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1.
Covid-19 in Man: A Very Dangerous Affair.
Lisco, G, Giagulli, VA, De Pergola, G, De Tullio, A, Guastamacchia, E, Triggiani, V
Endocrine, metabolic & immune disorders drug targets. 2021;(9):1544-1554
Abstract
The novel pandemic of Coronavirus disease 2019 (COVID-19) has become a public health issue since March 2020, with more than 30 million people found to be infected worldwide. Men may be considered to be at a higher risk of poor prognosis or death once the infection occurred. Concerns surfaced regarding the risk of a possible testicular injury due to SARS-CoV-2 infection. Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On the one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, a younger man with normal testicular function compared to a woman of similar age is prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that the SARS-CoV-2 genome is not normally found in gonads and gametes. Therefore, transmission through sex could be excluded as a possible way to spread the COVID-19. Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection, even if it occurred asymptomatically. Still, no long-term evidence is currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.
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2.
Worse progression of COVID-19 in men: Is testosterone a key factor?
Giagulli, VA, Guastamacchia, E, Magrone, T, Jirillo, E, Lisco, G, De Pergola, G, Triggiani, V
Andrology. 2021;(1):53-64
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Abstract
BACKGROUND The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease 2019 (COVID-19) seems to have a worse clinical course among infected men compared with women, thus highlighting concerns about gender predisposition to serious prognosis. Therefore, androgens, particularly testosterone (T), could be suspected as playing a critical role in driving this excess of risk. However, gonadal function in critically ill men is actually unknown, mainly because serum T concentration is not routinely measured in clinical practice, even more in this clinical context. OBJECTIVE To overview on possible mechanisms by which serum T levels could affect the progression of COVID-19 in men. METHODS Authors searched PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, Google, and institutional websites for medical subject headings terms and free text words referred to "SARS-CoV-2," "COVID-19," "testosterone," "male hypogonadism," "gender" "immune system," "obesity," "thrombosis" until May 19th 2020. RESULTS T, co-regulating the expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2 in host cells, may facilitate SARS-CoV-2 internalization. Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation. Obesity, one of the leading causes of severe prognosis in infected patients, is strictly associated with functional hypogonadism, and may consistently strengthen the aforementioned alterations, ultimately predisposing to serious respiratory and systemic consequences. DISCUSSION AND CONCLUSION T in comparison to estrogen may predispose men to a widespread COVID-19 infection. Low serum levels of T, which should be supposed to characterize the hormonal milieu in seriously ill individuals, may predispose men, especially elderly men, to poor prognosis or death. Further studies are needed to confirm these pathophysiological assumptions and to promptly identify adequate therapeutic strategies.
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Monitoring Blood Biomarkers and Training Load Throughout a Collegiate Soccer Season.
Huggins, RA, Fortunati, AR, Curtis, RM, Looney, DP, West, CA, Lee, EC, Fragala, MS, Hall, ML, Casa, DJ
Journal of strength and conditioning research. 2019;(11):3065-3077
Abstract
Huggins, RA, Fortunati, AR, Curtis, RM, Looney, DP, West, CA, Lee, EC, Fragala, MS, Hall, ML, and Casa, DJ. Monitoring blood biomarkers and training load throughout a collegiate soccer season. J Strength Cond Res 33(11): 3065-3077, 2019-This observational study aimed to characterize the responses of a comprehensive panel of biomarkers, observed ranges, training load (TL) metrics, and performance throughout the collegiate soccer season (August-November). Biomarkers (n = 92) were collected before the start of pre-season (PS), in-season weeks (W)1, W4, W8, and W12 in NCAA Division I male soccer players (n = 20, mean ± SD; age = 21 ± 1 years, height = 180 ± 6 cm, body mass = 78.19 ± 6.3 kg, body fat = 12.0 ± 2.6%, VO2max 51.5 ± 5.1 ml·kg·min). Fitness tests were measured at PS, and W12 and TL was monitored daily. Changes in biomarkers and performance were calculated via separate repeated-measures analysis of variance. Despite similar fitness (p > 0.05), endocrine, muscle, inflammatory, and immune markers changed over time (p < 0.05). Total and free testosterone was lower in W1 vs. PS, whereas free cortisol remained unchanged at PS, W1, and W4 (>0.94 mg·dL). Oxygen transport and iron metabolism markers remained unchanged except for HCT (W1 vs. PS) and total iron binding capacity (W8-W12 vs. W1). Hepatic markers albumin, globulin, albumin:globulin, and total protein levels were elevated (p < 0.05) at W12 vs. W1, whereas aspartate aminotransferase and alanine aminotransferase levels were elevated at W1-W12 and W8-W12 vs. PS, respectively. Vitamin E, zinc, selenium, and calcium levels were elevated (p < 0.05) at W12 vs. W1, whereas Vitamin D was decreased (p < 0.05). Fatty acids and cardiovascular markers (omega-3 index, cholesterol:high-density lipoprotein [HDL], docosahexenoic acid, low-density lipoprotein [LDL], direct LDL, non-HDL, ApoB) were reduced at W1 vs. PS (p ≤ 0.05). Immune, lipid, and muscle damage biomarkers were frequently outside clinical reference ranges. Routine biomarker monitoring revealed subclinical and clinical changes, suggesting soccer-specific reference ranges. Biomarker monitoring may augment positive adaptation and reduce injuries from stressors incurred during soccer.
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Salivary testosterone and immunoglobulin A were increased by resistance training in adults with Down syndrome.
Fornieles, G, Rosety, MA, Elosegui, S, Rosety, JM, Alvero-Cruz, JR, Garcia, N, Rosety, M, Rodriguez-Pareja, T, Toro, R, Rosety-Rodriguez, M, et al
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2014;(4):345-8
Abstract
This study was designed to assess the influence of resistance training on salivary immunoglobulin A (IgA) levels and hormone profile in sedentary adults with Down syndrome (DS). A total of 40 male adults with DS were recruited for the trial through different community support groups for people with intellectual disabilities. All participants had medical approval for participation in physical activity. Twenty-four adults were randomly assigned to perform resistance training in a circuit with six stations, 3 days per week for 12 weeks. Training intensity was based on functioning in the eight-repetition maximum (8RM) test for each exercise. The control group included 16 age-, gender-, and BMI-matched adults with DS. Salivary IgA, testosterone, and cortisol levels were measured by ELISA. Work task performance was assessed using the repetitive weighted-box-stacking test. Resistance training significantly increased salivary IgA concentration (P=0.0120; d=0.94) and testosterone levels (P=0.0088; d=1.57) in the exercising group. Furthermore, it also improved work task performance. No changes were seen in the controls who had not exercised. In conclusion, a short-term resistance training protocol improved mucosal immunity response as well as salivary testosterone levels in sedentary adults with DS.
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[Physical activity for primary prevention of prostate cancer. Possible mechanisms].
Heitkamp, HC, Jelas, I
Der Urologe. Ausg. A. 2012;(4):527-32
Abstract
BACKGROUND An explanation of the possible connection between physical activity and prevention of prostate cancer was sought by reviewing the controversial data from prospective and case-control studies. Possible preventive mechanisms are to be described. METHOD Scientific publications mainly from the past 10 years were reviewed. RESULTS Because of the postulated dependence of prostate carcinoma on testosterone, lowering the testosterone concentration by physical activity is of importance and seems to be a possible explanation. According to many studies there is a speculative connection between prostate carcinoma and calcium concentration in blood, parathormone and vitamin D(3), and the possibly preventive modulation by physical activity results in another beneficial mechanism. Less specific is the possible increase of the antioxidant capacity of the organism by physical activity. Strength training seems to have adverse effects on testosterone, while possibly yielding a beneficial effect on the immune system. CONCLUSION High intensive physical activity may contribute to the prevention of prostate carcinoma.
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Effects of testosterone administration in human immunodeficiency virus-infected women with low weight: a randomized placebo-controlled study.
Dolan, S, Wilkie, S, Aliabadi, N, Sullivan, MP, Basgoz, N, Davis, B, Grinspoon, S
Archives of internal medicine. 2004;(8):897-904
Abstract
BACKGROUND The prevalence of human immunodeficiency virus (HIV) disease is increasing among women, many of whom remain symptomatic with low weight and poor functional status. Although androgen levels may often be reduced in such patients, the safety, tolerability, and efficacy of testosterone administration in this population remains unknown. METHODS A total of 57 HIV-infected women with free testosterone levels less than the median of the reference range and weight less than 90% of ideal body weight or weight loss greater than 10% were randomly assigned to receive transdermal testosterone (4 mg/patch) twice weekly or placebo for 6 months. Muscle mass was assessed by urinary creatinine excretion. Muscle function was assessed by the Tufts Quantitative Muscle Function Test. Treatment effect at 6 months was determined by analysis of covariance. Results are mean +/- SEM unless otherwise specified. RESULTS At baseline, subjects were low weight (body mass index [calculated as weight in kilograms divided by the square of height in meters] 20.6 +/- 0.4), with significant weight loss from pre-illness maximum weight (18.7% +/- 1.2%), and demonstrated reduced muscle function (upper and lower extremity muscle strength, 83% and 67%, respectively, of predicted range). Testosterone treatment resulted in significant increases in testosterone levels vs placebo (total testosterone: 37 +/- 5 vs -2 +/- 2 ng/dL [1.3 +/- 0.2 vs -0.1 +/- 0.1 nmol/L] [P<.001]; free testosterone: 3.7 +/- 0.5 vs -0.4 +/- 0.3 pg/mL [12.8 +/- 1.7 vs -1.4 vs 1.0 pmol/L] [P<.001]) and was well tolerated, without adverse effects on immune function, lipid and glucose levels, liver function, or body composition or the adverse effect of hirsutism. Muscle mass tended to increase (1.4 +/- 0.6 vs 0.3 +/- 0.8 kg; P =.08), and shoulder flexion (0.4 +/- 0.3 vs -0.5 +/- 0.3 kg; P =.02), elbow flexion (0.3 +/- 0.4 vs -0.7 +/- 0.4 kg; P =.04), knee extension (0.2 +/- 1.0 vs -1.7 +/- 1.3 kg; P =.02), and knee flexion (0.7 +/- 0.5 vs 0.3 +/- 0.7 kg; P =.04) increased in the testosterone-treated compared with the placebo-treated subjects. CONCLUSIONS Testosterone administration is well-tolerated and increases muscle strength in low-weight HIV-infected women. Testosterone administration may be a useful adjunctive therapy to maintain muscle function in symptomatic HIV-infected women.
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7.
The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men.
Malkin, CJ, Pugh, PJ, Jones, RD, Kapoor, D, Channer, KS, Jones, TH
The Journal of clinical endocrinology and metabolism. 2004;(7):3313-8
Abstract
Testosterone has immune-modulating properties, and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha, IL-1beta, and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10. We report a randomized, single-blind, placebo-controlled, crossover study of testosterone replacement (Sustanon 100) vs. placebo in 27 men (age, 62 +/- 9 yr) with symptomatic androgen deficiency (total testosterone, 4.4 +/- 1.2 nmol/liter; bioavailable testosterone, 2.4 +/- 1.1 nmol/liter). Compared with placebo, testosterone induced reductions in TNFalpha (-3.1 +/- 8.3 vs. 1.3 +/- 5.2 pg/ml; P = 0.01) and IL-1beta (-0.14 +/- 0.32 vs. 0.18 +/- 0.55 pg/ml; P = 0.08) and an increase in IL-10 (0.33 +/- 1.8 vs. -1.1 +/- 3.0 pg/ml; P = 0.01); the reductions of TNFalpha and IL-1beta were positively correlated (r(S) = 0.588; P = 0.003). In addition, a significant reduction in total cholesterol was recorded with testosterone therapy (-0.25 +/- 0.4 vs. -0.004 +/- 0.4 mmol/liter; P = 0.04). In conclusion, testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol. Twenty of these men had established coronary disease, and because total cholesterol is a cardiovascular risk factor, and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque, these properties may have particular relevance in men with overt vascular disease.