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Nutrition and Health Jun 2023A recent meta-analysis found low-carbohydrate, high-protein diets (> 3.4 g/kg of bodyweight/day) (g/kg/day) decreased men's total testosterone (∼5.23 nmol/L)... (Meta-Analysis)
Meta-Analysis
A recent meta-analysis found low-carbohydrate, high-protein diets (> 3.4 g/kg of bodyweight/day) (g/kg/day) decreased men's total testosterone (∼5.23 nmol/L) [Whittaker and Harris (2022) Low-carbohydrate diets and men's cortisol and testosterone: systematic review and meta-analysis. . DOI: 10.1177/02601060221083079]. This finding has generated substantial discussion, however, it has often lacked clarity and context, with the term 'high-protein' being used unqualified. Firstly, diets < 3.4 g/kg/day are not associated with a consistent decrease in testosterone. Secondly, the average protein intake is ∼1.3 g/kg/day, conventional 'high-protein' diets are ∼1.8-3 g/kg/day and the vast majority of athletes are < 3.4 g/kg/day; meaning very few individuals will ever surpass 3.4 g/kg/day. To avoid such confusion in the future, the following definitions are proposed: very high (> 3.4 g/kg/day), high (1.9-3.4 g/kg/day), moderate (1.25-1.9 g/kg/day) and low (<1.25 g/kg/day). Using these, very high-protein diets (> 3.4 g/kg/day) appear to decrease testosterone, however high- and moderate-protein diets (1.25-3.4 g/kg/day) do not.
Topics: Male; Humans; Testosterone; Body Weight; Diet, Carbohydrate-Restricted; Nutritional Status; Diet, High-Protein
PubMed: 36266956
DOI: 10.1177/02601060221132922 -
Food and Chemical Toxicology : An... Jun 2023Information in the published literature indicates that consumption of CBD can result in developmental and reproductive toxicity and hepatotoxicity outcomes in animal... (Review)
Review
Information in the published literature indicates that consumption of CBD can result in developmental and reproductive toxicity and hepatotoxicity outcomes in animal models. The trend of CBD-induced male reproductive toxicity has been observed in phylogenetically disparate organisms, from invertebrates to non-human primates. CBD has also been shown to inhibit various cytochrome P450 enzymes and certain efflux transporters, resulting in the potential for drug-drug interactions and cellular accumulation of xenobiotics that are normally transported out of the cell. The mechanisms of CBD-mediated toxicity are not fully understood, but they may involve disruption of critical metabolic pathways and liver enzyme functions, receptor-specific binding activity, disruption of testosterone steroidogenesis, inhibition of reuptake and degradation of endocannabinoids, and the triggering of oxidative stress. The toxicological profile of CBD raises safety concerns, especially for long term consumption by the general population.
Topics: Animals; Humans; Male; Cannabidiol; Cytochrome P-450 Enzyme System; Carrier Proteins; Drug Interactions; Testosterone
PubMed: 37088127
DOI: 10.1016/j.fct.2023.113799 -
JAMA Oncology Jun 2023Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial.
OBJECTIVE
To determine in men with oligometastatic prostate cancer whether the addition of MDT to intermittent hormone therapy improves oncologic outcomes and preserves time with eugonadal testosterone compared with intermittent hormone therapy alone.
DESIGN, SETTING, PARTICIPANTS
The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a phase 2, basket randomized clinical trial for multiple solid tumors testing the addition of MDT to standard-of-care systemic therapy. Men aged 18 years or older with oligometastatic prostate cancer who had 5 or fewer metastases and were treated with hormone therapy for 2 or more months were enrolled to the prostate intermittent hormone therapy basket at multicenter tertiary cancer centers from September 2018 to November 2020. The cutoff date for the primary analysis was January 7, 2022.
INTERVENTIONS
Patients were randomized 1:1 to MDT, consisting of definitive radiation therapy to all sites of disease and intermittent hormone therapy (combined therapy arm; n = 43) or to hormone therapy only (n = 44). A planned break in hormone therapy occurred 6 months after enrollment, after which hormone therapy was withheld until progression.
MAIN OUTCOMES AND MEASURES
The primary end point was disease progression, defined as death or radiographic, clinical, or biochemical progression. A key predefined secondary end point was eugonadal progression-free survival (PFS), defined as the time from achieving a eugonadal testosterone level (≥150 ng/dL; to convert to nanomoles per liter, multiply by 0.0347) until progression. Exploratory measures included quality of life and systemic immune evaluation using flow cytometry and T-cell receptor sequencing.
RESULTS
The study included 87 men (median age, 67 years [IQR, 63-72 years]). Median follow-up was 22.0 months (range, 11.6-39.2 months). Progression-free survival was improved in the combined therapy arm (median not reached) compared with the hormone therapy only arm (median, 15.8 months; 95% CI, 13.6-21.2 months) (hazard ratio, 0.25; 95% CI, 0.12-0.55; P < .001). Eugonadal PFS was also improved with MDT (median not reached) compared with the hormone therapy only (6.1 months; 95% CI, 3.7 months to not estimable) (hazard ratio, 0.32; 95% CI, 0.11-0.91; P = .03). Flow cytometry and T-cell receptor sequencing demonstrated increased markers of T-cell activation, proliferation, and clonal expansion limited to the combined therapy arm.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, PFS and eugonadal PFS were significantly improved with combination treatment compared with hormone treatment only in men with oligometastatic prostate cancer. Combination of MDT with intermittent hormone therapy may allow for excellent disease control while facilitating prolonged eugonadal testosterone intervals.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03599765.
Topics: Male; Humans; Aged; Quality of Life; Prostatic Neoplasms; Progression-Free Survival; Prostate; Testosterone
PubMed: 37022702
DOI: 10.1001/jamaoncol.2023.0161 -
Nutrients Sep 2023Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the... (Review)
Review
Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all -random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.
Topics: Child; Humans; Cholesterol, LDL; Cross-Sectional Studies; Diet, Ketogenic; Drug Resistant Epilepsy; Multimorbidity; Reproducibility of Results; Seizures; Testosterone; Treatment Outcome; Meta-Analysis as Topic
PubMed: 37836444
DOI: 10.3390/nu15194161 -
The Journal of Clinical Endocrinology... Oct 2023Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital...
CONTEXT
Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), a rare autosomal recessive disorder characterized by cortisol deficiency and androgen excess due to elevated adrenocorticotropin.
OBJECTIVE
To evaluate the safety, tolerability, and efficacy of crinecerfont in adolescents with 21OHD CAH.
METHODS
This was an open-label, phase 2 study (NCT04045145) at 4 centers in the United States. Participants were males and females, 14 to 17 years of age, with classic 21OHD CAH. Crinecerfont was administered orally (50 mg twice daily) for 14 consecutive days with morning and evening meals. The main outcomes were change from baseline to day 14 in circulating concentrations of ACTH, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone.
RESULTS
8 participants (3 males, 5 females) were enrolled; median age was 15 years and 88% were Caucasian/White. After 14 days of crinecerfont, median percent reductions from baseline to day 14 were as follows: ACTH, -57%; 17OHP, -69%; and androstenedione, -58%. In female participants, 60% (3/5) had ≥50% reduction from baseline in testosterone.
CONCLUSION
Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH.
Topics: Male; Adult; Humans; Female; Adolescent; Androgens; Adrenal Hyperplasia, Congenital; Androstenedione; 17-alpha-Hydroxyprogesterone; Testosterone; Adrenocorticotropic Hormone
PubMed: 37216921
DOI: 10.1210/clinem/dgad270 -
JAMA Network Open Dec 2023
Topics: Humans; Testosterone; Testosterone Congeners; Nutritional Status; Iodine
PubMed: 38117501
DOI: 10.1001/jamanetworkopen.2023.48573 -
Frontiers in Endocrinology 2023According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive... (Review)
Review
According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering from depression. The most common sexual manifestations are decreased libido, erectile dysfunction and orgasmic disorder. In addition, epidemiological studies have documented a reduction of testosterone concentrations in men with depression and, for these reasons, depressive disorders appear as one possible cause of male functional hypogonadism. Moreover, some largely used antidepressant medications can cause or worsen sexual complaints, thus depression and its treatments rise several andrological-relevant issues. The other way round, men with hypogonadism can manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond to testosterone replacement therapy (TRT). However, the prevalence of functional hypogonadism in depression, and of depressive symptoms in hypogonadal men, is not known. Severe depressive symptoms do not respond to TRT, while the effect of treating major depression on functional hypogonadism, has not been investigated. Overall, the clinical relevance of each condition to the other, as well as the physiopathological underpinnings of their relationship, are still to be clarified. The present review summarizes current evidence on the influence of testosterone on mood and of depression on the hypothalamic-pituitary-testis axis; the clinical association between male hypogonadism and depression; and the reciprocal effects of respective treatments.
Topics: Adult; Humans; Male; Depression; Testosterone; Behavior Therapy; Depressive Disorder, Major; Hypogonadism
PubMed: 37635965
DOI: 10.3389/fendo.2023.1198437 -
Endocrine Journal Jul 2023Testosterone plays a key role in the maintenance of physical and mental functions in men. Age-related testosterone decline is closely associated with sarcopenia and...
Testosterone plays a key role in the maintenance of physical and mental functions in men. Age-related testosterone decline is closely associated with sarcopenia and muscle deterioration, while testosterone decline is linked with the etiology and prevention of diseases such as angina pectoris, arteriosclerosis, obesity, metabolic syndrome, and dementia. Late-onset hypogonadism (LOH) is defined as a disease characterized by age-related testosterone decline and associated clinical symptoms. Testosterone replacement therapy improves health-related QOL in patients with LOH.
Topics: Male; Humans; Testosterone; Men's Health; Quality of Life; Hypogonadism; Obesity; Hormone Replacement Therapy; Aging
PubMed: 37045775
DOI: 10.1507/endocrj.EJ22-0604 -
Atherosclerosis Nov 2023The population of people identifying as transgender has grown rapidly in recent years, resulting in a substantive increase in individuals obtaining gender-affirming... (Review)
Review
The population of people identifying as transgender has grown rapidly in recent years, resulting in a substantive increase in individuals obtaining gender-affirming medical care to align their secondary sex characteristics with their gender identity. This has established benefits for patients including improvements in gender dysphoria and psychosocial functioning, while reducing adverse mental health outcomes. Despite these potential advantages, recent evidence has suggested that gender-affirming hormone therapy (GAHT) may increase the risk of cardiovascular disease. However, owing to a paucity of research, the mechanisms underpinning these increased risks are poorly understood. Moreover, previous research has been limited by heterogenous methodologies, being underpowered, and lacking appropriate control populations. Consequently, the need for evidence regarding cardiovascular health in LGBTQ + individuals has been recognised as a critical area for future research to facilitate better healthcare and guidance. Recent research investigating the effect of transmasculine (testosterone) GAHT on cardiovascular disease risk points to testosterone effecting the nitric oxide pathway, triggering inflammation, and promoting endothelial dysfunction. Equivalent studies focussing on transfeminine (oestrogen) GAHT are required, representing a crucial area of future research. Furthermore, when examining the effects of GAHT on the vasculature, it cannot be ignored that there are multiple factors that may increase the burden of cardiovascular disease in the transgender population. Such stressors include major psychological stress; increased adverse health behaviours, such as smoking; discrimination; and lowered socioeconomic status; all of which undoubtedly impact upon cardiovascular disease risk and offers the opportunity for intervention.
Topics: Female; Male; Humans; Transgender Persons; Cardiovascular Diseases; Gender Identity; Vascular Diseases; Testosterone
PubMed: 37821271
DOI: 10.1016/j.atherosclerosis.2023.117282