Epicardial fat: the role of testosterone and lipid metabolism in a cohort of patients with Klinefelter syndrome

Granato, S.; Bárbaro, Giuseppe; Giorgio, Maria Rosaria Di; Rossi, Fábio; Marzano, C.; Impronta, Flavia; Spaziani, Matteo; Anzuini, Antonella; Lenzi, Andrea; Radicioni, A.

doi:10.1016/j.metabol.2019.03.002

Cited by 12 publications

(3 citation statements)

References 29 publications

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“…28,58,[60][61][62][63] In a series of 221 men with KS and 77 age-matched controls, epicardial fat thickness (EFT), a cardiac marker of visceral adiposity, was similar in hypogonadal KS men and in either KS men under TRT or obese controls, suggesting that KS itself and BMI represent the major determinants of EFT, independently from androgenic status. 64 In a recent randomized, double-blind, placebocontrolled, BMI-matched, cross-over study on 13 men with KS, TRT did not affect insulin sensitivity, as assessed by euglycemic clamp. 65 Taken together these findings point to a genetic, rather than hormonal basis, of KS-associated metabolic derangements.…”

Section: Discussionmentioning

confidence: 94%

Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study

Barbonetti

D’Andrea

Vena

et al. 2021

The Journal of Sexual Medicine

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Background Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS). Aim To define pooled prevalence estimates and correlates of erectile dysfunction (ED) and decreased libido (DL) in KS. Methods A thorough search of Medline, Embase and Web of Science was performed to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effect models and the between-studies heterogeneity was assessed by the Cochrane’s Q and I2. The sources of heterogeneity were investigated by meta-regression and sub-group analyses. Funnel plot, Begg’s rank correlation and trim-and-fill test were used to assess publication bias. Main Outcome Measure The pooled prevalence of ED and DL in KS as well as 95% confidence intervals (CIs) were estimated from the proportion of cases of sexual dysfunction and the sample size. Variables that could affect the estimates were identified by linear meta-regression models. RESULTS Sixteen studies included collectively gave information about ED and DL in 482 and 368 KS men, respectively, resulting in a pooled prevalence of 28% (95% CI: 19%–36%) for ED and 51% (95% CI: 36%–66%) for DL, with a large heterogeneity. The trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimates. At the meta-regression analyses, a higher prevalence of ED was significantly associated with an older age but not with lower testosterone levels. In series with a mean age >35 years, the ED prevalence estimate increased up to 38% (95% CI: 31%–44%) with no heterogeneity (I2=0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age. Clinical Implications While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels. Strength & Limitations This is the first meta-analysis defining pooled prevalence estimates and correlates of ED and DL in KS. Nevertheless, caution is required when interpreting results, due to the high risk of bias in many studies, as well as the dearth of data about psychosocial and/or psychosexological variables and age at the diagnosis. CONCLUSIONS ED and DL represent common clinical complaints in KS. While the prevalence of ED would increase with age, DL gets more common as serum testosterone decreases. Further studies are warranted to elucidate the pathogenetic mechanism(s) underlying the age-dependent increase in the prevalence of ED, apparently unrelated to the androgenic status.

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Section: Discussionmentioning

confidence: 94%

Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study

Barbonetti

D’Andrea

Vena

et al. 2021

The Journal of Sexual Medicine

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“…The intra-and inter-assay coefficients of variation were 3.1 and 4.7% at 3.2 IU/L (FSH), 3.6 and 5.1% at 3.3 IU/L (LH) and 2.1 and 3.6% at 10.08 nmol/L (T). The normal ranges for prepubertal subjects (i.e., all subjects included in the study) were < 0.05-2.00 IU/L (FSH), < 0.07-1.80 IU/L (LH) and < 0.28-2.2 nmol/L (T) [24][25][26]. Serum INHB was measured using an enzymatically amplified two-site two-step sandwich-type immunoassay (ELISA) (Beckman Coulter, Inc. Brea CA, USA).…”

Section: Hormone Analysismentioning

confidence: 99%

Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study

Spaziani

Tarantino

Pozza

et al. 2020

J Endocrinol Invest

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Purpose Higher grade aneuploidies (HGAs) of the male sex chromosomes are a rare genetic group of pathologies caused by nondisjunction meiotic events. The aim of this study was to evaluate the impact of early androgenic therapy on the testicular secretory hormone profile, and the pathophysiological implications. Patients and methods In this cross-sectional study, 18 HGA subjects aged 6–8 years were recruited. They were divided into two groups, based on whether or not they had previously undergone testosterone therapy (group 1: 11 untreated subjects; group 2: 7 treated subjects). Serum FSH, LH, testosterone (T), inhibin B (INHB) and anti-Müllerian hormone (AMH) were determined, and auxological parameters were assessed. Five group 1 patients and four group 2 patients were treated with hCG (human chorionic gonadotropin) for inguinal cryptorchidism; their hormone profile and auxological parameters were assessed both pre- and post-hCG treatment. Results Group 1 subjects showed significantly higher testicular volume and higher levels of AMH and INHB (p < 0.0001). Subjects who had undergone hCG therapy showed a significantly higher testicular volume, penis length (respectively, p = 0.008 and p = 0.0005 for group 1 and p = 0.04 and p = 0.001 for group 2) and T (p = 0.005 for group 1 and p = 0.004 for group 2). Conclusions HGA patients undergoing early testosterone therapy show an earlier and persistent suppression of testicular secretory function. At this age, the testes are still responsive to stimulation with hCG. The selection of patients to be treated must be accompanied by a thorough clinical and hormonal evaluation.

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“…1 Phenotypically, this additional X chromosome has a wide variety of effects on the affected individuals, but nearly all adults with XXY have testicular insufficiency resulting in hypogonadism and infertility. 2 Additionally, adults with XXY have a higher risk of metabolic syndrome and type 2 diabetes, [2][3][4][5][6] and cardiovascular diseases (CVD) are the leading cause of death in men with XXY. [7][8][9] Due to the universal testicular dysfunction associated with XXY, it is presumed that hypogonadism contributes to this increased CVD risk; however, the mechanisms are elusive.…”

Section: Introductionmentioning

confidence: 99%

In-vivo Skeletal Muscle Mitochondrial Function in Klinefelter Syndrome

Cung

Pyle

Nadeau

et al. 2022

Journal of Investigative Medicine

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Klinefelter syndrome (XXY) occurs in 1 in 600 males, resulting in testosterone deficiency and a high prevalence of insulin resistance. Testosterone deficiency in men is a known cause of insulin resistance, and mitochondrial dysfunction is hypothesized to mediate this relationship. The aim of this cross-sectional study was to evaluate muscle mitochondrial function in XXY compared with male controls. Twenty-seven boys with XXY (age 14.7±1.8 years) were compared with 87 controls (age 16.9±0.9). In-vivo calf muscle mitochondrial function was assessed via phosphorus magnetic resonance spectroscopy (31P-MRS) following 90 s of isometric 70% maximal exercise. Multiple linear regression was used to compare 31P-MRS outcomes (ADP and phosphocreatine (PCr) time constants, rate of oxidative phosphorylation (Oxphos), and Qmax or the maximal mitochondrial function relative to mitochondrial density) between groups after adjusting for age differences. There were no statistically significant differences in the mitochondrial outcomes of ADP, Oxphos, PCr, and Qmax between the groups. There were also no differences in a sensitivity analysis within the XXY group by testosterone treatment status. In this study, in-vivo postexercise skeletal muscle mitochondrial function does not appear to be impaired in adolescents with XXY compared with controls and is not significantly different by testosterone treatment status in XXY.

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Epicardial fat: the role of testosterone and lipid metabolism in a cohort of patients with Klinefelter syndrome

Cited by 12 publications

References 29 publications

Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study

Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study

Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study

In-vivo Skeletal Muscle Mitochondrial Function in Klinefelter Syndrome

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