ABSTRACT
There has been little recognition within the medical community of the health impact of testosterone (T) deficiency (TD), also known as hypogonadism, and the substantial benefits of testosterone therapy (TTh) on health and quality of life despite high-level clinical evidence. In a roundtable symposium, investigators summarized the contemporary evidence in several key clinical areas. TD negatively impacts human health and quality of life and is associated with increased mortality. Several studies have demonstrated that TTh in men with TD reduced all-cause and cardiovascular mortality. The longstanding belief that TTh is associated with increased prostate cancer (PCa) risk is contradicted by recent evidence, including multiple studies showing that TTh is associated with reduced PCa risk. Similarly, the weight of current evidence indicates the purported concern that TTh is associated with increased cardiovascular risk is incorrect. Normalization of physiological T reduces myocardial infarction, stroke, and deaths compared with men whose testosterone levels failed to normalize. In diabetic men TTh improves insulin resistance, and a large 2-year controlled study in men with abnormal glucose tolerance showed a substantially reduced rate of diabetes among men treated with TTh compared with untreated controls. Long-term TTh in diabetic men resulted in progressive improvements in obesity and insulin requirements, including a substantial number who experienced complete remission of diabetes. Finally, TTh has been shown to reduce severe outcomes with Covid-19 infection. These lines of evidence argue strongly for the need for greater awareness in the medical community of the impact of TD on health, and of the health benefits of TTh.
ABSTRACT
There has been little recognition within the medical community of the health impact of testosterone (T) deficiency (TD), also known as hypogonadism, and the substantial benefits of testosterone therapy (TTh) on health and quality of life despite high-level clinical evidence. In a roundtable symposium, investigators summarized the contemporary evidence in several key clinical areas. TD negatively impacts human health and quality of life and is associated with increased mortality. Several studies have demonstrated that TTh in men with TD reduced all-cause and cardiovascular mortality. The longstanding belief that TTh is associated with increased prostate cancer (PCa) risk is contradicted by recent evidence, including multiple studies showing that TTh is associated with reduced PCa risk. Similarly, the weight of current evidence indicates the purported concern that TTh is associated with increased cardiovascular risk is incorrect. Normalization of physiological T reduces myocardial infarction, stroke, and deaths compared with men whose testosterone levels failed to normalize. In diabetic men TTh improves insulin resistance, and a large 2-year controlled study in men with abnormal glucose tolerance showed a substantially reduced rate of diabetes among men treated with TTh compared with untreated controls. Long-term TTh in diabetic men resulted in progressive improvements in obesity and insulin requirements, including a substantial number who experienced complete remission of diabetes. Finally, TTh has been shown to reduce severe outcomes with Covid-19 infection. These lines of evidence argue strongly for the need for greater awareness in the medical community of the impact of TD on health, and of the health benefits of TTh.
ABSTRACT
Although not universal, many epidemiological data sources signal that a higher proportion of males than females with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections have adverse outcomes, such as intensive care unit (ICU) admission and death. Though likely multifactorial, the various hypotheses that have been proposed as underlying factors behind this trend are related to greater smoking prevalence among males, testosterone (T) deficiency causing an inflammatory storm, androgen-driven pathogenesis of SARS-CoV-2, a protective effect of estrogen in females, and inborn errors of cytokine immunity. This review aims at examining the evidence and at assessing the likelihood that the factors being investigated are contributory to the reported trend of male predominance of severe COVID-19 cases. Sources were obtained using the PubMed database and were selected based on their relevance to one of the primary hypotheses attempting to explain the strong male sex bias of severe SARS-CoV-2 infections. Emphasis was placed on meta-analyses and population-based studies. Sources are current through February 22, 2022. A severe COVID-19 case or outcome is defined in this review as a progression of the SARS-CoV-2 virus that results in either admission to an ICU for management of symptoms and clinical stabilization or which leads to death. Although the trend of male predominance of severe COVID-19 cases is likely multifactorial, the hypothesis of T deficiency causing an inflammatory storm has support from many studies with limited conflicting evidence. An inborn error in cytokine immunity is also well supported, but it needs more studies to add support to the hypothesis. The immunologic protective effect of estrogen is supported by multiple studies, but it also has conflicting evidence. It appears less likely that the trend is caused solely by an increased prevalence of smoking among males or an androgen-driven pathogenesis, based on the extent of conflicting evidence.