Sarcopenia is associated with reduced quality of life and premature mortality. The sex disparities in the processes underlying sarcopenia pathogenesis, which include mitochondrial dysfunction, are ill-understood and can be decisive for the optimization of sarcopenia-related interventions. To improve the knowledge regarding the sex differences in skeletal muscle aging, the gastrocnemius muscle of young and old female and male rats was analyzed with a focus on mitochondrial remodeling through the proteome profiling of mitochondria-enriched fractions. To the best of our knowledge, this is the first study analyzing sex differences in skeletal muscle mitochondrial proteome remodeling. Data demonstrated that age induced skeletal muscle atrophy and fibrosis in both sexes. In females, however, this adverse skeletal muscle remodeling was more accentuated than in males and might be attributed to an age-related reduction of 17beta-estradiol signaling through its estrogen receptor alpha located in mitochondria. The females-specific mitochondrial remodeling encompassed increased abundance of proteins involved in fatty acid oxidation, decreased abundance of the complexes subunits, and enhanced proneness to oxidative posttranslational modifications. This conceivable accretion of damaged mitochondria in old females might be ascribed to low levels of Parkin, a key mediator of mitophagy. Despite skeletal muscle atrophy and fibrosis, males maintained their testosterone levels throughout aging, as well as their androgen receptor content, and the age-induced mitochondrial remodeling was limited to increased abundance of pyruvate dehydrogenase E1 component subunit beta and electron transfer flavoprotein subunit beta. Herein, for the first time, it was demonstrated that age affects more severely the skeletal muscle mitochondrial proteome of females, reinforcing the necessity of sex-personalized approaches towards sarcopenia management, and the inevitability of the assessment of mitochondrion-related therapeutics. 

Mitochondrial remodeling underlying age-induced skeletal muscle wasting: let's talk about sex.

To describe changes in homeostasis model assessment of insulin resistance index (HOMA‐IR) following testosterone therapy in men with hypogonadism and metabolic syndrome (MetS).

Testosterone therapy reduces insulin resistance in men with adult-onset testosterone deficiency and metabolic syndrome. Results from the Moscow Study, a randomized controlled trial with an open-label phase.

Background There is insufficient attention to hypogonadism in Chinese males with type 2 diabetes mellitus (T2DM). We evaluated the relationship between Combined obesity- and lipid-related indices [Visceral Adiposity Index (VAI), Chinese Visceral Adiposity Index (CVAI), Triglyceride Glucose Index (TyG) and Lipid Accumulation Product (LAP)] with total testosterone (TT) and analyzed the predictive capability of the respective cut-off values. Methods We recruited 958 hospitalized male patients with T2DM at the Affiliated Hospital of Qingdao University, collected baseline data and four calculated indices, and obtained their dominance ratio (OR) and corresponding 95% confidence intervals (CI) with TT by multivariate logistic regression. Receiver operating characteristic (ROC) curves were then used to determine cutoff values in predicting hypogonadism (TT< 12 nmol/L), and we also analyzed the combinations between the different indices. Results VAI, CVAI, TyG, and LAP all have satisfactory predictive capabilities. The test capability (sensitivity and specificity) of all four indices was better or not worse than that of body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and waist circumference (WC). All four indices were effective predictors of hypogonadism at their respective cutoff values (VAI ≥ 2.284, CVAI ≥ 145.779, TyG ≥ 4.308, and LAP ≥ 59.850). Of these, LAP had the largest area under the curve (AUC, AUC = 0.852, Std. Error = 0.014, 95% CI = 0.818-0.873). However, the predictive capability of the combined indices was not significantly improved over the individual indices. Conclusions VAI, CVAI, TyG, and LAP are sensitive indices for predicting hypogonadism in Chinese male patients with T2DM. Considering the need for concise and accurate indices in clinical practice, we suggest LAP as a commonly used index.

Combined obesity- and lipid-related indices are associated with hypogonadism in Chinese male patients with type 2 diabetes: a cross-sectional study

PURPOSE
While testosterone therapy can improve the various pathologies associated with adult-onset testosterone deficiency (TD), Summary of Product Characteristics (SPC) of five testosterone preparations caution that treatment may be associated with hypertension. This paper evaluates the impact of testosterone undecanoate (TU) on blood pressure (BP) in men with adult-onset TD.


MATERIALS AND METHODS
Of 737 men with adult-onset TD in an on-going, observational, prospective, cumulative registry, we studied changes in BP using non-parametric sign-rank tests at final assessment and fixed time points. We used multiple regression analysis to establish factors (baseline BP, age, change/baseline waist circumference [WC] and hematocrit [HCT] and follow-up) potentially associated with BP change in men on TU.


RESULTS
TU was associated with significant reductions in systolic, diastolic BP and pulse pressure, regardless of antihypertensive therapy (at baseline or during follow-up), larger reductions were seen with concurrent antihypertensive therapy. In men never on antihypertensive agents, median changes (interquartile range [IQR]) in systolic BP, diastolic BP and pulse pressure were -12.5 (-19.0, -8.0), -8.0 (-14.0, -3.0), and -6.0 (-10.0, -1.0) mmHg, respectively at final assessment, with only baseline BP values inversely associated with these changes (HCT and WC were not significantly associated). In men not on TU, systolic BP, diastolic BP, and pulse pressure significantly increased. In the TU treated men only 1 of the 152 men (not on antihypertensive agents at baseline) were started on antihypertensives during follow-up. In contrast 33 of the 202 men on antihypertensives (at baseline or follow-up) had the antihypertensive agent discontinued by the end of the follow-up.


CONCLUSIONS
TU was associated with lowering of BP during follow-up irrespective of antihypertensive therapy, with greater reductions in men with higher baseline BP. In the context of SPC warnings, our long-term data provide reassurance on the effect of TU on BP.

Testosterone Replacement Therapy: Effects on Blood Pressure in Hypogonadal Men.

Adult-onset testosterone deficiency (TD) in men is diagnosed by the finding of low serum testosterone levels and recognised, associated symptoms. The condition has high prevalence in men over 50 years of age, particularly those with type 2 diabetes (T2DM). Accumulating data show adult-onset TD is associated with increased mortality risk. We review the literature and consider the evidence suggesting testosterone therapy (TTh) reduces mortality, especially in men with T2DM. We previously reported that in the Burntwood Lichfield Atherstone Sutton Coldfield Tamworth (BLAST) study screened cohort of men with adult-onset TD and T2DM adult-onset TD was associated with increased mortality with TTh decreasing this higher mortality. The data hinted that the effect was greater in older men. We confirmed this observation with statistical analyses to study the effect of age on the association between adult-onset TD and mortality; Cox regression analysis demonstrated that the reduced risk (hazard ratio: 0.61, 95% CI: 0.38–0.96) following TTh was restricted to men above the median age of 65.89 years. Finally, we speculate on putative mechanisms that may mediate these associations. Heterogeneity in men with adult-onset TD is expected in view of its definition of low testosterone levels together with associated clinical phenotypes that are not always directly related. Many of these classifying phenotypes are associated with increased mortality. Thus, it is perhaps possible that mechanism(s) of all-cause mortality reduction following TTh is via the impact on these associated phenotypes such as the metabolic syndrome (MetS), hyperglycaemia, hypertension, dyslipidaemia, low haematocrit, sex hormone binding levels, erectile dysfunction, etc. We propose that further research studying the effect of TTh takes heterogeneity into account. 

Adult-onset testosterone deficiency: the usefulness of hormone replacement in reducing mortality in men with this common age-related condition

Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging. A multi-disciplinary panel from BSSM reviewed the available literature on TD and provide evidence-based statements for clinical practice. Evidence was derived from Medline, EMBASE and Cochrane searches on hypogonadism, testosterone therapy (T Therapy) and cardiovascular safety from May 2017 to September 2022. This revealed 1,714 articles, including 52 clinical trials and 32 placebo-controlled randomised controlled trials. A total of twenty-five statements are provided, relating to five key areas: screening, diagnosis, initiating T Therapy, benefits and risks of T Therapy, and follow-up. Seven statements are supported by level 1 evidence, eight by level 2, five by level 3, and five by level 4. Recent studies have demonstrated that low levels of testosterone in men are associated with increased risk of incident type 2 diabetes mellitus, worse outcomes in chronic kidney disease and COVID 19 infection with increased all-cause mortality, along with significant quality of life implications. These guidelines should help practitioners to effectively diagnose and manage primary and age-related TD.

The British Society for Sexual Medicine Guidelines on Male Adult Testosterone Deficiency, with Statements for Practice

British Society for Sexual Medicine (BSSM) Position statement on Premature Ejaculation.

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The British Society for Sexual Medicine Guidelines on Male Adult Testosterone Deficiency, with Statements for Practice

British Society for Sexual Medicine (BSSM) Position statement on Premature Ejaculation.