The association between low serum testosterone levels and all-cause mortality in male and female patients with cardiovascular disease (CVD) was investigated. This study extracted data on CVD patients from the National Health and Nutrition Examination Survey (NHANES) database (1999-2000, 2003-2004, 2011-2012, and 2013-2014). The association between low serum testosterone levels (≤ 300 ng/dL) and all-cause mortality in male and female CVD patients was evaluated using univariate and multivariate Cox regression analyses, with hazard ratios (HR) and 95% confidence intervals (CI). A total of 1,177 participants (689 males) with a mean age of 66.01 ± 12.52 years were included in the study. The median follow-up time was 55 (44, 71) months. Low serum testosterone levels occurred in 487 (70.68%) males and 394 (80.74%) females. Additionally, 202 (29.32%) male patients and 94 (19.26%) female patients with CVD were dead. After adjusting for covariates, low serum testosterone levels were associated with an increased risk of all-cause mortality in male CVD patients (HR = 1.48, 95% CI 1.08-2.02, P = 0.013), while the association was not significant in females. Low serum testosterone levels may be associated with an increased risk of all-cause mortality in male CVD patients, but not in female patients.

TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism. Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-to-event analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

Lycium barbarum extracts have been shown to be effective in male reproductive protection and male infertility. However, its role in enhancing testicular function, such as testosterone synthesis, and the potential mechanism remain to be understood. To elucidate the effects of Lycium barbarum glycopeptide (LbGp) on testosterone synthesis, we isolated primary Leydig cells (LCs) from testes and performed RNA sequencing (RNA seq) on LCs treated with LbGp. In this study, we demonstrated that LbGp promoted testosterone synthesis in LCs both in vivo and in vitro. We also demonstrated that LbGp elevated adenosine 5'-triphosphate (ATP) synthesis and cell proliferation by enhancing glucose metabolism. Mechanistically, LbGp upregulated testosterone synthesis by suppressing TGF-β pathway and enhancing the expression of steroidogenic genes: Cyp11a1, Hsd3b1, Hsd17b3, Star, and Sf-1. These findings indicate that LbGp plays an important role in enhancing testicular function and promoting testosterone synthesis.

Intensive care patients can experience significant long-term impairment in mobility and function caused by their critical illness. A potential contributory factor apart from critical illness polymyoneuropathy is the low levels of anabolic hormones in these patients. Testosterone levels in critically ill patients are extremely low, even in the latter recovery phase. A potential solution to critical illness myopathy may be to provide anabolic support in addition to standard care (early physiotherapy) to further improve gains in strength.

This project aims to test whether a synthetic testosterone (nandrolone) improves muscle strength in ICU survivors compared to placebo.

GAINS 2.0 is a multicentre, randomised, double blinded placebo-controlled trial which will allocate ICU patients in a 1:1 ratio to nandrolone compared to placebo which commenced recruitment in July 2023. Adult patients admitted to the ICU, receiving nutrition for a minimum of 24 hours with an ICU stay of at least 5 days, or patients with significant weakness as result of their ICU stay (such that they are unable to mobilise independently) will be eligible to participate. Sample size will be 54 patients. Patients will be randomised to receive nandrolone 100mg (males) / 50mg(females) weekly for 3 weeks in addition to standard care. The co-primary outcomes are the time to walking with one person assisting (Intensive Care Mobility scale = 8 or more, in days from randomisation), change in muscle strength measured by the Medical Research Council (MRC) muscle strength sum score from enrolment to hospital discharge and number of days out of hospital up to day 90 post-discharge. Secondary outcomes are grip strength measured by hand-held dynamometry. SF-36 scores (quality of life and functional domains), and days to return to work, for those working pre-ICU, will be collected via a 3-month phone follow-up.

A previous pilot feasibility trial showed that nandrolone is safe and feasible. We hypothesize nandrolone will improve muscle strength and physical functioning at hospital discharge and at follow-up. The results of this trial may have significant interest to clinicians and patients considering the large and increasing number of patients surviving intensive care but with physical impairment. This trial may have significant implications on lowering hospital costs and daily adjusted life years.

anzctr.org.au; No.: ACTRN12623000729628 URL: anzctr.org.au.

In the past decade, there has been a significant augmentation in the corpus of evidence pertaining to functional hypogonadism. Despite this, prevailing clinical guidelines continue to advise against the universal screening for hypogonadism in middle-aged and elderly males.

Numerous randomized controlled trials have scrutinized the effects of testosterone therapy in males afflicted with type 2 diabetes and/or obesity. However, these guidelines uniformly assert that lifestyle modifications and weight reduction should be the primary intervention strategies in overweight and obese males, relegating testosterone therapy to a secondary, selective option. It is extensively documented that testosterone therapy can yield substantial improvements in various metabolic parameters as well as ameliorate symptoms of erectile dysfunction. Moreover, recent studies have demonstrated the potential of testosterone therapy in reversing type 2 diabetes in males with low-normal testosterone levels who are at elevated risk for this condition, in comparison to the outcomes achievable through lifestyle modifications alone.

This focused review article aims to present a comprehensive update on the latest data concerning the innovative aspects of testosterone therapy in males with functional hypogonadism, particularly in the context of type 2 diabetes and/or obesity. Additionally, it will delve into the cardiovascular safety of such interventions within this high-risk demographic, with a special emphasis on insights gleaned from the TRAVERSE trial.

Secondary analyses of the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial revealed significantly higher rates of new-onset atrial fibrillation (AF) and acute kidney injury (AKI) in the testosterone replacement therapy (TRT) cohort.

To validate the secondary findings of the TRAVERSE trial.

We utilized the TriNetX Research Network to identify a cohort of men ages 45-80 years old who met similar inclusion criteria to the TRAVERSE trial. We compared hypogonadal men (testosterone 100-300 ng/dL) who had a prescription for topical testosterone therapy and men who did not. Propensity score matching was used to match patient populations. Kaplan Meier survival analysis was used to determine the relative risk of new-onset AF and AKI within 3 years.

New-onset AF and AKI within 3 years.

There were 2134 men included in each cohort after propensity score matching. Men on TRT had significantly lower testosterone (T) at the time of diagnosis compared to men not prescribed TRT (207 ± 66 ng/dL vs 246 ± 140 ng/dL, P < 0.001). Kaplan-Meier survival analysis showed a significantly increased risk of AKI among men on TRT (RR 1.53, 95% CI 1.07-2.18). However, TRT was not associated with a significantly increased risk of new-onset AF (RR 1.48, 95% CI 0.93-2.37).

Hypogonadal men with underlying cardiovascular risk factors or pre-existing cardiovascular disease who receive TRT may be at increased risk of AKI after starting therapy.

We evaluated a large global research database and utilized similar inclusion and exclusion to the TRAVERSE trial. However, our results are limited by the retrospective study design and reliance on documented claims data.

Similar to the TRAVERSE trial, our study demonstrated an increased risk of AKI among men on TRT, but did not find increased risk of AF. However, further studies are required to validate these results.

A paucity of studies addressed sex-related differences in clinical outcomes in the long term following acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). In these patients, it remains uncertain whether heart failure (HF) might exert a differential impact on the prognosis in the long term.

We queried a large-scale database of ACS patients undergoing PCI. The primary endpoint was new-onset HF. Secondary endpoints included mortality, myocardial infarction, re-PCI and ischaemic stroke. Propensity score matching was generated to balance group characteristics. A total of 3334 patients after propensity score matching were analysed. Follow-up was assessed at the 5 year term.

At 5 year follow-up, HF risk increased significantly in males versus females {17.9% vs. 14.8%, hazard ratio [HR] [95% confidence interval (CI)] = 1.22 [1.03-1.44], P = 0.02}. At 5 year follow-up, mortality was significantly higher in the male cohort as compared with the female cohort [HR (95% CI) = 1.23 (1.02-1.47), P = 0.02]. On landmark analysis, differences in mortality emerged after the first year and were maintained thereafter. Ischaemic outcomes were comparable between cohorts.

Following ACS, males experienced a greater long-term risk of developing new-onset HF as compared with females. This difference remained consistent across all prespecified subgroups. Mortality was significantly higher in males. No differences were observed in ischaemic outcomes. New-onset HF emerges as a primary contributor to long-term gender disparities after ACS and a strong predictor of mortality in men with HF.

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.

To characterize the relationship between testosterone replacement therapy (TRT) and anterior cruciate ligament (ACL) injuries.

A retrospective cohort study using a large insurance database was conducted. Patients who were prescribed TRT for at least 3 months were matched with controls who were not prescribed TRT. Rates of ACL tears were compared between the cohorts. Multiple subgroups were created based on age (<25 years, 25-35, 36-45, 46-55, 56-65, and 65+). Multivariable logistic regressions were performed to determine the association of TRT with ACL tears while accounting for demographic variables and comorbidities.

After matching, there were 160,839 patients in both the TRT cohort and control cohort. The incidence of ACL injuries was 17.8 per 10,000 person-years (95% CI: 16.4-19.2) for patients who were prescribed TRT and 4.9 per 10,000 person-years (95% CI: 4.1-5.7) for controls (p<0.001). Within 2 years of filling a testosterone prescription for at least 3 months, 572 (0.35%) patients experienced an ACL injury compared to only 157 (0.10%) controls during the same follow-up period (OR: 2.77; 95% CI: 2.26-3.42, p<0.001). When stratified by age, all groups except the <25 years of age group demonstrated significantly higher rate of ACL tears (OR 3.91-12.3, p<0.001-0.009). When separated by sex, males on TRT were 3.13 (95% CI: 2.50-3.93, p<0.001) times more likely while females on TRT were 1.94 (95% CI: 1.13-3.41, p=0.018) times more likely to experience an ACL injury compared to controls.

This study found that patients prescribed at least three months of TRT had a significantly higher incidence of ACL injuries compared to controls within a two-year follow-up period.

Level III, retrospective comparative study.

The Androgen Society is an international, multidisciplinary medical organization committed to advancing research and education in the field of testosterone deficiency and testosterone therapy (TTh). This position paper is written in response to results of the TRAVERSE study, published in June 2023, which reported no increased risk of major adverse cardiovascular events (MACE) in men who received TTh compared with placebo. In 2013-2014, 2 observational studies reported increased cardiovascular (CV) risks with TTh and received wide media attention. Despite strong criticism of those 2 studies, in 2015, the Food and Drug Administration added a CV warning to testosterone product labels and required pharmaceutical companies to perform a CV safety study, which became the TRAVERSE trial. TRAVERSE enrolled 5246 men at high risk for MACE based on existing heart disease or multiple risk factors. Participants were randomized to daily testosterone gel or placebo gel, with a mean follow-up of 33 months. Results revealed no greater risk of MACE (myocardial infarction, stroke, or CV death) or venothrombotic events in men who received TTh compared with placebo. Review of the prior literature reveals near uniformity of studies reporting no increased MACE with TTh. This includes 2 additional large randomized controlled trials, multiple smaller randomized controlled trials, several large observational studies, and 19 meta-analyses. In view of these findings, it is the position of the Androgen Society that it has now been conclusively determined that TTh is not associated with increased risks of heart attack, stroke, or CV death.

Organic male hypogonadism due to irreversible hypothalamic-pituitary-testicular (HPT) pathology is easily diagnosed and treated with testosterone-replacement therapy. However, controversy surrounds the global practice of prescribing testosterone to symptomatic men with low testosterone and non-gonadal factors reducing health status, such as obesity, type 2 diabetes, and ageing (ie, functional hypogonadism), but without identifiable HPT axis pathology. Health optimisation remains the gold-standard management strategy. Nevertheless, in the last decade large clinical trials and an individual patient data meta-analysis of smaller clinical trials confirmed that testosterone therapy induces modest, yet statistically significant, improvements in sexual function without increasing short-term to medium-term cardiovascular or prostate cancer risks in men with functional hypogonadism. Although testosterone improves bone mineral density and insulin sensitivity in these men, trials from the last decade suggest insufficient evidence to determine the safety and effectiveness of use of this hormone for the prevention of fractures or type 2 diabetes. This Review discusses the pathogenesis and diagnosis of male hypogonadism and appraises the evidence underpinning the management of this condition.

This review assesses the evidence of the physiological effects of testosterone on cardiovascular health, the association between male hypogonadism and cardiovascular health, and the effects of testosterone therapy on cardiovascular health in male hypogonadism. Preclinical studies suggest complex effects of testosterone on cardiovascular risk by acting on skeletal muscle, cardiomyocytes, vasculature, adipocytes, insulin action, and erythropoiesis. Furthermore, low testosterone has a bi-directional association with cardiometabolic risk. Observational studies have reported worse metabolic profiles in men with organic hypogonadism. However, a consistent association between major cardiovascular events and male hypogonadism has not been established. Hematocrit increases with testosterone therapy; however, most studies do not report an increase in venous thromboembolism risk. Although some observational studies and a small randomized controlled study reported an increased risk of cardiovascular disease, recent data confirm the medium-term cardiovascular safety of testosterone therapy in middle-aged and older men with low testosterone.

Male hypogonadism, which is characterized by low testosterone levels, has a significant impact on male sexual function, overall health, and fertility. Testosterone replacement therapy (TRT) is the conventional treatment for this condition, but it has potential adverse effects and is not suitable for men seeking to conceive. Testosterone plays an essential role in male sexual function, metabolism, mood, and overall well-being. Clomiphene citrate, a drug originally developed for female infertility, has recently gained attention as an off-label treatment for male hypogonadism. By blocking the negative feedback of estrogen on the hypothalamus and pituitary glands, clomiphene stimulates gonadotropin secretion, leading to increased endogenous testosterone production, which, in turn, improves sperm parameters and fertility and alleviates the symptoms of hypogonadism. Regarding the safety profile of clomiphene compared with TRT, clomiphene appears to confer a lower risk than TRT, which is associated with adverse effects such as polycythemia. Furthermore, combination therapy with clomiphene and anastrozole or human chorionic gonadotropin has been investigated as a potential approach to enhancing the effectiveness of treatments for improving hypogonadism symptoms. In conclusion, clomiphene citrate may offer a promising alternative to TRT for men with hypogonadism, particularly those desiring fertility preservations. However, its long-term efficacy and safety remain inadequately understood. Future research should focus on exploring the benefits of combination therapies and personalized treatment strategies based on individual patient characteristics.

Orthopaedic and sports medicine clinicians can improve outcomes for transgender patients by understanding the physiological effects of gender-affirming hormone therapy (GAHT). This narrative review investigated the role of GAHT on bone mineral density, fracture risk, thromboembolic risk, cardiovascular health and ligament/tendon injury in this population. A search from the PubMed database using relevant terms was performed. Studies were included if they were levels 1-3 evidence. Due to the paucity of studies on ligament and tendon injury risk in transgender patients, levels 1-3 evidence on the effects of sex hormones in cisgender patients as well as basic science studies were included for these two topics. This review found that transgender patients on GAHT have an elevated fracture risk, but GAHT has beneficial effects on bone mineral density in transgender women. Transgender women on GAHT also have an increased risk of venous thromboembolism, stroke and myocardial infarction compared with cisgender women. Despite these elevated risks, studies have found it is safe to continue GAHT perioperatively for both transgender women and men undergoing low-risk operations. Orthopaedic and sports medicine clinicians should understand these unique health considerations for equitable patient care.

Primary hypogonadism is a recognised complication in survivors of testicular cancer. However, secondary hypogonadism can result from other causes that suppress the hypothalamic-pituitary axis, including obesity, high dose glucocorticoids, chronic end organ failure, and diabetes. The aim of this study was to explore low total serum testosterone in Australian survivors of testicular cancer and examine associations with body mass index, age, and prior chemotherapy use.

Clinical data including height, weight, diagnosis, treatment, and hormonal evaluations during follow-up were extracted from the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Chemocog study (2007-2012), accompanied by data from two Australian, high-volume testicular cancer centres included in the iTestis testicular cancer registry (2012-2019). Low testosterone was defined by a serum concentration of testosterone (T) < 10 nmol/L, and was classified as primary by a serum concentration of luteinising hormone (LH) > 8 IU/L, otherwise as secondary.

Two hundred eighty-five individuals with either stage 1 or advanced testicular cancer were included. Of these, 105 (37%) were treated with orchidectomy and chemotherapy. Forty-nine (17%) met criteria for low testosterone during follow-up: 21 (43%) had primary and 27 (55%) had secondary low testosterone. Survivors of testicular cancer with higher body mass index were more likely to display low testosterone, both primary (p = 0.032) and secondary (p = 0.028). Our data did not show evidence of an association between older age or chemotherapy use and low testosterone in our cohort.

Low total serum testosterone was common in survivors of testicular cancer, and associated with a higher body mass index prior to orchidectomy, suggesting that elevated body mass index may contribute to low testosterone in this population, and that body weight, diet, and exercise should be addressed in testicular cancer follow-up.

Most prostate cancers express the androgen receptor (AR), and tumor growth and progression are facilitated by exceptionally low levels of systemic or intratumorally produced androgens. Thus, absolute inhibition of the androgen signaling axis remains the goal of current therapeutic approaches to treat prostate cancer (PCa). Paradoxically, high dose androgens also exhibit considerable efficacy as a treatment modality in patients with late-stage metastatic PCa. Here we show that low levels of androgens, functioning through an AR monomer, facilitate a non-genomic activation of the mTOR signaling pathway to drive proliferation. Conversely, high dose androgens facilitate the formation of AR dimers/oligomers to suppress c-MYC expression, inhibit proliferation and drive a transcriptional program associated with a differentiated phenotype. These findings highlight the inherent liabilities in current approaches used to inhibit AR action in PCa and are instructive as to strategies that can be used to develop new therapeutics for this disease and other androgenopathies.

Testosterone supplementation has increased in recent years for both treatment of hypogonadism and recreational use. Strokes in young adults have similarly increased with a larger proportion of patients in this age group having a stroke due to early onset of cardiovascular risk factors or unrelated to conventional risks. Hormonal treatments are associated with increased stroke risk amongst women, with some studies indicating an increase in stroke risk as high as 40% when compared to non-users. However, less is known about male sex hormones and risks associated with increased stroke. Limited data evaluates the relationship between testosterone supplementation and stroke in young adults. In this review, we analyze the literature and plausible underlying pathophysiological mechanisms associated with increased risks in patients using exogenous testosterone. Furthermore, we highlight the gaps in research about safety and long-term effects on young patients.

Hypogonadism is a risk factor for cardiovascular disease (CVD) in men related, in part, to increased oxidative stress. Elevated large artery stiffness and central pulsatile hemodynamics (e.g., pulse pressure and wave reflection magnitude) are independent risk factors for CVD. However, whether large artery stiffness and central pulsatile hemodynamics are (1) elevated in hypogonadal men independent of traditional CVD risk factors and (2) related to increased oxidative stress is unknown. Young men (N = 23; 30 ± 4 years) and middle-aged/older (MA/O) men with normal (> 400-1000 ng/dL; n = 57; 59 ± 7 years) or low testosterone (< 300 ng/dL; n = 21; 59 ± 7 years) underwent assessments of large artery stiffness (carotid ß-stiffness via ultrasonography) and central pulsatile hemodynamics (pulse wave analysis; SphygmoCor XCEL) following an infusion of saline or vitamin C to test the tonic suppression of vascular function by oxidative stress. Carotid stiffness differed by age (p < 0.001) and gonadal status within MA/O men (low testosterone vs. normal testosterone: 9.3 ± 0.7 vs. 8.0 ± 0.3U, p = 0.036). Central pulsatile hemodynamics did not differ by age or gonadal status (p > 0.119). Vitamin C did not alter carotid stiffness in any group (p > 0.171). There was a significant group × infusion interaction on aortic reflection magnitude (p = 0.015). Vitamin C treatment reduced aortic reflection magnitude in young and MA/O men with normal testosterone (both p < 0.001) but not MA/O men with low testosterone (p = 0.891). Collectively, hypogonadism may accelerate age-related large artery stiffening in MA/O men with low testosterone, independent of CVD risk factors; however, this is not related to increased reactive oxygen species sensitive to an acute vitamin C infusion.

Personalized medicine represents a novel and integrative approach that focuses on an individual's genetics and epigenetics, precision medicine, lifestyle and exposures as key players of health status and disease phenotypes.

In this narrative review, we aim to carefully discuss the current knowledge on gender disparities in cardiometabolic diseases, and we consider the sex- specific expression of miRNAs and their role as promising tool in precision medicine.

Personalised medicine overcomes the restricted care of patient based on a binomial sex approach, by enriching itself with a holistic and dynamic gender integration. Recognized as a major worldwide health emergency, cardiometabolic disorders continue to rise, impacting on health systems and requiring more effective and targeted strategies. Several sex and gender drivers might affect the onset and progression of cardiometabolic disorders in males and females at multiple levels. In this respect, distinct contribution of genetic and epigenetic mechanisms, molecular and physiological pathways, sex hormones, visceral fat and subcutaneous fat and lifestyle lead to differences in disease burden and outcomes in males and females.

Sex and gender play a pivotal role in precision medicine because the influence the physiology of each individual and the way they interact with environment from intrauterine life.

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.

Anabolic androgenic steroids (AAS) are disproportionately used by sexual minority men, with the physical and mental health implications of AAS use incompletely understood.

To understand the reasons for use and health care needs of gay, bisexual, and queer cisgender men using AAS.

This qualitative study was conducted from November 2021 to May 2023 using self-administered questionnaires and semistructured interviews that were transcribed and coded using reflexive thematic analysis. Participants were recruited through convenience and snowball sampling from lesbian, gay, bisexual, transgender, and queer clinical centers in New York, New York, as well as through online platforms. All patients self-identified as cisgender and gay, bisexual, or queer.

History of nonprescribed AAS use for a minimum of 8 consecutive weeks was required.

The primary outcomes were reasons for and health implications of AAS use and interactions with health care practitioners, as determined through interviews. Interview transcripts were collected and analyzed.

Thematic saturation was reached after interviews with 12 male participants (mean [SD] age, 44 [11] years), with the majority of participants identifying as gay (10 participants [83%]), White non-Hispanic (9 participants [75%]), being in their 30s and 40s (9 participants [75%]), holding a bachelor's degree or higher (11 participants [92%]), and having used steroids for a mean (SD) of 7.5 (7.1) years. One participant (8%) self-identified as Black, and 2 (17%) identified as Hispanic. Seven men (58%) met the criteria for muscle dysmorphia on screening. Nine overarching themes were found, including internal and external motivators for initial use, continued use because of effectiveness or fear of losses, intensive personal research, physical and emotional harms experienced from use, using community-based harm reduction techniques, frustration with interactions with the medical community focused on AAS cessation, and concerns around the illegality of AAS.

In this qualitative study, AAS use among cisgender gay, bisexual, and queer men was found to be associated with multifactorial motivators, including a likely AAS use disorder and muscle dysmorphia. Despite all participants experiencing harms from use, men seeking medical help found insufficient support with practitioners insistent on AAS cessation and, thus, developed their own harm reduction techniques. Further research is needed to assess the utility of practitioner education efforts, the safety and efficacy of community-developed harm reduction methods, and the impact of AAS decriminalization on health care outcomes for this patient population.

The cardiovascular (CV) safety of testosterone (T) replacement therapy (TRT) is still conflicting. Recent data suggested a TRT-related increased risk of atrial fibrillation (AF). The aim of this study was to systematic review and meta-analyze CV risk related to TRT as derived from placebo controlled randomized trials (RCTs).

An extensive Medline, Embase, and Cochrane search was performed. All placebo-controlled RCTs reporting data on TRT-related CV safety were considered. To better analyze the role of T on AF, population-based studies investigating the relationship between endogenous circulating T levels and AF incidence were also included and analyzed.

Out of 3.615, 106 studies were considered, including 8.126 subjects treated with TRT and 7.310 patients allocated to placebo. No difference between TRT and placebo was observed when major adverse CV events were considered. Whereas the incidence of non-fatal arrhythmias and AF was increased in the only trial considering CV safety as the primary endpoint, this was not confirmed when all other studies were considered (MH-OR 1.61[0.84;3.08] and 1.44[0.46;4.46]). Similarly, no relationship between endogenous T levels and AF incidence was observed after the adjustment for confounders Available data confirm that TRT is safe and it is not related to an increased CV risk.

The debate over the cardiovascular (CV) implications of testosterone therapy (TT) have resulted in diverging safety recommendations and clinical guidelines worldwide. This narrative review synthesizes and critically evaluates long-term studies examining the effects of TT within the context of aging, obesity, and endogenous sex hormones on CV disease (CVD) risk to support informed clinical decision-making. Observational studies have variably linked low endogenous testosterone with increased CVD risk, while randomized controlled trials (RCTs) demonstrate that TT yields cardiometabolic benefits without increasing short-term CV risk. The TRAVERSE trial, as the first RCT powered to assess CVD events, did not show increased major adverse cardiac events (MACE) incidence; however, its limitations - specifically the maintenance of testosterone at low-normal levels, a high participant discontinuation rate, and short follow-up - warrant a careful interpretation of its results. Furthermore, findings from the TTrials cardiovascular sub-study, which showed an increase in non-calcified plaque, indicate the need for ongoing research into the long-term CV impact of TT. The decision to initiate TT should consider the current evidence gaps, particularly for older men with known CVD. The CV effects of maintaining physiological testosterone levels through exogenous means remain to be fully explored. Until more definitive evidence is available, clinical practice should prioritize individualized care and informed discussions on the potential CV implications of TT.

This work aimed to evaluate the effects of the aqueous extract of Vepris afzelii roots on a rat model of hypogonadism. Phytochemical screening and acute toxicity of the extract were performed using different procedures. Hypogonadism was induced orally in adult Wistar rats using cyproterone acetate (30 mg/kg) for ten days. Besides six normal rats (10 ml/kg of distilled water, normal control), 30 hypogonadal rats were subdivided into five groups of six animals each, receiving for 14 days: distilled water (10 ml/kg, hypogonadal control), testosterone (4 mg/kg/3days) and the extract of V. afzelii (100, 200 and 400 mg/kg). Sexual behavior, sperm parameters, testes function and structure were assessed. Compared to the normal controls, significant (p = 0.0000) increases in mount (24 ± 0.94 seconds vs. 1200 ± 00 seconds) and intromission (49.16 ± 10.85 seconds vs. 1200 ± 00 seconds) latencies, and post-ejaculatory interval (381.72 ± 37.55 seconds vs. 1200 ± 00 seconds) were observed in all groups receiving cyproterone acetate on day 0. Total inhibitions of mounts (63.50 ± 8.91 vs. 00 ± 00), intromissions (36.66 ± 3.51 vs. 00 ± 00) (p = 0.0000), ejaculations (2.83 ± 00 vs. 00 ± 00, p = 0.0002) frequencies and mean copulatory interval (627.30 ± 81.80 vs. 00 ± 00, p = 0.0000) were also observed in these groups. Moreover, decreases in daily sperm production (2.65 ± 0.19 vs. 1.17 ± 0.08, p = 0.0498), percentage of sperm mobility (78.64 ± 8.41 vs. 10.12 ± 2.32), serum testosterone level (8.39 ± 0.63 ng/dl vs. 1.68 ± 0.19 ng/dl), diameter of seminiferous tubules (111.97 ± 0.51 µm vs. 94.51 ± 0.57 µm) and height of germinal epithelium (46.58 ± 0.34 µm vs. 33.74 ± 0.66 µm) (p = 0.0000) associated with increases in sperm transit (3.13 ± 0.45 vs. 11.07 ± 1.45, p = 0.0000) were also observed in these groups. Interestingly, compared to hypogonadal control and day 0, the administration of V. afzelii extract induced significant (p = 0.0000) improvements in all these altered parameters with 400 mg/kg being the most active dose. These results, attributed to saponins, flavonoids, polyphenols and triterpenes detected in this plant's extract confirm its traditional usage and could be useful for the management of patients suffering from hypogonadism.

Testosterone therapy for men with testosterone deficiency is widely used, yet remains controversial. The rich and fascinating history of the testicles, including human castration, provides a valuable perspective on this important topic.

This study reviewed the history of testosterone from antiquity to the modern day.

Primary sources consisted of books and relevant articles, augmented by a MEDLINE search using the key words "testis," "testicles," "castration," "eunuchs," "testosterone," and "testicular function."

An early scientific observation was that castration reduced sexual development and activity, originating with domestication of animals approximately 10 000 years ago. Human castration appears in ancient Egyptian mythology more than 4000 years ago, in Greek mythology from 8th century BCE, and in the Bible. The history of eunuchs in China spanned 2000 years, beginning with the Hsia dynasty (2205-1766 BCE). The concept that the testicles produced some factor responsible for male sexual development and behavior was thus known throughout the world since the beginning of recorded history. Testosterone was isolated and synthesized in 1935 and was soon available as a treatment. Multiple benefits of testosterone therapy were apparent by 1940. Recent large, controlled testosterone studies have conclusively demonstrated sexual and general health benefits, with a strong safety profile.

Testosterone has been a known substance for <1% of the historical timeline, yet knowledge that the testes were responsible for male sexual development and behavior has been known since the beginning of recorded history. Today, modern evidence has demonstrated the importance of normal levels of testosterone for general health as well as sexual function and desire. Yet, testosterone therapy remains controversial. We believe this historical review provides a helpful perspective on this age-old issue.

Maternal hyperandrogenism during pregnancy is associated with adverse gestational outcomes and chronic non-communicable diseases in offspring. However, few studies are reported to demonstrate the association between maternal androgen excess and cardiac health in offspring. This study aimed to explore the relation between androgen exposure in utero and cardiac health of offspring in fetal and adult period. Its underlying mechanism is also illustrated in this research.

Pregnant mice were injected with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was collected for metabolite and morphological analysis. The hearts from adult offspring were also collected for morphological and qPCR analysis. H9c2 cells were treated with 75 μM androsterone. Immunofluorescence, flow cytometry, qPCR, and western blot were performed to observe cell proliferation and explore the underlying mechanism.

Intrauterine exposure to excessive androgen led to thinner ventricular wall, decreased number of cardiomyocytes in fetal offspring and caused cardiac hypertrophy, compromised cardiac function in adult offspring. The analysis of steroid hormone metabolites in fetal heart tissue by ultra performance liquid chromatography and tandem mass spectrometry showed that the content of androgen metabolite androsterone was significantly increased. Mechanistically, H9c2 cells treated with androsterone led to a significant decrease in phosphorylated retinoblastoma protein (pRB) and cell cycle-related protein including cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin D1 (CCND1) in cardiomyocytes. This resulted in cell cycle arrest at G1-S phase, which in turn inhibited cardiomyocyte proliferation.

Taken together, our results indicate that in utero exposure to DHT, its metabolite androsterone could directly decrease cardiomyocytes proliferation through cell cycle arrest, which has a life-long-lasting effect on cardiac health. Our study highlights the importance of monitoring sex hormones in women during pregnancy and the follow-up of cardiac function in offspring with high risk of intrauterine androgen exposure.

To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT) <12 nmol l -1 , we performed a meta-analysis following the Population Intervention Comparison Outcome model. Population: men with TT <12 nmol l -1 or clear mention of hypogonadism in the inclusion criteria of patients; intervention: TRT; comparison: placebo or no therapy; outcomes: arterial thrombotic events (stroke, myocardial infarction [MI], upper limbs, and lower limbs), VTE (deep vein thrombosis [DVT], portal vein thrombosis, splenic thrombosis, and pulmonary embolism), and mortality. A total of 2423 abstracts were assessed for eligibility. Twenty-four studies, including 14 randomized controlled trials (RCTs), were finally included, with a total of 4027 and 310 288 hypotestosteronemic male patients, from RCTs and from observational studies, respectively. Based on RCT-derived data, TRT did not influence the risk of arterial thrombosis (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 0.47-3.43, P = 0.64), stroke (OR = 1.34, 95% CI: 0.09-18.97, P = 0.83), MI (OR = 0.51, 95% CI: 0.11-2.31, P = 0.39), VTE (OR = 1.42, 95% CI: 0.22-9.03, P = 0.71), pulmonary embolism (OR = 1.38, 95% CI: 0.27-7.04, P = 0.70), and mortality (OR = 0.70, 95% CI: 0.20-2.38, P = 0.56). Meanwhile, when only observational studies are considered, a significant reduction in the risk of developing arterial thrombotic events, MI, venous thromboembolism, and mortality was observed. The risk for DVT remains uncertain, due to the paucity of RCT-based data. TRT in men with TT <12 nmol l -1 is safe from the risk of adverse cardiovascular events. Further studies specifically assessing the risk of DVT in men on TRT are needed.

Hormone therapy (HT) is important and frequently used both regarding replacement therapy (HRT) and gender affirming therapy (GAHT). While HRT has been effective in addressing symptoms related to hormone shortage, several side effects have been described. In this context, there are some studies that show increased cardiovascular risk. However, there are also studies reporting protective aspects of HT. Nevertheless, the exact impact of HT on cardiovascular risk and the underlying mechanisms remain poorly understood. This article explores the relationship between diverse types of HT and cardiovascular risk, focusing on mechanistic insights of the underlying hormones on platelet and leukocyte function as well as on effects on endothelial and adipose tissue cells.

Sex hormones are hypothesized to drive sex-specific health disparities. Here, we study the association between sex steroid hormones and DNA methylation-based (DNAm) biomarkers of age and mortality risk including Pheno Age Acceleration (AA), Grim AA, and DNAm-based estimators of Plasminogen Activator Inhibitor 1 (PAI1), and leptin concentrations. We pooled data from three population-based cohorts, the Framingham Heart Study Offspring Cohort, the Baltimore Longitudinal Study of Aging, and the InCHIANTI Study, including 1,062 postmenopausal women without hormone therapy and 1,612 men of European descent. Sex-stratified analyses using a linear mixed regression were performed, with a Benjamini-Hochberg (BH) adjustment for multiple testing. Sex Hormone Binding Globulin (SHBG) was associated with a decrease in DNAm PAI1 among men (per 1 standard deviation (SD): -478 pg/mL; 95%CI: -614 to -343; P:1e-11; BH-P: 1e-10), and women (-434 pg/mL; 95%CI: -589 to -279; P:1e-7; BH-P:2e-6). The testosterone/estradiol (TE) ratio was associated with a decrease in Pheno AA (-0.41 years; 95%CI: -0.70 to -0.12; P:0.01; BH-P: 0.04), and DNAm PAI1 (-351 pg/mL; 95%CI: -486 to -217; P:4e-7; BH-P:3e-6) among men. In men, testosterone was associated with a decrease in DNAm PAI1 (-481 pg/mL; 95%CI: -613 to -349; P:2e-12; BH-P:6e-11). SHBG was associated with lower DNAm PAI1 among men and women. Higher testosterone and testosterone/estradiol ratio were associated with lower DNAm PAI and a younger epigenetic age in men. A decrease in DNAm PAI1 is associated with lower mortality and morbidity risk indicating a potential protective effect of testosterone on lifespan and conceivably cardiovascular health via DNAm PAI1.

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.

Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT remain controversial. An updated systematic review and meta-analysis aimed to determine the effectiveness and security of TRT treating for LOH.

Randomized controlled trials (RCTs) of TRT for LOH were searched in the databases of Pubmed, Embase, Clinicaltrials.gov and Cochrane from 1990 to 2023 and an updated meta-analysis was conducted.

The results of 28 RCTs involving 3461 patients were included and scrutinized in this analysis. Among these, 11 RCTs were of long-term duration (≥12 months), while 18 RCTs were short-term studies (<12 months) comparing TRT with a placebo. TRT modalities comprised injection, oral administration, and transdermal administration. International Index of Erectile Function (IIEF) (Weighted Mean difference (WMD) 3.26; 95%; 95% confidence interval (CI) 1.65-4.88; P<0.0001) was obviously improved in the TRT group. International Prostate Symptom Score (IPSS) (WMD 0.00; 95% CI -0.45-0.45; P=1.0), Prostate Volume (PV) (WMD 0.38; 95% CI -0.64-1.41; P=0.46), Maximum Flow Rate (Qmax) (WMD 1.86; 95% CI -0.98-4.69; P=0.20), Postvoid Residual Urine Volume (PVR) (WMD 3.20; 95% CI -5.87-12.28; P=0.49) and Prostate-Specific Antigen (PSA) (WMD 0.08; 95% CI -0.00-0.17; P=0.06) were not significantly statistical between two groups.

This meta-analysis reveals that TRT could improve the IIEF score of hypogonadal men without detriment to the IPSS score, PV, Qmax, PVR and PSA regardless of the administration method or duration of treatment.The meta-analysis was registered at PROSPERO (CRD42023413434).

Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction.

To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction.

We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023.

We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone.

Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes.

We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS.

In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.

Anabolic steroid use at supraphysiologic doses has been associated with an increased risk of tendon injury. However, the musculoskeletal effects of testosterone therapy in the clinical setting are not well understood.

(1) Is prescription testosterone associated with a higher odds of subsequent quadriceps muscle or tendon injury? (2) Is prescription testosterone associated with a higher odds of surgical repair of the quadriceps tendon?

The PearlDiver Database, which contains data on Medicaid, Medicare, and commercially insured patients, allows for a large representative sample of the US population including both publicly and privately insured patients. The database was queried for all patients between 2011 and 2018 who filled a testosterone prescription. Additionally, all quadriceps injuries using ICD-9 and ICD-10 codes between 2011 and 2018 were queried. Propensity score matching based on age, sex, Charlson comorbidity index, and specific comorbidities allowed us to create matched control groups. We used the t-test and chi-square analysis to compare the unmatched and matched cohorts. A total of 151,797 patients (123,627 male patients and 28,170 female patients) with a history of filled testosterone prescriptions were included in the study after matching with the control group, which was of equal size and representation of age, male-female proportions, and comorbidities. Chi-square and logistic regression analyses were performed to compare odds of quadriceps injury and quadriceps tendon repair among the testosterone groups to that of their respective control groups by age and sex.

Within 1 year of filling prescriptions for testosterone, 0.06% (97 of 151,797) of patients experienced a quadriceps injury compared with less than 0.01% (18 of 151,797) of patients in the control group (OR 5.4 [95% CI 3.4 to 9.2]; p < 0.001). Within the sex-specific matched groups, filling a testosterone prescription was associated with an increase in the odds of quadriceps injury in male patients within 1 year of the prescription (OR 5.8 [95% CI 3.5 to 10.3]; p < 0.001). Additionally, patients who filled a testosterone prescription were at increased risk of having quadriceps tendon repair within a year of the injury than were patients in the matched control group (OR 4.7 [95% CI 2.0 to 13.8]; p = 0.001).

Considering these findings, it is important for physicians to counsel patients receiving testosterone replacement therapy of the substantially increased odds of quadriceps tendon injury. Future investigations into the mechanisms of influence of exogenous anabolic steroids on tendon injury remains of interest.

Level III, therapeutic study.

As an increasingly popular therapeutic option, testosterone replacement therapy (TRT) has gained significant notoriety for its health benefits in indicated populations, such as those suffering from hypogonadism.

Benefits such as improved libido, muscle mass, cognition, and quality of life have led to widened public interest in testosterone as a health supplement. No therapy exists without side effects; testosterone replacement therapy has been associated with side effects such as an increased risk of polycythemia, benign prostate hypertrophy (BPH), prostate cancer, gynecomastia, testicular atrophy, and infertility. Testosterone replacement therapy is often accompanied by several prophylactic co-therapies aimed at reducing the prevalence of these side effects. Literature searches for sections on the clinical benefits and risks associated with TRT were performed to include clinical trials, meta-analyses, and systematic reviews from the last 10 years.

Data from clinical studies over the last decade suggest that the benefits of this therapy outweigh the risks and result in overall increased quality of life and remission of symptoms related to hypogonadism. With this in mind, the authors of this review suggest that carefully designed clinical trials are warranted for the investigation of TRT in symptomatic age-related hypogonadism.

To investigate the impact of testosterone replacement therapy (TRT) on cardiovascular outcomes in hypogonadal men.

A meta-analysis of 26 randomized controlled trials involving 10 941 participants was conducted. Various clinical outcomes, including all-cause mortality, cardiovascular-related mortality, myocardial infarction, stroke, congestive heart failure, atrial fibrillation, pulmonary embolism, and venous thrombosis, were assessed.

No statistically significant differences were observed between the TRT group and the control group in terms of these clinical outcomes. Sensitivity analysis and publication bias assessment supported the robustness of the findings. Meta-regression analysis found no significant associations between clinical outcomes and potential covariates, including age, diabetes, hypertension, dyslipidemia, and smoking.

Previous research on TRT and cardiovascular events, with comparisons to studies like the Testosterone Trials and the studies conducted by Vigen et al, Finkle et al, Layton et al, and Wallis et al, is provided. The significance of the systematic review and meta-analysis approach is emphasized, particularly its exclusive focus on hypogonadal patients.

This study offers reassurance that TRT does not increase mortality risk or worsen cardiovascular outcomes in hypogonadal men. However, further research, especially long-term studies involving diverse populations, is essential to strengthen the evidence base and broaden the applicability of these findings.

Sexual dysfunction is a common but underestimated disorder of diabetic patients of both genders, entailing specific and complex pathogenesis and severely affecting reproductive health and quality of life. Hyperglycemia, dyslipidemia, hypertension, obesity, aging, and psychological factors underlie its pathogenesis. A large body of evidence indicates that advanced glycation end products and oxidative stress have a distinct impact on the pathogenesis of diabetes and its complications, including hypogonadism, which is closely related to sexual dysfunction. Advanced glycation end products seem to affect sexual function either directly by accumulation in various regions of the reproductive system and/or correlation or indirectly through oxidative stress induction via several mechanisms. They are also involved in the pathogenesis of diabetic complications, which are related to sexual dysfunction. Herein, we review the issue of sexual dysfunction in diabetic males and females, with special emphasis on the impact of advanced glycation end products in the pathogenesis of sexual dysfunction, the relationship of advanced glycation end products with low testosterone levels in diabetic subjects, which account for the proportion of disorder and the available therapeutic interventions.

The T4DM study randomized 1007 men with impaired glucose tolerance or newly diagnosed diabetes to testosterone undecanoate (TU, 1000 mg) or matching placebo (P) injections every 12 weeks for 24 months with a lifestyle program with testosterone (T) treatment reducing diabetes diagnosis by 40%.

The long-term effects on new diagnosis of diabetes, cardiovascular and prostate disease, sleep apnea, weight maintenance trajectory and androgen dependence were not yet described.

A follow-up email survey after a median of 5.1 years since last injection obtained 599 (59%) completed surveys (316 T, 283 P), with participants in the follow-up survey compared with nonparticipants in 23 anthropometric and demographic variables.

Randomization to was TU associated with stronger belief in study benefits during (64% vs 49%, P < .001) but not after the study (44% vs 40%, P = .07); there is high interest in future studies. At T4DM entry, 25% had sleep apnea with a new diagnosis more frequent on TU (3.0% vs 0.4%, P = .03) during, but not after, the study. Poststudy, resuming prescribed T treatment was more frequent among TU-treated men (6% vs 2.8%, P = .03). Five years after cessation of TU treatment there was no difference in self-reported rates of new diagnosis of diabetes, and prostate or cardiovascular disease, nor change in weight maintenance or weight loss behaviors.

We conclude that randomized T treatment for 24 months in men with impaired glucose tolerance or new diabetes but without pathological hypogonadism was associated with higher levels of self-reported benefits and diagnosis of sleep apnea during, but not after, the study as well as more frequent prescribed poststudy T treatment consistent with androgen dependence in some men receiving prolonged injectable TU.

Testosterone (T), the principal androgen secreted by the testes, plays an essential role in male health. Male hypogonadism is diagnosed based on a combination of associated clinical signs and symptoms and laboratory confirmation of low circulating T levels. In this review, we have highlighted factors, both biological and analytical, that introduce variation into the measurement of serum T concentrations in men; these need to be considered when requesting T levels and interpreting results. There is an ongoing need for analytical standardisation of T assays and harmonisation of pre- and post-analytical laboratory practices, particularly in relation to the laboratory reference intervals provided to clinicians. Further, there is a need to share with service users the most up-to-date and evidence-based action thresholds for serum T as recommended in the literature. Estimation of free testosterone may be helpful. Causes of secondary hypogonadism should be considered. A comprehensive approach is required in the management of male hypogonadism, including lifestyle modification as well as medication where appropriate. The goal of treatment is the resolution of symptoms as well as the optimisation of metabolic, cardiovascular, and bone health. The advice of an endocrinologist should be sought when there is doubt about the cause and appropriate management of the hypogonadism.

Immediate thrombolysis in submassive pulmonary embolism on the basis of bedside echocardiography can be a lifesaving decision in areas where computed tomography (CT) pulmonary angiogram is not readily available.

Bedside echocardiography can be a rapid diagnostic and decision-making tool for immediate thrombolysis in submassive pulmonary embolism with evidence of progressively failing ventricles. We report a case of submassive pulmonary embolism in a 26-year-old male under testosterone replacement therapy, who was successfully thrombolyzed based on bedside echocardiography findings.