Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study

Al-Qudimat, Ahmad; Al‐Zoubi, Raed M.; Yassin, Aksam; Alwani, Mustafa; Aboumarzouk, Omar; Al-Rumaihi, Khaled; Talib, Raidh A.; Ansari, Abdulla Al

doi:10.1080/2090598x.2021.1959261

Cited by 11 publications

(5 citation statements)

References 75 publications

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“…Here liver parameters among KS receiving TRT were within normative ranges. Studies in hypogonadal men have also demonstrated an improvement in liver function after two years of oral testosterone or when increasing the level of testosterone [24,25]. However, the present data did show a trend towards improvement in liver function in T-KS males indicating that TRT may improve liver function in males with KS.…”

Section: Discussioncontrasting

confidence: 84%

Mild liver dysfunction in Klinefelter syndrome is associated with abdominal obesity and elevated lipids but not testosterone treatment

Øzdemir,

Ridder,

Chang

et al. 2024

J Endocrinol Invest

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Context Klinefelter syndrome (KS) is associated with hypergonadotropic hypogonadism, which contributes to characteristic phenotypical manifestations including metabolic alterations. Extensive research has demonstrated important associations between androgens and liver function. Objectives Investigation of the association between metabolic parameters, sex hormones and liver function in males with KS, both treated (T-KS) and untreated (U-KS) and healthy control males. Methods A total of 65 KS males were recruited, of which 32 received testosterone replacement therapy (TRT). Also, 69 healthy controls were recruited. We used alanine aminotransferase (ALAT), alkaline phosphatase and PP (prothrombin-proconvertin time ratio) as the main liver markers. Multivariable regression was performed within the three groups. All statistics were calculated using STATA. Principal component analysis was utilized to demonstrate the interconnected patterns among all measured biomarkers, and to elucidate how the different groups were linked to these patterns. Results Higher levels of main liver markers were observed in U-KS compared to controls, with no significant differences between U-KS and T-KS. T-KS had lower abdominal fat, total cholesterol, and LDL cholesterol than U-KS. Using multivariable models, variation in ALAT in U-KS was explained by HOMA2%S; in T-KS by BMI and SHBG; and in controls by hip circumference and estradiol. We found no multivariable models explaining variation in PP in U-KS; in T-KS, PP was explained by BMI and LDL cholesterol, and in controls by total cholesterol. Using principal component analysis U-KS was positively associated to D1 (an obese profile, which also included ALAT) and controls negatively associated with D1 (non-obese profile). Conclusion KS males have mild liver dysfunction reflected by a significant increase in the main liver markers and decrease in albumin. The presented data underscore a primary role of metabolic conditions including obesity, insulin resistance and unfavourable lipid profile, in the elevated liver function markers seen in males with KS. Whether TRT can improve liver function in KS warrants further studies. Our findings, highlight that an evaluation of the liver function should be part of the clinical care in males with KS.

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Section: Discussioncontrasting

confidence: 84%

Mild liver dysfunction in Klinefelter syndrome is associated with abdominal obesity and elevated lipids but not testosterone treatment

Øzdemir,

Ridder,

Chang

et al. 2024

J Endocrinol Invest

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“…In this study, we investigated the potential beneficial effect of testosterone on hepatic histopathological, immunological, and biochemical changes in a CCl 4 -induced mice model. Several studies have shown a relationship between testosterone and liver injury ( Al-Qudimat et al, 2021 ). Even though testosterone treatment improves liver injury and metabolic syndrome, and its effect on type two diabetes mellitus is well-documented ( Sun et al, 2021 ), testosterone effects on hepatic injury are still limited.…”

Section: Discussionmentioning

confidence: 99%

“…Advanced liver illness shares many characteristics with hypogonadal males, such as sarcopenia, osteoporosis, gynecomastia, and reduced libido ( Yurci et al, 2011 ). Al-Qudimat A et al suggest that long-term testosterone therapy in hypogonadal men improves liver function ( Al-Qudimat et al, 2021 ). However, it is not fully proven how much testosterone deprivation contributes to the symptoms of severe liver disease.…”

Section: Introductionmentioning

confidence: 99%

The immune and metabolic treatment approach of using testosterone on mice models of liver injury

Amer,

Salhab,

Snobar

et al. 2023

Front. Pharmacol.

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Background: Natural killer (NK) cells showed an anti-fibrotic effect; however, their function is thought to be impaired in advanced liver injury. In the current study, we aimed to assess the immune and metabolic impact of testosterone on mice models of liver injury.Methods: Carbon-tetrachloride induced liver fibrosis male mice models was i.p injected for 2 weeks (acute) and 4 weeks (chronic) (n = 36). Testosterone (4 mg/kg mouse body weight) was injected i.p. following the first week of the acute model of CCl4 and following the second week of the chronic model of CCl4. At the end of the experiments, mice were sacrificed, and serum was collected for assessing liver enzymes of ALT and AST, as well as inflammatory markers of IL-6, metabolic makers of C-peptide levels, and lipid and glucose profiles. Livers were harvested and used for histological assessments for inflammation and fibrosis. Fibrosis profiles from liver extracts, αSMA and Collagen III, were assessed by RT-PCR. Moreover, liver tissue-resident NK cells were isolated and evaluated for their activity by assessing INF-γ and IL-6 receptors using ELISA and flow cytometry, respectively.Results: Serum ALT, AST, and IL-6, as well as metabolic assessments of cholesterol, triglyceride, C-peptide, fasting blood sugar, and fibrotic profiles, were linearly correlated with disease progressions. Histological characterization of the liver was worsened in the chronic model of liver injury. Testosterone-treated mice exhibit a significant reduction in collagen depositions with less dense fibrosis tissue associated with reduced liver injury enzymes and metabolic markers in both the acute and chronic CCl4 mice models in favor of the latter one (p < 0.05). Moreover, testosterone treatments displayed a significant decrease in serum IL-6 of 2.4-fold (p = 0.0001) and 2.3-fold (p = 0.0003) in the acute and chronic models, respectively (p = 0.002), and data showed an increase in INF-γ release from NK associated with a reduction in their IL-6 receptor expressions (p < 0.05).Conclusion: Our results indicated effects of testosterone on mediating a decreased expressions of NK IL-6 receptors and consequently inducing their activation; which in part, could explain the amelioration of liver injury. Our data suggest an anti-inflammatory and anti-fibrotic treatment approach of using testosterone for delaying disease progressions.

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“…(•) (6). In 2 prospective studies, for 1 year (n =117) and for 8 years (n = 312), Testosterone treatment improved liver function in non-thalassemic hypogonadal males with hepatic steatosis (•) (77,78).…”

Section: Chronic Hepatitis -Liver Cirrhosismentioning

confidence: 99%

The potential benefits and risks of sex-steroids therapy in thalassemic patients with hypogonadism

Soliman¹,

Sanctis²,

Yassin³

et al. 2023

World J. Adv. Res. Rev.

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Introduction: A recent review from 14 Mediterranean and Middle East countries (n =4477, mean age = 16.5 years) showed that the pooled prevalence of delayed puberty / hypogonadism in patients with BTM was 45.6%. Studying the consequences of hypogonadism and the potential benefits versus unwanted side effects of sex-steroid hormone replacement therapy (HRT) in children and adolescents with Beta Thalassemia Major (BTM) represent an important issue for these patients. Objectives: We reviewed the literature (Pubmed, Google scholar, Scopus, Research gate) (1995: 2022) on the consequences of hypogonadism and benefits versus side effects of using sex Steroid therapy (HRT) in hypogonadal adolescents with BTM. Thirty-five papers were included and analyzed. Results: HRT had a variable but significant beneficial effect on improving bone mineral density (BMD), pubertal growth spurt, development of secondary sexual characteristics and subsequently improved quality of life (QOL) in children and adolescents with BTM. Increased side effects of HRT in these patients may occur due to their state of hypercoagulability especially in splenectomized patients and those with cardiomyopathy, chronic hepatitis, and dysglycemia. Gynecomastia and local pain in the site of injection confirmed in a considerable number of males on testosterone therapy. Local reaction to sex steroid patches appeared in around 30% of patients. Based on this review recommendations for using HRT in these patients were updated. Conclusion: Proper and wise use of sex steroid therapy in patients with BTM can significantly improve many consequences of hypogonadism.

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Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study

Cited by 11 publications

References 75 publications

Mild liver dysfunction in Klinefelter syndrome is associated with abdominal obesity and elevated lipids but not testosterone treatment

Mild liver dysfunction in Klinefelter syndrome is associated with abdominal obesity and elevated lipids but not testosterone treatment

The immune and metabolic treatment approach of using testosterone on mice models of liver injury

The potential benefits and risks of sex-steroids therapy in thalassemic patients with hypogonadism

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