Secondary erythrocytosis refers to an elevation in hemoglobin or hematocrit due to elevated serum erythropoietin levels. Medications including testosterone and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are increasingly recognized as causes of secondary erythrocytosis. We conducted a systematic review to inform the clinical management of drug-induced erythrocytosis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search in MEDLINE, EMBASE, CENTRAL (all via Ovid), and Google Scholar. Of the 2036 articles screened for eligibility, 45 studies were included in our review, with 35 studies on testosterone and other androgen use, 5 studies on SGLT-2 inhibitors, 3 studies on antiangiogenic tyrosine kinase inhibitors (TKIs), 1 study on erythropoiesis-stimulating agents, and 1 study on a treatment regimen for multidrug-resistant tuberculosis. Cisgender and transgender men on prescription testosterone had erythrocytosis rates of up to 66.7%, with intramuscular formulations, higher doses, and older age associated with increased risk of erythrocytosis. Up to 2.7% of men on testosterone therapy developed thromboembolic events. Among individuals on SGLT-2 inhibitors, erythrocytosis rates ranged from 2.1% to 22%, with those who discontinued therapy demonstrating improvement or resolution of erythrocytosis. Thromboembolic events were reported in up to 10% of these individuals. Antiangiogenic TKIs were studied in patients with cancer, with erythrocytosis developing in up to 43.5% of patients. Drug-induced erythrocytosis is a heterogeneous condition for which there is no clear consensus among clinicians about its diagnosis and management. We offer recommendations for clinical practice within the scope of this systematic review, although further research is required.

Aging is associated with a reduction in skeletal muscle fiber size and number, leading to a decline in physical function and structural integrity-a condition known as sarcopenia. This syndrome is further characterized by elevated levels of inflammatory mediators that promote skeletal muscle catabolism and reduce anabolic signaling.Androgens are involved in various biological processes, including the maintenance, homeostasis and trophism of skeletal muscle mass. The decline in androgen levels contributes, indeed, to androgen deficiency in aging people. Such clinical syndrome exacerbates the muscle loss and fosters sarcopenia progression. Nevertheless, the mechanism(s) by which the reduction in androgen levels influences sarcopenia risk and progression remains debated and the therapeutic benefits of androgen-based interventions are still unclear. Given the significant societal and economic impacts of sarcopenia, investigating the androgen/androgen receptor axis in skeletal muscle function is essential to enhance treatment efficacy and reduce healthcare costs.This review summarizes current knowledge on the role of male hormones and their-dependent signaling pathways in sarcopenia. We also highlight the cellular and molecular features of this condition and discuss the mechanisms by which androgens preserve the muscle homeostasis. The pros and cons of clinical strategies and emerging therapies aimed at mitigating muscle degeneration and aging-related decline are also presented.

Performance-enhancing drugs, such as testosterone, are used by athletes and youth to increase muscle growth and strength, particularly among males. However, these therapies potentially pose health risks, including liver toxicity, gynecomastia, and hair loss. Testosterone use is rising for performance enhancement, physical appearance, and resistance training, but there remains an absence of standardized guidelines for safe dosages. This study examines the relationship between testosterone use and hair health in males, aiming to develop guidelines for safe, responsible testosterone use. Understanding treatment outcomes in this context is crucial for informed healthcare.

Reproductive effort incurs the cost of biological aging and morbidity by compromising somatic maintenance when key resources are limited. Oxidative stress is positively correlated with reproductive effort in adult human females and non-human male animal models, but human males are understudied. We hypothesized that due to its anabolic and metabolic promotion of reproductive effort in human males, testosterone would be positively associated with biomarkers of oxidative stress.

Urinary testosterone in adult Shuar males of Amazonia Ecuador, a foraging/horticultural population, was measured with urinary 8-hydroxy-2' -deoxyguanosine (8-OHdG), a biomarker of oxidative stress, and Cu/Zn superoxide dismutase (Cu/Zn SOD), a protective antioxidant against oxidative stress. Age and anthropometric measures were included in multivariate models.

No significant correlation was observed between testosterone and 8-OHdG, r2 = 0.01, p = 0.61, n = 29, or Cu/Zn SOD, r2 = 0.0005, p = 0.93, n = 17. Multiple linear regression models including testosterone, Cu/Zn SOD, anthropometrics, and age, with 8-OHdG as the dependent variable, were modestly supportive of an association. The most parsimonious 8-OHdG model included age, Cu/Zn SOD, and testosterone (R2 adjusted = 0.38, p = 0.04, AICc = 141.95). All multivariate models for Cu/Zn SOD were not significant (p > 0.05).

Oxidative stress may not be a cost of reproductive effort in this population of adult males; perhaps due to consistently low testosterone levels in non-industrialized populations, differences in the metabolic cost of reproductive effort between males and females (i.e., aerobic metabolism), and/or study limitations based on cross-sectional measures of oxidative stress and testosterone.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by a genetic mutation in the Dmd gene. Dystrophin mutant mice (mdx) have traditionally been used for DMD research as a disease model in the preclinical stage; however, mdx mice exhibit only very mild phenotypes to partially mimic muscle degeneration and regeneration. To overcome this limitation in preclinical studies, DMD mutant rats (DMD rats) generated by CRISPR/Cas were used as a DMD model to exhibit age-dependent progressive muscle degeneration and pathophysiological features similar to DMD patients and more severe than those displayed by mdx mice. TEI-SARM2 is a non-steroidal, orally available selective androgen receptor modulator (SARM) developed as a pharmaceutical candidate for the treatment of muscle wasting diseases based on its potent anabolic activity on skeletal muscle mass. In this study, long-term treatment of daily oral administration of TEI-SARM2 to DMD rats significantly improved muscle function (endurance and strength) assessed by grip and tetanic force measurements. TEI-SARM2 did not increase the muscle weight of hindlimbs in male DMD rats; moreover, long-term, weekly oral administration for 24 weeks improved muscle function with reduced side effects on the prostate and testes weight. Histological analysis showed that TEI-SARM2 significantly reduced adipose tissue infiltration in DMD muscle. In female DMD rats, both daily and weekly TEI-SARM2 treatment showed anabolic effects and enhanced muscle strength and endurance. Taken together, these results indicate that TEI-SARM2 has non-anabolic and anabolic effects that improve dystrophic muscle dysfunction and can be a supportive therapeutic option for DMD.

This study investigated whether home-based bathing intervention (HBBI) improve muscle strength gain and protect cardiovascular function by short-term resistance training (RT). Thirty-one healthy young men measured the maximum voluntary isometric contraction (MVC) of knee extensor, electrically evoked knee extension torque, and mean arterial pressure (MAP). Then, participants were divided into three groups with matching MVC: shower without bathing (control, n = 10), thermoneutral bathing (36°C-bathing, n = 10), and hot bathing (40°C-bathing, n = 11), and conducted 2 weeks of HBBI. Following familiarization for HBBI, participants completed 2 weeks of HBBI and acute RT (five sessions of three sets of 10 isometric knee extension at 60% MVC). Baseline neuromuscular and cardiovascular function was assessed again following completion of the 2 weeks of intervention. MVC was non-significantly increased after the RT period in 40°C-bathing with large effect size (partial η2 = 0.450). The electrically evoked knee extension torque (10/100-Hz ratio) was significantly increased after the RT period in control (p = 0.020). MAP did not alter due to bathing intervention and RT (all p > 0.05). HBBI improved muscle strength without RT-induced alteration of peripheral muscle condition. Shower without bathing reduced muscle strength gain but increased peripheral muscle condition. Short-term RT does not adversely affect the cardiovascular function, regardless of HBBI.

This study examined the effect of resistance training (RT) by itself and in combination with supraphysiological administration of nandrolone decanoate (ND) on the inflammatory, apoptotic, and oxidative stress response in cardiac tissue. The effect of the training and androgen intervention on adiponectin expression, a potential cardio protectant was also examined.

Forty male C57Bl/6J mice, 3 months of age were randomized into four groups (n = 10 per group). Two groups of animals performed a 3-day per week RT program for 7-weeks, while the other two groups remained sedentary (SED). The RT and SED animals were further randomized into an androgen group (RTA and SEDA, respectively) or a sham group (RTS and SEDS, respectively). Animals in the RTA and SEDA groups received 38-mg·kg-1 injected once per week. Mice from RTS and SEDS received sham injections.

Main effects for group indicated that RT resulted in significant elevations in NFκβ (p < 0.001), glutamine peroxidase (GPX) (p = 0.007) and adiponectin (p < 0.001). Main effects for treatment indicated that ND administration resulted in greater elevations in NFκβ (p = 0.01) and TNF-α (p = 0.017). In addition, TNF-α expression was greater in RTA compared to RETS (p = 0.006) and the adiponectin response in RTA was greater (p's < 0.05) than all other groups. A significant correlation was noted between average training volume during the RT program and GPX expression (r = 0.716, p < 0.001).

Results indicate that RT and ND administration can increase markers of apoptosis and inflammation. Elevations in adiponectin expression suggest that it may act as a compensatory mechanism supporting cardiovascular health.

Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.

Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity. Testosterone is known to cause muscle hypertrophy, reduced fat mass, and increased body strength. The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia. We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young, treated non-diabetic young, untreated diabetic young, and treated diabetic young rats, and 32 aged Wistar rats to groups of untreated non-diabetic elderly, treated non-diabetic elderly, untreated diabetic elderly, and treated diabetic elderly rats, with eight animals each group. The treated non-diabetic and treated diabetic groups received injections of 15 ​mg/kg weight Durateston™. All the trained groups performed aquatic training with an overload of 5% of the body mass. Following the experiment, we anesthetized and euthanized the animals after exercise (exhaustion). Hemoglobin, erythrocytes, and hematocrit values were higher in the treated groups. The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups (p ​< ​0.05). As for the lipid profile, untreated rats had the highest values. Glucose concentration was higher at rest and after exercise in the untreated diabetic groups (p ​< ​0.05). Lactate was more elevated in the untreated diabetic groups, and the testosterone-treated groups performed the longest swimming time after the maximal test (p ​< ​0.05). The use of testosterone in conjunction with physical exercise improved physical performance in water, blood glucose, and lipid profiles.

Sex differences in sports performances continue to attract considerable scientific and public attention, driven in part by high profile cases of: 1) biological male (XY) athletes who seek to compete in the female category after gender transition, and 2) XY athletes with medical syndromes collectively known as disorders or differences of sex development (DSDs). In this perspective, we highlight scientific evidence that informs eligibility criteria and applicable regulations for sex categories in sports. There are profound sex differences in human performance in athletic events determined by strength, speed, power, endurance, and body size such that males outperform females. These sex differences in athletic performance exist before puberty and increase dramatically as puberty progresses. The profound sex differences in sports performance are primarily attributable to the direct and indirect effects of sex-steroid hormones and provide a compelling framework to consider for policy decisions to safeguard fairness and inclusion in sports.

To assess the effect of perioperative testosterone supplementation on orthopaedic surgical outcomes.

Three online databases were searched from database inception until September 2024. Three reviewers independently screened all titles, abstracts, and full texts of articles investigating perioperative testosterone use in orthopaedic surgery. English-language studies, human studies, Level I or II randomized controlled trials, and studies examining testosterone supplementation given during the perioperative period of an orthopaedic surgery were included. Demographic data, surgical indications, details of testosterone use, and outcomes were recorded and analyzed.

In total, 1,895 records were screened and 5 randomized controlled trials (4 Level I, 1 Level II) were included. One study evaluated patients undergoing elective total knee arthroplasty. One study investigated patients undergoing elective anterior cruciate ligament reconstruction. Three studies evaluated the effects of testosterone on patients undergoing hip fracture fixation. In total, 189 patients were included, with 84 receiving perioperative testosterone and 105 receiving placebo or a control intervention. One study showed length of stay was lower and ability to stand significantly improved in the testosterone group; 1 study revealed significant improvement in body composition and bone mineral density (BMD); 1 study showed testosterone and protein supplementation improved lean body mass, functional scores, and health-related quality-of-life scores; 1 study revealed perioperative testosterone supplementation increased lean mass postoperatively; and 1 short-term and underpowered study did not show significant improvement in the measured outcomes. The 5 studies showed heterogeneity in patient populations, procedure type, dosage, duration, testosterone therapy protocol, clinical outcomes, and follow-up duration.

Although evidence regarding orthopaedic perioperative use of testosterone replacement therapy is heterogeneous, 4 randomized controlled trials reviewed here found that testosterone supplementation improved clinical outcomes, body composition, and BMD. All 4 studies showed significant improvements in functional independence, BMD, muscle volume in the operative and nonoperative leg, Harris hip score, gait speed, Katz score, lean body mass, and strength.

Level II, systematic review of Level I and II studies.

Hypogonadism in men is associated with an adverse metabolic phenotype and increased mortality. Reciprocally, obesity and insulin resistance can suppress the hypothalamic-pituitary-gonadal axis in the absence of structural organic disease, further perpetuating a cycle of metabolic dysfunction and low testosterone. The mechanisms underpinning this bidirectional association are complex as hypogonadism is a heterogenous syndrome, and obesity is associated with metabolic perturbations in glucose and lipid metabolism even in the presence of normal testicular function. However, distinct molecular defects specific to testosterone deficiency have been identified in pathways relating to glucose and lipid metabolism in target metabolic depots such as adipose tissue and skeletal muscle. This review discusses the etiology and prevalence of metabolic disease in male hypogonadism, with a specific focus on both disease mechanisms and novel potential approaches to enhance our understanding.

Physical activity highly impacts the neuroendocrine system and hormonal secretion. Numerous variables, both those related to the individual, including genetics, age, sex, biological rhythms, nutritional status, level of training, intake of drugs or supplements, and previous or current pathologies, and those related to the physical activity in terms of type, intensity, and duration of exercise, or environmental conditions can shape the hormonal response to physical exercise. The aim of this review is to provide an overview of the effects of physical exercise on hormonal levels in the human body, focusing on changes in concentrations of hormones such as cortisol, testosterone, and insulin in response to different types and intensities of physical activity. Regular monitoring of hormonal responses in athletes could be a potential tool to design individual training programs and prevent overtraining syndrome.

The purpose of this study is to identify social perceptions and public concerns related to male hormone levels and prostate cancer. To do so, we analyzed news and community data from Naver, Daum, and Google, the three most active social media platforms in South Korea, to explore how male hormone levels and benign prostatic hyperplasia (BPH) are covered in the media and discussed within online communities.

We analyzed three years of data from community discussions and news articles from July 2021 to June 2024. Text mining techniques were used to collect data with the keyword 'male hormone levels' to understand the portrayal of these issues in news and online communities as well as the public's social perceptions and concerns.

The analysis showed that news coverage of 'male hormone levels' initially drew public attention by highlighting information related to celebrities and events while discussion on 'prostate enlargement' largely focused on medical treatments and information. The online community served as a platform where news-triggered issues were rediscussed through personal experiences and opinions, thus influencing public perceptions. However, the community discussions leaned more towards sexual dysfunction rather than prostate enlargement. These findings suggest that while news and online communities shape public awareness in different way, they both contribute to shaping social understanding of male hormone level and BPH.

This study highlights the significant roles that news and online communities play in shaping social perceptions of male hormone levels and BPH. However, sensationalism in media coverage may lead to biased information and reinforce false stereotypes. Future studies can be done to incorporate data from diverse cultural contexts and extend the data collection period to further explore shifts in public perceptions and the evolution of social discussions surrounding male hormone levels and BPH.

In the United States, testosterone therapy has markedly increased in recent years. Currently, there is a paucity of evidence evaluating the risk of ligamentous injuries in patients taking testosterone replacement therapy (TRT).

The purpose of this study was to quantify the association between TRT and the incidence of anterior cruciate ligament (ACL) injuries and the subsequent risk of ACL reconstruction (ACLR) failure. It was hypothesized that individuals receiving TRT would demonstrate an increased risk for index ACL injury and ACL rerupture.

Cohort study; Level of evidence, 3.

This is a retrospective cohort study utilizing the PearlDiver database. Records were queried between 2011 and 2020 for patients aged 18 to 59 years who filled a testosterone prescription. A matched control group based on age, sex, Charlson Comorbidity Index, tobacco use, diabetes, and hypothyroidism consisted of patients aged 18 to 59 years who had never filled a prescription for exogenous testosterone. International Classification of Diseases, 9th and 10th Revisions and Current Procedural Terminology (CPT) codes were utilized to identify patients with ACL injuries and those undergoing reconstruction. Multivariable logistic regression was used to compare rates of ACL injury at 6 months, 1 year, and 2 years after initiating TRT. ACLR failure was also examined at 1-year intervals for 5 years for individuals filling a TRT prescription.

A total of 851,816 patients were enrolled, with 425,908 patients in the TRT and control groups, respectively. The TRT cohort was significantly more likely to experience an ACL tear during 6-month (OR, 2.66; 95% CI, 2.17-3.26), 1-year (OR, 2.46; 95% CI, 2.11-2.86), and 2-year (OR, 2.22; 95% CI, 1.98-2.48) periods. The rate of reconstruction failure did not differ between the 2 cohorts at up to 5 years of follow-up (P > .05).

Patients receiving TRT were significantly more likely to sustain a primary ACL rupture but were not at a statistically significant increased risk of reconstruction failure.

Testosterone plays important roles in reproductive behaviour in many species. Despite a common belief that testosterone regulates fluctuations in human sexual desire, there is little direct evidence that relates within-person changes in natural testosterone production to within-person changes in sexual desire. Here, we measured daily salivary testosterone concentrations from 41 adult men for one month, along with daily self-reports of sexual desire (n = 759 observations for the main analyses). We analysed concurrent relationships between within-person changes in testosterone and desire, and also lagged relationships that were analysed using a continuous-time modelling framework. We found no evidence for significant, positive relationships between testosterone and desire, which argues against the notion that day-to-day changes in eugonadal men's baseline testosterone regulates changes in their sexual desire. However, additional analyses provided preliminary evidence for a positive relationship between testosterone and self-reported courtship effort, particularly on days when single participants interacted with potential romantic partners. Our findings add original evidence regarding day-to-day associations between testosterone and desire, and suggest that testosterone above minimum threshold concentrations does not increase sexual desire. We propose that the evolved functions of testosterone in human males are more closely associated with courtship efforts than with sexual desire.

This study aimed to investigate the effects of testosterone replacement therapy on hemostasis and some procoagulant gene expression in mice. 42 mice were randomly divided into two groups of non-orchiectomized (non-ORX) and orchiectomized (ORX) with three subgroups (n = 7) each, were subcutaneously administered with sesame oil (control), 2 and 20 mg/kg/week testosterone enanthate. Orchiectomized mice were allowed to recover for one week before treatment. On the 7th week of treatment, blood samples were collected for coagulation parameters analysis and measurement of plasma testosterone levels. Moreover, quantitative real-time PCR analysis was performed on liver samples to assess the expression of factor IX, factor X, and prothrombin genes. The results showed that supraphysiological doses (20 mg/kg) of testosterone significantly increased plasma testosterone levels in all groups, while physiological doses (2 mg/kg) only increased testosterone levels in non-ORX animals. Although testosterone administration had no effect on prothrombin time (PT) and activated partial thromboplastin time (aPTT), supraphysiological doses reduced bleeding time and clotting time. Furthermore, platelet count increased in a dose-dependent manner with testosterone enanthate treatment. The expression of coagulation factors was also decreased with supraphysiological doses of testosterone. In conclusion, testosterone had significant effects on primary hemostasis and common coagulation pathway, including increased platelet number and aggregation, decreased clotting time, and altered gene expression of coagulation factors.

Testosterone, the major androgen, influences the reproductive and non-reproductive systems in males and females via binding to the androgen receptor (AR). Both circulating endogenous testosterone and muscle AR protein content are positively associated with muscle mass and strength in males, but there is no such evidence in females. Here, we tested whether circulating testosterone levels were associated with muscle mass, function, or the muscle anabolic response to resistance training in pre-menopausal females. Twenty-seven pre-menopausal, untrained females (aged 23.5 ± 4.8 years) underwent a 12-week resistance training programme. Muscle strength, size, power, and plasma and urine androgen hormone levels were measured. Skeletal muscle biopsies were collected before and after the training programme to quantify the effect of resistance training on AR content and nuclear localisation. Primary muscle cell lines were cultured from a subset (n = 6) of the participants' biopsies and treated with testosterone to investigate its effect on myotube diameter, markers of muscle protein synthesis and AR cellular localisation. Physiological levels of total testosterone were not associated with muscle mass or strength at baseline or with the changes in muscle mass and strength that occurred in response to resistance training in our cohort of pre-menopausal females. In contrast, bioavailable testosterone and the proportion of nuclear-localised AR were positively associated with skeletal muscle mass and strength in pre-menopausal females. In vitro, supra-physiological doses of testosterone increased myocyte diameter, but this did not occur via the Akt/mTOR pathway as previously suggested. Instead, we show a marked increase in AR nuclear localisation with testosterone administration in vitro. KEY POINTS: Total circulating testosterone was not related to muscle mass or strength before or after resistance training in pre-menopausal females. Bioavailable testosterone was positively related to exercise-induced muscle hypertrophy in pre-menopausal females. In vivo nuclear localisation of the androgen receptor was positively related to muscle mass in pre-menopausal females at baseline, but not to resistance training-induced hypertrophy. Testosterone treatment induced androgen receptor nuclear translocation but did not induce mTOR signalling in primary skeletal myocytes cultured from pre-menopausal female muscle.

Polyfluoroalkyl substances (PFAS) are known endocrine disruptors, that have been the subject of limited research regarding their impact on human lean body mass. The aim of this study was to investigate the effects of PFAS exposure on lean body mass.

We performed a cross-sectional data analysis involving 1022 adolescents and 3274 adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2018, whose lean body mass was measured by dual-energy X-ray absorptiometry. The lean mass index (LMI) was calculated as lean body mass dividing by the square of height. The association between PFAS and LMI was examined through a multivariate-adjusted weighted generalized linear model. Moreover, weighted quantile sum (WQS) regression models were employed to futher examine the relationship between the mixture of PFAS and LMI.

Regression analyses revealed an inverse correlation between PFAS exposure and LMI after adjusting for potential covariates. Adults with higher serum PFAS concentrations manifested a reduction in whole LMI ( β  = -0.193, 95 % confidence interval (CI): -0.325 to -0.06). Notably, this correlation was particularly significant in adult females and individuals with obesity, and it was observed across diverse anatomical regions, including lower limbs, right arm, trunk, and whole lean body mass. In adult females, the association between PFAS and whole LMI was statistically significant ( β  = -0.294, 95 % CI: -0.495 to -0.094), and a similar trend was found in obese individuals ( β  = -0.512, 95 % CI: -0.762 to -0.261). WQS regression analyses supported the results obtained from weighted linear regression analyses.

Our study suggests that exposure to PFAS, whether individually or in combination, is associated with decreased lean body mass in specific body areas, with sex and obesity serving as major influencing factors.

The digit ratio (2D:4D), the ratio of the lengths of second (2D) to the fourth (4D) fingers, is a proxy indicator of prenatal androgen exposure. On average, males display lower 2D:4D than females. Previous studies have shown that lower 2D:4D ratios were associated with better sports and physical abilities.

To assess whether a challenge condition, imposed by intense exercise, could increase handgrip strength (HGS) associated with 2D:4D.

This cross-sectional experimental study included 90 healthy young Polish adults (40 males, 50 females). They underwent intense physical exercise, before (7 days) and after which they were measured for HGS and 2D:4D. Height and weight were also measured. Analyses of Covariance were employed to delineate associations.

2D:4D had significant predictive effects on the differences in HGS (DHGS) measured in two occasions, without and after, physical exercises. The lower was the 2D:4D, the higher the DHGS, particularly, for the left hand.

The results reconfirmed that the link between prenatal testosterone exposure (indicated by 2D:4D) and physical strength depends on the context, such as a challenged condition.

Uncertainty exists if post-resistance exercise hydrotherapy attenuates chronic inflammatory and hormone responses. The effects of repeated post-resistance exercise water immersion on inflammatory and hormone responses in athletes were investigated.

Male, academy Super Rugby players (n = 18, 19.9 ± 1.5 y, 1.85 ± 0.06 m, 98.3 ± 10.7 kg) participated in a 12-week programme divided into 3 × 4-week blocks of post-resistance exercise water immersion (either, no immersion control [CON]; cold [CWI]; or hot [HWI] water immersion), utilising a randomised cross-over pre-post design. Fasted, morning blood measures were collected prior to commencement of first intervention block, and every fourth week thereafter. Linear mixed-effects models were used to analyse main (treatment, time) and interaction effects.

Repeated CWI (p = 0.025, g = 0.05) and HWI (p < 0.001, g = 0.62) reduced creatine kinase (CK), compared to CON. HWI decreased (p = 0.013, g = 0.59) interleukin (IL)-1ra, compared to CON. HWI increased (p < 0.001-0.026, g = 0.06-0.17) growth factors (PDGF-BB, IGF-1), compared to CON and CWI. CWI increased (p = 0.004, g = 0.46) heat shock protein-72 (HSP-72), compared to HWI.

Post-resistance exercise CWI or HWI resulted in trivial and moderate reductions in CK, respectively, which may be partly due to hydrostatic effects of water immersion. Post-resistance exercise HWI moderately decreased IL-1ra, which may be associated with post-resistance exercise skeletal muscle inflammation influencing chronic resistance exercise adaptive responses. Following post-resistance exercise water immersion, CWI increased HSP-72 suggesting a thermoregulatory response indicating improved adaptive inflammatory responses to temperature changes, while HWI increased growth factors (PDGF-BB, IGF-1) indicating different systematic signalling pathway activation. Our data supports the continued use of post-resistance exercise water immersion recovery strategies of any temperature during in-season competition phases for improved inflammatory adaptive responses in athletes.

Sex as a biological variable is an underappreciated aspect of biomedical research, with its importance emerging in more recent years. This review assesses the current understanding of sex differences in human physical performance. Males outperform females in many physical capacities because they are faster, stronger and more powerful, particularly after male puberty. This review highlights key sex differences in physiological and anatomical systems (generally conferred via sex steroids and puberty) that contribute to these sex differences in human physical performance. Specifically, we address the effects of the primary sex steroids that affect human physical development, discuss insight gained from an observational study of 'real-world data' and elite athletes, and highlight the key physiological mechanisms that contribute to sex differences in several aspects of physical performance. Physiological mechanisms discussed include those for the varying magnitude of the sex differences in performance involving: (1) absolute muscular strength and power; (2) fatigability of limb muscles as a measure of relative performance; and (3) maximal aerobic power and endurance. The profound sex-based differences in human performance involving strength, power, speed and endurance, and that are largely attributable to the direct and indirect effects of sex-steroid hormones, sex chromosomes and epigenetics, provide a scientific rationale and framework for policy decisions on sex-based categories in sports during puberty and adulthood. Finally, we highlight the sex bias and problem in human performance research of insufficient studies and information on females across many areas of biology and physiology, creating knowledge gaps and opportunities for high-impact studies.

Female gender is one of the commonly mentioned risk factors for anterior knee pain (AKP), among a spectrum of other factors including anatomical, biomechanical, hormonal, behavioral and psychological elements contributing to its development. Despite the focus on individual risk factors, there's a notable gap in comprehending how gender influences and interacts with other risk factors. The objective of this review was to identify and emphasize the connections between these interactions, gender-related risk factors for AKP, and the potential mechanisms that explain their associations with other risk factors, aiming to aid in the creation of precise prevention and treatment approaches. Gender influences the majority of risk factors for AKP, including anatomical, biomechanical, hormonal, behavioral and psychological factors. Women have on average smaller patellae, higher patellofemoral cartilage stress and for AKP, disadvantageous trochlear morphology, ligament and muscle composition and unfavorable neuromuscular control pattern. In contrast, men show on average an increased ability to strengthen their hip external rotators, which are both protective against AKP. Particularly in kinetic and kinematic analysis, men have been shown to have a distinctly different risk factor profile than women. Sex hormones may also play a role in the risk of AKP, with estrogen potentially influencing ligamentous laxity, increasing midfoot loading and affecting neuromuscular control of the lower extremities and testosterone positively affecting muscle mass and strength. The higher incidence of AKP in women is likely due to a combination of slightly increased risk factors. Although all risk factors can be present in both men and women and the holistic evaluation of each individual's risk factor composition is imperative regardless of gender, knowing distinctive risk factors may help with focused evaluation, treatment and implementing preventive measures of AKP.

Androgens, formerly known as anabolic-androgenic steroids, mimic the effects of testosterone and are being increasingly abused for nonmedical purposes such as body and performance enhancement. Androgen abuse is associated with increased mortality, and multisystem adverse effects have been reported, including cardiovascular toxicity, infertility, hypogonadism, hepatotoxicity, and mental health disorders. Men may present with the negative health consequences of androgen abuse even despite cessation for a number of years. There is frequently a reluctance to disclose androgen abuse, and substances are often sourced from the black market, which is not regulated and where the products sold may be counterfeit. All men should be encouraged to stop androgen abuse. Managing associated adverse effects will be organ-specific and is complex due to physical and neuropsychiatric symptoms, substance dependence, and high rates of relapse. Given the broad reach and prolonged adverse effects of androgen abuse, clinicians across medical specialties should have an awareness of androgen abuse, its increasing prevalence, and the harms it poses to men and their families. This narrative review aims to summarize the adverse effects and risks associated with androgen abuse.

Anaemia is a common but treatable condition that predicts adverse clinical outcomes. However, standards of anaemia management vary considerably.

To estimate the prevalence of anaemia and extent of screening for common underlying causes in the healthcare system in the Republic of Ireland.

We conducted a retrospective cohort study of 112 181 adult patients, aged ≥18 years, who had a full blood count performed in 2013, using data from the National Kidney Disease Surveillance System.

The prevalence of anaemia was determined across demographic and clinical subgroups, according to World Health Organization (WHO) definitions. The proportion screened for iron, vitamin B12, and folate deficiency was determined within a 3-month follow-up period and the corresponding prevalence for each deficiency determined.

The overall prevalence of anaemia was 12.0% (95% confidence interval [CI] = 11.8% to 12.2%) and was higher in women than men (13.2% versus 10.5%, P<0.001). Anaemia increased with advancing age (33.4% for those aged >75 years) and worsening kidney function (8.2%, 10.9%, 33.2%, and 63.8% for each estimated glomerular filtration rate [eGFR] categories >90, 60-89, 30-59 and <30 ml/min/1.73 m², respectively, P<0.001). After 3-months' follow-up, the proportion screened for iron deficiency was 11.2% based on transferrin saturation and 33.7% using serum ferritin. Screening for folate and B12 deficiency was 17.6% and 19.8%, respectively. Among screened patients, the prevalence of iron deficiency, B12, and folate deficiency was 37.0%, 6.3%, and 5.8%, respectively.

The burden of anaemia in the healthcare system is substantial especially for older patients and those with advanced kidney disease. Low screening rates for iron, B12, and folate deficiency are common and warrant quality improvement initiatives.

The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism (MOSH) with emerging evidence on the role of testosterone therapy. We aim to provide an updated and practical approach towards its management. We did a comprehensive literature search across MEDLINE (via PubMed), Scopus, and Google Scholar databases using the keywords "MOSH" OR "Obesity-related hypogonadism" OR "Testosterone replacement therapy" OR "Selective estrogen receptor modulator" OR "SERM" OR "Guidelines on male hypogonadism" as well as a manual search of references within the articles. A narrative review based on available evidence, recommendations and their practical implications was done. Although weight loss is the ideal therapeutic strategy for patients with MOSH, achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice. Therefore, androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity. However, there is conflicting evidence for the appropriate use of testosterone replacement therapy (TRT), and it can also be associated with complications. This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH. Before starting testosterone replacement in functional hypogonadism of obesity, it would be desirable to initiate lifestyle modification to ensure weight reduction. TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients. Balancing the risks and benefits of TRT should be considered in every patient before and during long-term management.

Levels of the male sex hormone testosterone are generally stable in the age interval 20-70 years, but several studies indicate an earlier, age-dependent decline. Testosterone deficiency is often underdiagnosed and under-treated, but replacement therapy has nonetheless increased during the last couple of years. Owing to possible negative side effects, alternative treatments have been investigated, including different supplementation protocols. The aim of this study was to investigate the effect of probiotic supplementation on the testosterone level in healthy men aged between 55 and 65. Hence, 12 weeks randomized, double-blinded, placebo-controlled trial was conducted to investigate the effect on testosterone levels following supplementation of the recognized probiotic Limosilactobacillus reuteri ATCC PTA 6475 on testosterone levels, using high-, low- or placebo treatment. Venous blood samples were collected at baseline, 6 and 12 weeks, for analysis of bloodwork, lipid profile, hormones, and electrolytes. Subjects were also asked to complete a questionnaire. The supplementation had no effect on testosterone levels, neither using high- or low dose, nor placebo. However, a significant decrease of triglyceride levels was observed in the high-dose group. No other parameters showed any significant change. The present study does not support the hypothesis that a probiotic supplementation can increase testosterone levels in ageing men.

Cancer cachexia (CC) is a devastating metabolic syndrome characterized by skeletal muscle wasting and body weight loss, posing a significant burden on the health and survival of cancer patients. Despite ongoing efforts, effective treatments for CC are still lacking. Metabolomics, an advanced omics technique, offers a comprehensive analysis of small-molecule metabolites involved in cellular metabolism. In CC research, metabolomics has emerged as a valuable tool for identifying diagnostic biomarkers, unravelling molecular mechanisms and discovering potential therapeutic targets. A comprehensive search strategy was implemented to retrieve relevant articles from primary databases, including Web of Science, Google Scholar, Scopus and PubMed, for CC and metabolomics. Recent advancements in metabolomics have deepened our understanding of CC by uncovering key metabolic signatures and elucidating underlying mechanisms. By targeting crucial metabolic pathways including glucose metabolism, amino acid metabolism, fatty acid metabolism, bile acid metabolism, ketone body metabolism, steroid metabolism and mitochondrial energy metabolism, it becomes possible to restore metabolic balance and alleviate CC symptoms. This review provides a comprehensive summary of metabolomics studies in CC, focusing on the discovery of potential therapeutic targets and the evaluation of modulating specific metabolic pathways for CC treatment. By harnessing the insights derived from metabolomics, novel interventions for CC can be developed, leading to improved patient outcomes and enhanced quality of life.

Based on the largely untested premise that it is a restorative hormone that may reverse the detrimental impacts of aging, prescription of testosterone (T) has increased in recent decades despite no new clinical indications. It is apparent that middle-aged and older men with low-normal serum T levels are considering T supplementation as an anti-aging strategy. At the same time, there is evidence that physical activity (PA) is at historical lows in the Western world. In this review, we compare the impacts of T treatment aimed at achieving physiological T concentrations in middle-aged and older men, alongside the impacts of ecologically relevant forms of exercise training. The independent, and possible combined, effects of T and exercise therapy on physiological outcomes such as aerobic fitness, body composition and muscular strength are addressed.

Our findings suggest that both T treatment and exercise improve lean body mass in healthy older men. If improvement in lean body mass is the primary aim, then T treatment could be considered, and the combination of T and exercise may be more beneficial than either in isolation. In terms of muscle strength in older age, an exercise program is likely to be more beneficial than T treatment (where the dose is aimed at achieving physiological concentrations), and the addition of such T treatment does not provide further benefit beyond that of exercise alone. For aerobic fitness, T at doses aimed at achieving physiological concentrations has relatively modest impacts, particularly in comparison to exercise training, and there is limited evidence as to additive effects. Whilst higher doses of T, particularly by intramuscular injection, may have larger impacts on lean body mass and strength, this must be balanced against potential risks.

Knowing the impacts of T treatment and exercise on variables such as body composition, strength and aerobic fitness extends our understanding of the relative benefits of physiological and pharmacological interventions in aging men. Our review suggests that T has impacts on strength, body composition and aerobic fitness outcomes that are dependent upon dose, route of administration, and formulation. T treatment aimed at achieving physiological T concentrations in middle-aged and older men can improve lean body mass, whilst exercise training enhances lean body mass, aerobic fitness and strength. Men who are physically able to exercise safely should be encouraged to do so, not only in terms of building lean body mass, strength and aerobic fitness, but for the myriad health benefits that exercise training confers.

Understanding the factors that contribute to exercise response variation is the first step in achieving the goal of developing personalized exercise prescriptions. This review discusses the key molecular and other mechanistic factors, both extrinsic and intrinsic, that influence exercise responses and health outcomes. Extrinsic characteristics include the timing and dose of exercise, circadian rhythms, sleep habits, dietary interactions, and medication use, whereas intrinsic factors such as sex, age, hormonal status, race/ethnicity, and genetics are also integral. The molecular transducers of exercise (i.e., genomic/epigenomic, proteomic/post-translational, transcriptomic, metabolic/metabolomic, and lipidomic elements) are considered with respect to variability in physiological and health outcomes. Finally, this review highlights the current challenges that impede our ability to develop effective personalized exercise prescriptions. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) aims to fill significant gaps in the understanding of exercise response variability, yet further investigations are needed to address additional health outcomes across all populations.

Chemotherapy is a major contributor to cachexia, but studies often investigate male animals. Here, we investigated whether sex modifies the effects of chemotherapy on cachexia and BCAA metabolism. Ten-week-old CD2F1 male and female mice were treated with the chemotherapy drug cocktail folfiri (50 mg/kg 5-fluorouracil, 90 mg/kg leucovorin, and 24 mg/kg CPT11) (drug) or vehicle twice a week for 6 weeks. Insulin tolerance tests were conducted and BCAA levels and metabolism were measured in plasma and tissues. Drug treatment reduced body and skeletal muscle weights and anabolic signaling in both sexes, with females showing worsened outcomes (p < 0.05 for all). Drug treatment increased plasma BCAA only in males, but BCAA concentrations in the skeletal muscle of both sexes were decreased; this decrease was more profound in males (p = 0.0097). In addition, muscle expression of the BCAA transporter LAT1 was reduced; this reduction was more severe in females (p = 0.0264). In both sexes, the (inhibitory) phosphorylation of BCKD-E1αser293 was increased along with decreased BCKD activity. In the liver, drug treatment increased BCAA concentrations and LAT1 expression, but BCKD activity was suppressed in both sexes (p < 0.05 for all). Our results demonstrate that altered BCAA metabolism may contribute to chemotherapy-induced cachexia in a sex-dependent manner.

Aim: The aim of the present study was to investigate the expansion and prevalence of anabolic steroid use by examining the divergent effects between health and drug abuse and to create more awareness around the harmful consequences of these drugs when administered at abusive levels. Methods: A focused and concise literature search was conducted, and 101 high-quality articles were included in the review. Results: The findings underscore the adverse health risks of steroid abuse, emphasizing the stark contrast between health and drug abuse. Conclusions: While steroids and other performance-enhancing drugs can yield muscle growth, strength and even fat loss, abusing these substances can lead to adverse health outcomes. Furthermore, within the fitness subculture, particularly in the realm of bodybuilding, steroid abuse fosters an atmosphere of cheating and deception, frequently downplaying or ignoring the negative and sometimes deadly consequences it brings.

This study aimed to dynamically track the priorities and potential research hotspots in the field of heart failure with sarcopenia. Using CiteSpace, we analyzed the literature on heart failure with sarcopenia from the Web of Science database from 1995 to 2022. The analysis encompassed 507 records, revealing an overall upward trend in annual publication volume. Europe and the United States emerged as the primary regions for publishing, particularly driven by contributions from developed countries such as the United States, Germany, and Italy. Productive institutions included the Charite Universitatsmedizin Berlin, University Medical Center Gottingen, the German Center for Cardiovascular Research (DZHK), Universita Cattolica del Sacro Cuore, and the National Institute on Aging (NIA). Noteworthy academic groups have formed around these institutions; von Haehling S, Anker Stefan D, Springer J, and Doehner W frequently collaborated. The core journals that frequently published articles in this area included Circulation, European Heart Journal, and The Journals of Gerontology Series A-Biological Sciences and Medical Sciences. Based on the keyword analysis, we identified three key research areas. First, the diagnosis and definition of sarcopenia emerged as significant themes. Second, researchers have focused on exploring the mechanisms underlying heart failure with sarcopenia, including inflammation, insulin resistance, and oxidative stress. Finally, treatment strategies, such as physical activity and nutritional support, constitute another critical research theme. Furthermore, potential research hotspots within this field include clinical randomized controlled trials, investigations into inflammatory mechanisms, cardiac rehabilitation, studies on physical activity, androgen receptor modulators, and investigations into clinical outcomes such as cognitive impairment.

Vitamin D status has been associated with sex steroid production. The question is whether vitamin D supplementation has an impact on sex steroid production in infertile men with vitamin D insufficiency?

A single-center, double-blinded, randomized clinical trial. Differences in sex steroids and reproductive hormones were predefined secondary outcomes, vitamin D status at baseline was a predefined subgroup and the primary outcome was differences in semen quality.

A total of 307 infertile men were included and randomized 1:1 to active or placebo treatment for 150 days. Men in the active group initially received an oral bolus of 300,000 IU cholecalciferol, followed by daily supplementation with 1400 IU cholecalciferol and 500 mg calcium.

After intervention, no differences were found in serum concentrations of sex steroids, luteinizing hormone, testosterone/luteinizing hormone ratio or SHBG between the vitamin D and placebo group. However, in a predefined subgroup analysis of men with serum 25OHD ≤ 50 nmol/L, men treated with vitamin D had a significantly higher testosterone/luteinizing hormone ratio [4.2 (3.8-4.4) vs. 3.7 (3.4-4.0); p = 0.033] compared with placebo treatment. In men with vitamin D deficiency, the difference between groups was larger but not significant due to few men with serum 25OHD < 25 nmol/L.

Vitamin D + calcium supplementation did not alter sex steroid production in infertile men. However, vitamin D insufficient men treated with vitamin D supplementation had a significantly higher testosterone/LH ratio compared with placebo-treated men, suggesting that optimal Leydig cell function are dependent on adequate vitamin D status.

Fasting is part of many weight management and health-boosting regimens. Fasting causes substantial metabolic adaptations in the liver that include the stimulation of fatty acid oxidation and ketogenesis. The induction of fatty acid oxidation and ketogenesis during fasting is mainly driven by interrelated changes in plasma levels of various hormones and an increase in plasma nonesterified fatty acid (NEFA) levels and is mediated transcriptionally by the peroxisome proliferator-activated receptor (PPAR)α, supported by CREB3L3 (cyclic AMP-responsive element-binding protein 3 like 3). Compared with men, women exhibit higher ketone levels during fasting, likely due to higher NEFA availability, suggesting that the metabolic response to fasting shows sexual dimorphism. Here, we synthesize the current molecular knowledge on the impact of fasting on hepatic fatty acid oxidation and ketogenesis.

Testosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin-bound, or sex hormone binding globulin (SHBG)-bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic-pituitary-gonadal axis, leading to diminished levels of free testosterone and hypogonadism.

We retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre-cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non-cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients.

Low testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long-term safety of testosterone use remains an open question.

Low serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver-related outcomes and complications.

Androgenic actions of gonadal testosterone are thought to be a major mechanism promoting sex differences in body composition across the lifespan. However, this inference is based on studies of androgen receptor (AR) function in late adolescent or emerging adult rodents. Here we assess body composition and AR expression in skeletal muscle of rats at defined ages, comparing wild-type (WT) to transgenic human skeletal actin-driven AR overexpression (HSAAR) rats which overexpress AR in skeletal muscle. Male and female HSAAR and WT Sprague Dawley rats (N = 288) underwent dual-energy x-ray absorptiometry (DXA) scanning and tissue collection at postnatal day (PND) 1, 10, 21, 42, 70, 183, 243, and 365. Expected sex differences in body composition and muscle mass largely onset with puberty (PND-21), with no associated changes to skeletal muscle AR protein. In adulthood, HSAAR increased tibialis anterior (TA) and extensor digitorum longus mass in males, and reduced the expected gain in gonadal fat mass in both sexes. In WT rats, AR protein was reduced in soleus, but not TA, throughout life. Nonetheless, soleus AR protein expression was greater in male rats than female rats at all ages of sexual development, yet only at PND-70 in TA. Overall, despite muscle AR overexpression effects, results are inconsistent with major sex differences in body composition during sexual development being driven by changes in muscle AR, rather suggesting that changes in ligand promote sexual differentiation of body composition during pubertal timing. Nonetheless, increased skeletal muscle AR in adulthood can be sufficient to increase muscle mass in males, and reduce adipose in both sexes.

Despite the high number of synthetic androgenic-anabolic steroids, testosterone is still misused for doping in amateur and professional sports. However, only few studies investigated the dose-response effects of testosterone beyond its physiological concentrations and in over 90 years of research, no saturation dosage has been experimentally described for exogenous testosterone administration.

We want to elucidate the physiological and pathophysiological effects of supra-physiological testosterone application and close this gap in testosterone dose-response data.

Male orchiectomized rats were treated with different testosterone doses ranging from 0.1 to 50 mg/kg body weight for 3 weeks. Several physiological endpoints (e.g., body weight, organ and muscle weight, muscle strength, muscle fiber size) were examined during and after the termination of the treatment with an adjusted Hershberger assay, open-field-test, and (immuno-)histologic.

The wet weights of androgen responsive organs (penis, prostate, seminal vesicle) showed a significant increase in a dose-dependent manner. Histological evaluation of the prostate showed a significant higher percentage of KI67 positive prostate nuclei in the highest dosage group and an increasing hyperplasia with increasing testosterone administered. A significant anabolic effect was only observed in Levator ani wet weight, and to minor degree for the cardiac muscle. Regarding other skeletal muscles (Musculus soleus and Musculus gastrognemicus), no significant testosterone effects were observed. We showed a significant increasing dosage-response effect for testosterone in androgen responsive organs with saturation at the two highest concentration of 10 and 50 mg/kg body weight.

The dose-dependent androgenic effects of testosterone were well observable and the anabolic effects on muscle tissue were visible although to a lesser degree, without the support of aerobic exercise and a protein rich diet. Future studies should investigate a combinatorial effect of testosterone and training. Nevertheless, with the chosen range of applied testosterone, we showed a saturation of testosterone effects in prostate, seminal vesicle, penis, and Levator ani.

It is hypothesized that there is likely a finite ability for muscular adaptation. While it is difficult to distinguish between a true plateau following a long-term training period and short-term stalling in muscle growth, a plateau in muscle growth has been attributed to reaching a genetic potential, with limited discussion on what might physiologically contribute to this muscle growth plateau. The present paper explores potential physiological factors that may drive the decline in muscle growth after prolonged resistance training. Overall, with chronic training, the anabolic signaling pathways may become more refractory to loading. While measures of anabolic markers may have some predictive capabilities regarding muscle growth adaptation, they do not always demonstrate a clear connection. Catabolic processes may also constrain the ability to achieve further muscle growth, which is influenced by energy balance. Although speculative, muscle cells may also possess cell scaling mechanisms that sense and regulate their own size, along with molecular brakes that hinder growth rate over time. When considering muscle growth over the lifespan, there comes a point when the anabolic response is attenuated by aging, regardless of whether or not individuals approach their muscle growth potential. Our goal is that the current review opens avenues for future experimental studies to further elucidate potential mechanisms to explain why muscle growth may plateau.

In 2017, there were almost 2.5 million high school students who experienced a concussion while playing a sport, raising concern for the neurologic problems that they could face. Some of these athletes may seek to gain a competitive advantage in their sport by utilizing substances like steroids. However, steroid use can cause increased aggression and body mass index (BMI), which might lead to heightened risk for concussions. Despite extensive research, we found no previous evidence linking these two factors.

This analysis aims to investigate steroid use trends in high school athletes and to determine whether there is an association between steroid use and concussions in these athletes.

We conducted a cross-sectional analysis of the cumulative Youth Risk Behavior Surveillance System (YRBSS). Respondents were added if they participated in sports and answered the steroid and concussion prompts. Demographic variables were assessed including age, grade, BMI, gender, and race/ethnicity.

We found that 3.7 % (n=2991) of high school athletes reported previous steroid use and that 20.7 % (n=2273) reported having sustained a concussion. There was a statistically significant difference in steroid use by race/ethnicity (p<0.001), with the highest rate of use (7.2 %) among American Indian/Alaska Natives (AI/AN). A significantly higher prevalence of steroid use occurred in athletes who were males (4.7 %) than females (2.5 %) and in athletes with a BMI>95 % (5.2 %) compared with those with a BMI between 85 and 95 % (3.9 %) and <85 % (3.5 %) (χ2=135.1, p<0.001 and χ2=16.3, p<0.001, respectively). Further, our results showed that the prevalence of steroid use among high school athletes decreased from 3.4 % in 1999 to 1.9 % in 2019, with the most drastic drop occurring between 2015 and 2019-declining 1.9 %. Whereas 19.6 % of athletes reported a concussion without steroid use, 54.6 % of steroid-utilizing athletes reported having experienced a concussion-a statistically significant finding (adjusted odds ratio [AOR]=4.3; 95 % CI: 3.2-5.9). Finally, compared with White athletes, we found that AI/AN athletes were significantly more likely to have sustained a concussion (AOR=2.3; 95 % CI=1.2-4.3).

Although our study found decreasing rates of steroid use among high school athletes from 1999 through 2019, our results also show that steroid use is significantly associated with sustaining a concussion. Additionally, the data from YRBSS also demonstrates that AI/AN high school athletes are more likely to utilize steroids and sustain a concussion. Given the long-term consequences of traumatic brain injuries, we recommend that coaches should be aware of potential steroid use among players, and that coaches, athletic trainers, and physicians should all be aware of concussion protocols and remove players from games for evaluation when a concussion is suspected.

The use of anabolic androgenic steroids (AAS) for strength training and muscle building is a widespread practice among athletes and young individuals. Athletes and bodybuilders are using these substances for various purposes, such as enhancing muscle mass, strengthening their bodies, and enhancing their performances. AAS exert a wide range of physiological effects that result in the activation of central signaling, resulting in adverse effects. Moreover, excessive use of AAS which can be categorized as AAS abuse; is linked to biological and psychological pathologies, which can lead to mortality. Complications arising from steroid abuse involve both cellular and physiological complications. Cellular complications arise when activation of signaling proteins like mTOR, Akt, etc. leads to alteration in protein synthesis pathways, cell cycle, oxidative stress, and apoptosis, contributing to damage at the cellular level. Physiological complications are evident with cardiovascular pathologies, including an altered lipid profile, cardiac hypertrophy, hypogonadism after discontinuation of AAS, and modulation of GABA receptors in the brain, all contributed by the androgen receptor signaling. Clinical complications budding from these altered physiological processes lead to clinical effects like testicular dysfunction, acne, gynecomastia, and neuropsychiatric disorders. Despite potential therapeutic benefits, AAS use is prohibited by the World Anti-Doping Agency (WADA) due to concerns over adverse health effects. This review highlights the molecular mechanisms, physiological processes, and clinical complications arising from the excessive use of AAS among athletes.

No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AASs) usage on the myocellular properties of human skeletal muscle in previous AAS users.

We hypothesized that former AAS users would demonstrate smaller myonuclei domains (ie, higher myonuclei density) than matched controls.

A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size.

Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101-206) and 140 (24-260) weeks in current and former AAS users, respectively (P = .482). Geometric mean (95% CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA to cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = .013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users: beta-coefficient (95% CI) -94 (-169; -18), P = .024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = .031) than controls.

Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA to cytoplasm ratio 4 years after AAS cessation suggestive of enhanced retraining capacity.

Biological sex is a primary determinant of athletic performance because of fundamental sex differences in anatomy and physiology dictated by sex chromosomes and sex hormones. Adult men are typically stronger, more powerful, and faster than women of similar age and training status. Thus, for athletic events and sports relying on endurance, muscle strength, speed, and power, males typically outperform females by 10%-30% depending on the requirements of the event. These sex differences in performance emerge with the onset of puberty and coincide with the increase in endogenous sex steroid hormones, in particular testosterone in males, which increases 30-fold by adulthood, but remains low in females. The primary goal of this consensus statement is to provide the latest scientific knowledge and mechanisms for the sex differences in athletic performance. This review highlights the differences in anatomy and physiology between males and females that are primary determinants of the sex differences in athletic performance and in response to exercise training, and the role of sex steroid hormones (particularly testosterone and estradiol). We also identify historical and nonphysiological factors that influence the sex differences in performance. Finally, we identify gaps in the knowledge of sex differences in athletic performance and the underlying mechanisms, providing substantial opportunities for high-impact studies. A major step toward closing the knowledge gap is to include more and equitable numbers of women to that of men in mechanistic studies that determine any of the sex differences in response to an acute bout of exercise, exercise training, and athletic performance.

Aging is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females demonstrate a distinct pattern of muscle aging compared to males, potentially due to menopause, when the production of endogenous sex hormones declines. This systematic review aims to investigate the current knowledge about the role of estrogen in female skeletal muscle aging. A systematic search of MEDLINE Complete, Global Health, Embase, PubMed, SPORTDiscus, and CINHAL was conducted. Studies were considered eligible if they compared a state of estrogen deficiency (e.g. postmenopausal females) or supplementation (e.g. estrogen therapy) to normal estrogen conditions (e.g. premenopausal females or no supplementation). Outcome variables of interest included measures of skeletal muscle mass, function, damage/repair, and energy metabolism. Quality assessment was completed with the relevant Johanna Briggs critical appraisal tool, and data were synthesized in a narrative manner. Thirty-two studies were included in the review. Compared to premenopausal women, postmenopausal women had reduced muscle mass and strength, but the effect of menopause on markers of muscle damage and expression of the genes involved in metabolic signaling pathways remains unclear. Some studies suggest a beneficial effect of estrogen therapy on muscle size and strength, but evidence is largely conflicting and inconclusive, potentially due to large variations in the reporting and status of exposure and outcomes. The findings from this review point toward a potential negative effect of estrogen deficiency on aging skeletal muscle, but further mechanistic evidence is needed to clarify its role.

Aging is a progressive and irreversible pathophysiological process that manifests as the decline in tissue and cellular functions, along with a significant increase in the risk of various aging-related diseases, including metabolic diseases. While advances in modern medicine have significantly promoted human health and extended human lifespan, metabolic diseases such as obesity and type 2 diabetes among the older adults pose a major challenge to global public health as societies age. Therefore, understanding the complex interaction between risk factors and metabolic diseases is crucial for promoting well-being and healthy aging. This review article explores the environmental and behavioral risk factors associated with metabolic diseases and their impact on healthy aging. The environment, including an obesogenic environment and exposure to environmental toxins, is strongly correlated with the rising prevalence of obesity and its comorbidities. Behavioral factors, such as diet, physical activity, smoking, alcohol consumption, and sleep patterns, significantly influence the risk of metabolic diseases throughout aging. Public health interventions targeting modifiable risk factors can effectively promote healthier lifestyles and prevent metabolic diseases. Collaboration between government agencies, healthcare providers and community organizations is essential for implementing these interventions and creating supportive environments that foster healthy aging.