Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2<scp>DM</scp>: a meta‐analysis of randomized controlled trials

Zhang, Kun; Zhao, Ming; An, Qi; Jia, Yuan; Fu, Lilan; Xu, Jie; Gu, Yiqun

doi:10.1111/andr.12425

Cited by 15 publications

(10 citation statements)

References 62 publications

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“…The authors concluded that the clinical significance of these changes is uncertain (Mohler et al ., 2018). A recent meta‐analysis of clinical studies of testosterone treatment in hypogonadal men (defined as total testosterone < 12 mmol/L) with T2DM included seven studies (total n = 612 men), 5 of which were RCTs (Zhang et al ., 2018). Again, a slight reduction in total cholesterol (−0.17 mmol/L) was reported, but in contrast to the T‐trials, testosterone treatment was associated with a significant reduction in triglyceride concentrations (−0.32 mmol/L).…”

Section: Metabolic Impact Of Testosterone Treatment In Clinical Trialsmentioning

confidence: 99%

“…Again, a slight reduction in total cholesterol (−0.17 mmol/L) was reported, but in contrast to the T‐trials, testosterone treatment was associated with a significant reduction in triglyceride concentrations (−0.32 mmol/L). Effects on HDL and LDL cholesterol were not significant in this meta‐analysis (Zhang et al ., 2018). In the aforementioned meta‐analysis by Corona, if only men with a baseline testosterone < 12 nmol/L were considered, similar reductions in total cholesterol (−0.35 mmol/L) and triglycerides (−0.22 mmol/L) were observed, and again, no effect on HDL or LDL cholesterol (Corona et al ., 2016).…”

Section: Metabolic Impact Of Testosterone Treatment In Clinical Trialsmentioning

confidence: 99%

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Late‐onset hypogonadism: metabolic impact

2019

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Background Obesity and dysglycemia (comprising insulin resistance, the metabolic syndrome and type 2 diabetes), that is diabesity, are associated with reduced circulating testosterone and, in some men, clinical features consistent with androgen deficiency. Objective To review the metabolic impact of late‐onset hypogonadism. Methods Comprehensive literature search with emphasis on recent publications. Results Obesity is one of the strongest modifiable risk factors for late‐onset hypogonadism, and coexisting diabetes leads to further hypothalamic‐pituitary‐testicular axis suppression. The hypothalamic‐pituitary‐testicular axis suppression is functional and hence potentially reversible, and occurs predominantly at the level of the hypothalamus. While definitive mechanistic data are lacking, the evidence suggests that hypothalamic‐pituitary‐testicular axis suppression is mediated by dysregulation of pro‐inflammatory cytokines leading to hypothalamic inflammation. Dysregulation of central leptin and insulin signaling may also contribute. In contrast, recent data challenge the paradigm that estradiol excess is a major contributor to hypothalamic‐pituitary‐testicular axis suppression. Instead, relative estradiol signaling deficiency may contribute to metabolic dysregulation in men with diabesity. While weight loss and optimization of comorbidities can reverse functional hypothalamic‐pituitary‐testicular axis suppression, testosterone treatment leads to metabolically favorable changes in body composition and to improvements in insulin resistance. Discussion The relationship between diabesity and late‐onset hypogonadism is bidirectional. Preliminary evidence suggests that, in carefully selected men, lifestyle measures and testosterone treatment may have additive effects. Conclusions While recent research has provided new insights into mechanistic and clinical aspects of diabesity‐associated late‐onset hypogonadism, more evidence from well‐designed large trials is needed to guide the optimal clinical approach to such men.

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Section: Metabolic Impact Of Testosterone Treatment In Clinical Trialsmentioning

confidence: 99%

Section: Metabolic Impact Of Testosterone Treatment In Clinical Trialsmentioning

confidence: 99%

Late‐onset hypogonadism: metabolic impact

2019

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“…Numerous studies have documented that androgen deficiencies and dysregulation of iron homeostasis are common features observed in obese men [1][2][3]. In Taiwan, one in two men is either overweight or obese [4], and one-fourth of Taiwanese men have an androgen deficiency (24.1%) (total testosterone (T) of <300 ng/dL or free T of <5 ng/dL) [5] and iron overload (21.5%) (serum ferritin>300ng/mL) [6,7].…”

Section: Introductionmentioning

confidence: 99%

Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity

et al. 2020

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The literature suggests a bidirectional relationship between testosterone (T) and iron, but mechanisms underlying this relationship remain unclear. We investigated effects of iron on advanced glycation end products (AGEs) in obesity-related androgen deficiency. In total, 111 men were recruited, and iron biomarkers and N(ɛ)-(carboxymethyl)lysine (CML) were measured. In an animal study, rats were fed a 50% high-fat diet (HFD) with (0.25, 1, and 2 g ferric iron/kg diet) or without ferric citrate for 12 weeks. Obese rats supplemented with >1 g iron/kg diet had decreased testicular total T compared to HFD alone. Immunohistochemical staining showed that >1 g of ferric iron increased iron and AGE retention in testicular interstitial tissues, which is associated with increased expression of the receptor for AGEs (RAGE), tumor necrosis factor-α, and nitric oxide. Compared with normal weight, overweight/obese men had lower T levels and higher rates of hypogonadism (19% vs. 11.3%) and iron overload (29.8% vs.15.9%). A correlation analysis showed serum total T was positively correlated with transferrin saturation (r = 0.242, p = 0.007) and cathepsin D (r = 0.330, p = 0.001), but negatively correlated with red blood cell aggregation (r = −0.419, p<0.0001) and CML (r = −0.209, p < 0.05). In conclusion, AGEs may partially explain the underlying relationship between dysregulated iron and T deficiency.

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“…Studies on the effect of TRT on HDL concentration yielded conflicting result with either a decrease [152] or no changes [102,153]. Other investigators observed an increase in concentration of HDL level after testosterone administration [154]. In a recent study on the effects of TRT on lipid metabolism in hypogonadal men with T2DM, it has been hypothesized that because the relationship between lipid metabolism and artherosclerosis are unequivocal, TRT, which ameliorates lipid metabolism, may decrease the morbidity and mortality of CVD in hypogonadal men with T2DM by preventing atherogenesis [155].…”

Section: Testosterone Replacement Therapy In Cvd Patientsmentioning

confidence: 99%

Role of Androgens in Cardiovascular Diseases in Men: A Comprehensive Review

Mukherjee¹,

Sen²,

Gupta³

et al. 2020

Chemistry and Biological Activity of Steroids

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The present knowledge on the androgens role in cardiovascular physiology is not fully completed. It remains unclear whether low serum testosterone concentrations in men are an independent risk factor for cardiovascular diseases (CVDs) or a marker of the presence of CVD. However, we demonstrated that endogenous testosterone levels may be implicated in CVDs. Androgens role in modulating cardiovascular function is one of the highest importances, given that its deficiency is strongly associated with hypertension, atherosclerosis, diabetes, obesity, and cardiac hypertrophy. Although significant and independent association between testosterone levels and cardiovascular events in elderly men have not been confirmed in large prospective studies, cross-sectional studies, however, suggested that low testosterone levels in elderly men are associated with CVDs. The results of androgen therapy are not also conclusive. Perhaps, the effects of testosterone treatment of cardiovascular mortality and morbidity have not been extensively examined in control studies. Data on male animal experimentation of the effect of testosterone replacement therapy are either neutral or beneficial on the development of atherosclerosis. Since circulatory androgen levels modulation is expected to cause many other side effects, it seems to be essential to develop a strategy to target androgen receptor for better treating the CVDs.

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Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2DM: a meta‐analysis of randomized controlled trials

Cited by 15 publications

References 62 publications

Late‐onset hypogonadism: metabolic impact

Late‐onset hypogonadism: metabolic impact

Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity

Role of Androgens in Cardiovascular Diseases in Men: A Comprehensive Review

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