SARS-CoV-2 Pneumonia Affects Male Reproductive Hormone Levels: A Prospective, Cohort Study

Abstract

Background: SARS-CoV-2 which causes coronavirus disease 2019 binds to angiotensinconverting enyzme 2 (ACE2) and enters the host cell. ACE2 protein is expressed highly in the testis. Aim: The aim of this study was to compare male reproductive hormones such as total testosterone (TT), luteinizing hormone (LH), follicular stimulant hormone (FSH), and prolactin between patients with COVID-19, age-matched cases with noneCOVID-19 respiratory tract infection, and age-matched controls. Methods: This was a prospective cohort study and included 262 men aged between 20 and 65 years. The study comprised 3 groups including patients with COVID-19 (n ¼ 89), cases with noneCOVID-19 respiratory tract infection (n ¼ 30), and age-matched controls (n ¼ 143). All cases were evaluated using TT, LH, FSH, and prolactin. Correlations between TT and clinical parameters of patient groups were investigated using Pearson's correlation test. Outcomes: The primary outcome of the study was detection of the difference of TT, FSH, LH, and prolactin levels between the groups. Secondary outcome was to correlate TT and hospitalization time and oxygen saturation on hospital admission (SpO2) of patients. Results: The mean age of study groups was 49.9 ± 12.5 years, 52.7 ± 9.6 years, and 50 ± 7.8 years, respectively (P ¼ .06). Serum TT levels was median 185.52 ng/dL in patients with COVID-19, median 288.67 ng/dL in patients with noneCOVID-19 respiratory tract infection and median 332 ng/dL in control cases, (P < .0001). The proportion of patients with testosterone deficiency in group 1, group 2, and group 3 was 74.2%, 53.3%, and 37.8%, respectively (P < .0001). Serum LH levels (P ¼ 0.0003) and serum prolactin levels (P ¼ .0007) were higher in patients with COVID-19 and patients with noneCOVID-19 respiratory tract infection than control cases. Correlation analysis revealed significant negative correlation between serum TT levels and hospitalization time of patients with COVID-19 (r ¼ e0.45, P < .0001). In addition, a significant positive correlation was observed between SpO2 and serum TT levels in patients with COVID-19 ( r ¼ 0.32, P ¼ .0028). Clinical Implications: Physicians may consider to evaluate male patients with COVID-19 for concomitant androgen deficiency. Strengths & Limitations: Strengths include the evidence about the alteration of male reproductive hormones under COVID-19. Limitations include the analysis limited to one general hospital, only a single measurement of TT was available, free and bioavailable testosterone levels were not evaluated. Conclusion:This study demonstrates COVID-19 is associated with decreased level of TT and increased level of LH and prolactin. More serious COVID-19 causes more reduction in TT levels and prolongs hospitalization period.

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

“…Çayan et al 30 showed that COVID‐19 could decrease circulating T levels, and lower T levels at baseline were associated with a significantly increased risk in terms of ICU and mortality. Similarly, Kadihasanoglu et al recently reported the findings of a prospective cohort study where male patients with COVID‐19 have been compared with men with non‐COVID‐19 respiratory tract infection and age‐matched controls; interestingly enough, testosterone deficiency was found in almost 74% of men with COVID‐19, and serum tT levels were significantly correlated with a longer hospitalization time 31 …”

“Mask up to keep it up”: Preliminary evidence of the association between erectile dysfunction and COVID‐19

“…42 The testicular injury reported in these studies could also be a consequence of alterations in the coagulative status, resulting in development of ischemia at a microvascular level. 43 Independently of the etiology, testicular damage can possibly lead to the development of a form of hypergonadotropic hypogonadism [44][45][46][47][48] : As testosterone modulates endothelial function, 49 the possible effects of COVID-19 on erection could also be indirectly due to impaired testosterone secretion from the affected testis, besides the known direct effects of testosterone in male sexual response. 50 Additionally, as higher testosterone levels are also associated with lower levels of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukins (IL-6 and IL-1β), and higher levels of anti-inflammatory cytokines (such as IL-10), 51 the "immunothrombotic" mechanism described for COVID-19 52 and involving the same cytokines 5,53 could be promoted by the hypogonadal state encountered in affected patients.…”

Late Impact of COVID-19 Pneumonia on Testosterone Levels in Recovered, Post-Hospitalized Male Patients

“…Lower testosterone and higher LH levels in comparison of active COVID-19 patients with age-matched healthy controls were reported [8,17,18]. Similarly, male patients with COVID-19 had lower testosterone levels even in comparison with non-COVID-19 respiratory tract infections and age-matched controls [19]. This may point to a specific pathogenic impact on testicular functions rather than acute phase hypogonadism [20].…”

“…Furthermore, testosterone could predict the outcomes of hospitalized COVID-19 patients. Hypotestosteronemia was linked with increased risk in terms of ICU and mortality [19], need of mechanical ventilation or mortality [17], and higher risk of ICU admission and death outcomes [21]. Moreover, testosterone levels were significantly associated with a longer time of hospitalization [19].…”

“…Few studies reported abnormally elevated prolactin COVID-19 Impact on Testosterone J Endocrinol Metab. 2021;11 (3)(4):76-82 levels in COVID-19 pneumonia which has a known suppressive effect on pituitary gonadotropin secretion although hyperprolactinemia might be attributed to other etiologies like drugs and stress [19,23,24]. Furthermore, direct damage of testicular tissue by the SARS-CoV-2 virus was hypothesized.…”