACKGROUND: Circulating androgens could have a relevant pathobiological role in clinical outcomes in men with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19). OBJECTIVES: We aimed to assess: (a) circulating sex steroids levels in a cohort of 286 symptomatic men with laboratory-confirmed COVID-19 at hospital admission compared to a cohort of 281 healthy men; and (b) the association between serum testosterone levels (tT), COVID-19, and clinical outcomes. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index (CCI) was used to score health-significant comorbidities. Severe clinical outcomes were defined as patients either transferred to intensive care unit (ICU) or death. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and tT levels. Univariable and multivariable logistic regression models tested the association between tT and severe clinical outcomes. RESULTS: Overall, a significantly lower levels of LH and tT were found in patients with COVID-19 compared to healthy controls (all p < 0.0001); conversely, healthy controls depicted lower values of circulating E2 (p < 0.001). Testosterone levels suggestive for hypogonadism were observed in 257 (89.8%) patients at hospital admission. In as many as 243 (85%) cases, hypogonadism was secondary. SARS-CoV-2 infection status was independently associated with lower tT levels (p < 0.0001) and greater risk of hypogonadism (p < 0.0001), after accounting for age, BMI, CCI, and IL-6 values. Lower tT levels were associated with higher risk of ICU admission and death outcomes (all p ≤ 0.05), after accounting for clinical and laboratory parameters. CONCLUSIONS: We unveil an independent association between SARS-CoV-2 infection status and secondary hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.

COVID-19 pneumonia causes lower testosterone levels.

To evaluate the testicular damage caused by COVID-19, we prospectively evaluated 44 patients who applied to the COVID-19 outpatient clinic between March 2020 and July 2020. Patients' ages, COVID-19 PCR results, presence of pneumonia, total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) values were recorded. It was evaluated whether there were significant differences between people who were positive for COVID-19 and those who were not. Any differences between those who had COVID-19 pneumonia and those who did not were also recorded. There was no difference between the FSH, LH and testosterone values of the COVID-19 PCR positive and negative patients (p = 0.80, vp = 0.62, p = 0.56 respectively). However when LH values were separated as low, normal and high, LH values were statistically significantly higher in the COVID-19 PCR positive group (p = 0.04). Thoracic computed tomography was performed in 42 patients. Testosterone levels were significantly lower in patients with COVID-19 pneumonia (p = 0.01). When FSH, LH and testosterone values were separated as low, normal and high, there was no difference in FSH and LH values (p = 1, p = 0.2). Testosterone levels were found significantly lower in patients with COVID-19 pneumonia (p < .001). Testosterone levels seem to decrease during acute COVID-19 infection, especially in the patient group with viral pneumonia.