Testosterone Deficiency, Weakness, and Multimorbidity in Men

Peterson, Mark D.; Belakovskiy, Aleksandr; McGrath, Ryan; Yarrow, Joshua F.

doi:10.1038/s41598-018-24347-6

Cited by 23 publications

(18 citation statements)

References 40 publications

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“…Although often overlooked and underdiagnosed, hypoandrogenemia is associated with visceral obesity, reduced lean body mass, T2DM, the metabolic syndrome, sexual dysfunction, impaired erectile function, and decreased quality of life . Also, testosterone deficiency has been associated with multi‐morbidity and with mortality risk .…”

Section: Introductionmentioning

confidence: 99%

Cross‐Sectional, Primary Care–Based Study of the Prevalence of Hypoandrogenemia in Nondiabetic Young Men with Obesity

Molina‐Vega

Asenjo-Plaza²,

García‐Ruiz³

et al. 2019

Obesity

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Objective Obesity‐associated hypoandrogenemia is increasing in parallel to the obesity epidemic. The prevalence of hypoandrogenemia in nondiabetic young men with obesity is not known. This study aimed to evaluate the prevalence of hypoandrogenemia and associated risk factors in this population. Methods This cross‐sectional study included 266 nondiabetic men < 50 years of age with obesity who were referred from primary care. Total testosterone (high‐performance liquid chromatography mass spectrometry), sex hormone–binding globulin, free testosterone (FT), luteinizing hormone (LH), high‐sensitivity C‐reactive protein, and homeostatic model assessment of insulin resistance were determined. Body composition and erectile function were also assessed. Hypoandrogenemia was defined as FT level < 70 pg/mL. Results Subnormal FT concentrations were found in 25.6% of participants. Hypoandrogenemia prevalence was different along the BMI continuum, being > 75% in individuals with BMI ≥ 50 kg/m2. A multivariate regression analysis indicated that increasing BMI (P < 0.001), age (P = 0.049), and reduced LH levels (P = 0.003) were independent risk factors for hypoandrogenemia. Conclusions In a primary care–based cohort of nondiabetic young men with obesity, hypoandrogenemia was a very prevalent finding and was directly associated with adiposity. Obesity, age, and reduced LH levels were independent risk factors associated with hypoandrogenemia. Further prospective studies are needed to evaluate the long‐term consequences of hypoandrogenemia in this population.

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Section: Introductionmentioning

confidence: 99%

Cross‐Sectional, Primary Care–Based Study of the Prevalence of Hypoandrogenemia in Nondiabetic Young Men with Obesity

Molina‐Vega

Asenjo-Plaza²,

García‐Ruiz³

et al. 2019

Obesity

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“…Testosterone is the most important androgen for male, exerting important physiological effects . In adult men, testosterone deficiency (TD, total testosterone <300 ng/dL is most commonly used as the cut‐off values for low testosterone) not only has adverse effects on sexual and reproductive function but also negatively affects glucose and lipid metabolism, cardiometabolic functions, body composition, bone mineral density and quality of life . The global prevalence of TD in adult men ranges from 10% to 40%; among these, the incidence in the United States varies from 24% to 39%, and it ranges from 17% to 33% in China .…”

Section: Introductionmentioning

confidence: 99%

“…1 In adult men, testosterone deficiency (TD, total testosterone <300 ng/dL is most commonly used as the cut-off values for low testosterone) 2 not only has adverse effects on sexual and reproductive function 3 but also negatively affects glucose and lipid metabolism, cardiometabolic functions, body composition, bone mineral density and quality of life. [4][5][6] The global prevalence of TD in adult men ranges from 10% to 40%; among these, the incidence in the United States varies from 24% to 39%, and it ranges from 17% to 33% in China. 2 With the economic development and life improvement, people are more and more exposed to longtime and excessive high-fat diet (HFD) and sedentary lifestyle, which could increase bodyweight, induce glucose intolerance and insulin resistance, and cause dyslipidaemia.…”

Section: Introductionmentioning

confidence: 99%

Cyclophilin D participates in the inhibitory effect of high‐fat diet on the expression of steroidogenic acute regulatory protein

Dong

Luo

et al. 2019

J Cellular Molecular Medi

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Objective The high‐fat diet (HFD)–induced obesity is responsible for the testosterone deficiency (TD). However, the mechanism remains unknown. Mitochondrial homeostasis is proved to be important for maintaining the function of steroidogenic acute regulatory protein (StAR), the first rate‐limiting enzyme in testosterone synthesis. As the key regulator of mitochondrial membrane permeability, cyclophilin D (CypD) plays a crucial role in maintaining mitochondrial function. In this study, we sought to elucidate the role of CypD in the expression of StAR affected by HFD. Methods To analyse the influence of CypD on StAR in vivo and in vitro, mouse models of HFD, CypD overexpression and CypD knockout (Ppif−/−) as well as Leydig cells treated with palmitic acid (PA) and CypD overexpression plasmids were examined with an array of metabolic, mitochondrial function and molecular assays. Results Compared with the normal diet mice, consistent with reduced testosterone in testes, the expressions of StAR in both mRNA and protein levels in HFD mice were down‐regulated, while expressions of CypD were up‐regulated. High‐fat intake impaired mitochondrial function with the decrease in StAR in Leydig cells. Overexpression of CypD inhibited StAR expressions in vivo and in vitro. Compared with C57BL/6 mice with HFD, expressions of StAR were improved in Ppif−/− mice with HFD. Conclusions Mitochondrial CypD involved in the inhibitory effect of HFD on StAR expression in testes.

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“…The prevalence of obesity in young adults is increasing at a staggering rate and is anticipated to triple within the next decade (20). A study looking at the Adolescent and Young population utilizing the National Health and Nutrition Examination Surveys (NHANES) demonstrated a statistically significant increase in BMI from 1999 to 2016.…”

Section: Etiology Of Hypogonadism In Adolescent and Young Adulthood Menmentioning

confidence: 99%

Low Testosterone in Adolescents & Young Adults

et al. 2020

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Male hypogonadism, the clinical syndrome with variable symptoms associated with gonadal dysfunction, can affect men of all ages. In older males, physiologic changes of the aging testis, account for the majority of decreased testosterone levels in this population. For younger males and adolescents, the etiology of hypogonadism is commonly due to congenital or acquired conditions that disrupt the testis production of testosterone or signaling from the hypothalamic-pituitary-gonadal axis. Diagnosis of hypogonadism in younger males can be a challenge, as symptoms such as decreased libido or erectile dysfunction, common in the older men, are not usually present, and young men instead commonly complain of low energy. While an underlying congenital cause should always be considered in young men with hypogonadism, acquired conditions such as obesity, diabetes, anabolic steroid or illicit drug use have all been associated with low testosterone levels. Outside of modifying identifiable risk factors for hypogonadism, pharmacologic testosterone therapy can also lead to therapeutic dilemmas in young men who desire paternity. Topical or injectable administration of testosterone, through negative feedback on the hypothalamus and pituitary, can decrease spermatogenesis, posing an infertility risk. Other agents that can replace testosterone or increase the body's natural production of testosterone without decreasing spermatogenesis are preferred, such as intranasal testosterone, selective estrogen modulators, aromatase inhibitors or human-chorionic gonadotrophin, often used in combination. Clinicians must maintain a high level of suspicion to properly diagnose young men with hypogonadism and tailor treatment based on both the underlying etiology and fertility goals.

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Testosterone Deficiency, Weakness, and Multimorbidity in Men

Cited by 23 publications

References 40 publications

Cross‐Sectional, Primary Care–Based Study of the Prevalence of Hypoandrogenemia in Nondiabetic Young Men with Obesity

Cross‐Sectional, Primary Care–Based Study of the Prevalence of Hypoandrogenemia in Nondiabetic Young Men with Obesity

Cyclophilin D participates in the inhibitory effect of high‐fat diet on the expression of steroidogenic acute regulatory protein

Low Testosterone in Adolescents & Young Adults

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