COVID-19, Type 2 Diabetes, and Hypogonadism: Lessons for Acute Management and Long-Term Prevention

Abstract

Despite similar infection rates due to COVID-19 (SARS CoV-2) between men and women, male patients have twice the mortality rate across older age groups compared with women. Studies from China, Germany, and Italy suggest that there is a severe primary hypogonadism associated with acute infection and that the more severe the drop in testosterone, the higher the mortality. The co-morbidities associated with increased mortality, namely age, obesity, type 2 diabetes, chronic obstructive pulmonary disease, and chronic kidney disease are all associated with lower rates of testosterone in the general population. Longitudinal studies of testosterone therapy in these conditions have shown reduced all cause mortality. These findings suggest that screening for low testosterone and treating low levels might reduce all-cause mortality including COVID-19. Paradoxically, some observational studies in prostate cancer patients have reported lower mortality rates in those receiving androgen deprivation therapy (ADT). This has led to studies of ADT to reduce mortality associated with COVID-19 infection and suggestions that testosterone replacement therapy (TRT) should be stopped. This seems ill advised as recent publications suggest that TRT can reverse progression to type 2 diabetes and even lead to complete regression, as well as reducing all-cause mortality. In contrast, ADT has been repeatedly shown to have adverse cardio-metabolic effects with increased rates of depression, suicide and reduced quality of life. We also suggest a potentially important role for daily PDE5 inhibitors based on their established beneficial effect on endothelial dysfunction, pulmonary hypertension, insulin resistance, inflammation and cellular apoptosis.

Sex‐based differences in severity and mortality in COVID‐19

“…The authors additionally propose possible improvement in clinical outcomes with the testosterone treatment in SARS‐CoV‐2 infected hypogonadal male patients. However, due to the varying effects on different aspects of the immune system (it is not likely that testosterone's anti‐inflammatory effects would reduce all parts of immune function equally) it would be necessary to look at testosterone effects on various functions of both innate and adaptive immunity in a variety of contexts to elucidate its therapeutic potential, as well as testosterone deficiency in hypogonadism contribute to increase the risk of comorbidities such as type 2 diabetes mellitus (T2DM), and cardiovascular diseases 101–103 . Thus, increase the rate of ICU admissions and mortality in COVID‐19 patients as Cayan S et al.…”

“…Furthermore, a systemic review spotlights in the acute management of COVID‐19, T2DM and hypogonadism suggests that treating testosterone deficient COVID‐19 patients with testosterone might be considered in the future as Testosterone reduces the risk of T2DM, and boosts the body inflammatory response against the virus acutely 102 . However, further studies required in order to reveal the optimal effect of Testosterone replacement therapy.…”

“…(2020) showed that COVID‐19 patients with comorbidities have a poorer prognosis, and that greater number of comorbidities correlate to poorer clinical outcomes 2 . Specific comorbidities associated with poorer patient outcomes included chronic obstructive pulmonary disease (COPD), Obesity, diabetes, cerebrovascular disease, cancer and hypertension 2,102–104 . Globally, men have more of these morbidities than women, 105 placing them at a higher risk for severe disease.…”

Factors associated with adverse outcome among hospitalized patients with moderate to severe COVID-19

“…Половые различия в тяжести и смертности от COVID-19 многофакторные, обусловлены сопутствующими заболеваниями: хронической обструк-ИССЛЕДОВАНИЯ РЕАЛЬНОЙ КЛИНИЧЕСКОЙ ПРАКТИКИ тивной болезнью лёгких (ХОБЛ), ожирением, диабетом, цереброваскулярными заболеваниями, раком и гипертонией [7,8]. Во всём мире у мужчин таких заболеваний больше, чем у женщин [9].…”

Role of selected dietary components on the course of SARS-CoV-2 infection

“…W ciężkich postaciach choroby dochodzi do ostrej niewydolności oddechowej, przechodzącej w niewydolność wielonarządową i w ostateczności następuje zgon pacjenta. Według raportów World Health Organization (Światowa Organizacja Zdrowia, WHO) wyższą śmiertelność odnotowano u osób starszych, z chorobami współistniejącymi, takimi jak: cukrzyca, obstrukcyjna choroba płuc, choroba wieńcowa, choroby nowotworowe, nadciśnienie tętnicze, wirusowe zapalenie wątroby typu B, otyłość, przewlekła choroba nerek [7].…”