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–go...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.展开更多
Bite force is an important performance indicator of individual fitness that is closely related to food acquisition,male competition,and mating selection.It is also affected by a variety of factors and different mechan...Bite force is an important performance indicator of individual fitness that is closely related to food acquisition,male competition,and mating selection.It is also affected by a variety of factors and different mechanisms.Therefore,it is relatively difficult to understand the evolutionary driving forces of changes in bite force.In this study,the driving factors affecting the bite force of wild-derived red junglefowl(Gallus gallus jabouillei)were investigated from the aspects of morphological indicators and physiological characteristics.Results showed that the bite force of wild-derived red junglefowl was directly related to sex,showing obvious sexual differences.However,there was no correlation between the plasma testosterone level and bite force.The bite force of males was significantly greater than that of females,and the body index(i.e.,PC1 of five body measures,namely body mass,body length,wing length,tail length,and tarsus length),the grasp index(i.e.,tomial length×bill width)of males were significantly greater than those of females.Sexual selection may have played a key role in the evolution of bite force in the red junglefowl.Future studies should examine other key factors affecting changes in bite force to verify the correlation between secondary sexual characteristics and bite force in red junglefowls.展开更多
The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for th...The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.展开更多
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 I^(-1),we performed a meta-analysis foll...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 I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome model.Population:men with TT<12 nmol I^(-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 310288 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,Ml,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 I^(-1) is safe from the risk of adverse cardiovascular events.Further studies specifically assessing the risk of DVT in men on TRT are needed.展开更多
An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of...An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer);that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes;(2) association between endogenous testosterone density and the tumor load;and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature’s results.展开更多
Individuals with inflammatory bowel disease(IBD)have been reported to be at an increased risk of infertility and sexual dysfunction.Although the relationship between them remains unclear,IBD severity is suspected to a...Individuals with inflammatory bowel disease(IBD)have been reported to be at an increased risk of infertility and sexual dysfunction.Although the relationship between them remains unclear,IBD severity is suspected to affect hormone levels and fertility.To analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD(UC-IBD),we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital,Medan,Indonesia.The patients were classified into three groups based on the Mayo score for Uc,followed by a comparison of various semen and hormone parameters among these groups.In addition to the cross-sectional analysis,a simple correlation test was conducted irrespective of the patient grouping.Sperm concentration,motility,and morphology were found to decline significantly with an increase in IBD severity.Without classifying patients with IBD into subgroups,the Mayo score showed negative correlations with sperm concentration(r=-0.375,P<0.0001),rapid progressive motility(r=-0.660,P<0.0001),free testosterone(r=-0.732,P<0.0001),and total testosterone(r=-0.721,P<0.0001),and positivecorrelations with immotile sperm(r=0.660,P<0.0001),abnormal morphology(r=0.657,P<0.0001),and sex hormone-binding globulin(SHBG;r=0.278,P=0.002).Sperm concentration,motility,and morphology declined significantly with the severity of IBD.This study suggests a significant negative impact of IBD severityonsemenqualityand sexhormones.展开更多
OBJECTIVE:To determine the therapeutic effects of the Zhuangyao Jianshen pill(壮腰健肾丸,ZYJSP)against benign prostatic hyperplasia(BPH)and investigate the underlying mechanism.METHODS:Forty-eight male Sprague-Dawley ...OBJECTIVE:To determine the therapeutic effects of the Zhuangyao Jianshen pill(壮腰健肾丸,ZYJSP)against benign prostatic hyperplasia(BPH)and investigate the underlying mechanism.METHODS:Forty-eight male Sprague-Dawley rats were randomly divided into six groups:Control group,BPH model group,finasteride-treated group,ZYJSP low,medium and high dose groups.Except for the control group,40 rats were castrated and injected with testosterone propionate(TP)for 28 consecutive day to induce BPH.Meanwhile,the corresponding drugs were administered by gavage.The prostate wet weight,prostate index(PI),and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH.Levels of the serum sex hormones,oxidative stress markers,inflammatory markers,renal function markers,growth factors,and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH.RESULTS:ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats.TP markedly increased the levels of creatinine,blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate.Most of these markers were significantly decreased by ZYJSP.ZYJSP significantly restored the dysregulation of testosterone,estradiol,and dihydrotestosterone caused by TP.Furthermore,ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6,interleukin-8,and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum.CONCLUSION:These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats,and the underlying mechanism might be related to regulating sex hormone balance,reducing oxidative stress,and inhibiting the inflammatory response.展开更多
AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers ...AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.展开更多
This current review highlights adiponectin engagement with AdipoR1 and AdipoR2 which subsequently triggers pathways such as AMPK,PPARα,and MAPK,thereby modulating testicular steroidogenesis.Adiponectin's actions ...This current review highlights adiponectin engagement with AdipoR1 and AdipoR2 which subsequently triggers pathways such as AMPK,PPARα,and MAPK,thereby modulating testicular steroidogenesis.Adiponectin's actions on Leydig and adrenal cells inhibit androgen secretion by suppressing the steroidogenic acute regulatory protein(StAR).Given that StAR facilitates cholesterol to testosterone conversion,AMPK inhibits this process by modulating cholesterol transport and suppressing StAR expression through multiple avenues.Furthermore,adiponectin-induced PPARαactivation impedes mitochondrial cholesterol influx,further modulating androgen biosynthesis.The suppressive influence of PPARαon steroidogenic genes,notably StAR,is evident.Collectively,adiponectin signalling predominantly attenuates androgen production,ensuring metabolic and reproductive equilibrium.Imbalances,as seen in conditions like hypogonadism and obesity-related infertility,highlight their crucial roles and potential clinical interventions for reproductive disorders.展开更多
Objective:To investigate the successive morphological stages of spermatogenesis,hormonal regulation,and testosterone profile in dromedary camel reproduction.Methods:Testicular tissue samples were obtained from 12 drom...Objective:To investigate the successive morphological stages of spermatogenesis,hormonal regulation,and testosterone profile in dromedary camel reproduction.Methods:Testicular tissue samples were obtained from 12 dromedary bull camels aged 7 to 8 at a local abattoir.The histological assessment involved tissue processing,hematoxylin and eosin(H&E)staining,and examination under a microscope.Stereological analysis,germ cell identification,and assessment of seminiferous tubules and maturation were conducted.Testosterone assay was performed by radioimmunoassay using blood samples collected at regular intervals.Results:The study revealed 12 phases of the dromedary camel's seminiferous epithelium cycle,highlighting distinct morphological characteristics and cellular processes.Acrosomal migration,maturation,cap formation,and the Golgi-mediated synthesis of proacrosomal vesicles were also explained in dimension,as were the steps of acrosome biogenesis.Spermatids and mature sperm cells were present when spermatogenesis phases were examined.An analysis of the dimensions of seminiferous tubules revealed specific measures for diameter,area,and epithelial height about luminal characteristics.Moreover,there were noticeable variations in the serum testosterone concentrations during the study period,indicating temporal dynamics.Conclusions:This study outlines the spermatogenesis process in dromedary camels across 12 stages,emphasizing cellular dynamics and acrosomal biogenesis.It also provides seminiferous tubule measurements and observes seasonal testosterone fluctuations,offering insights into reproductive regulation and potential strategies for camel breeding conservation.展开更多
Controversies surround the usefulness of identifying patients with the metabolic syndrome （MetS）. Many of the components are accepted risk factors for cardiovascular disease （CVD）. Although the MetS as defined inc...Controversies surround the usefulness of identifying patients with the metabolic syndrome （MetS）. Many of the components are accepted risk factors for cardiovascular disease （CVD）. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone （TT） and sex hormone binding globulin （SHBG） levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin Alc levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.展开更多
Testosterone deficiency is common in men with cardiovascular disease （CVD）, and randomized placebo-controlled trials （RCTs） have reported beneficial effects of testosterone therapy on exercise-induced cardiac isch...Testosterone deficiency is common in men with cardiovascular disease （CVD）, and randomized placebo-controlled trials （RCTs） have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise （VO2m,x） and muscle strength in chronic heart failure （CHF）, shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade （L-calcium channel） and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2m=x and vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the insulin receptor, glucose transporters, and expression on regulatory enzymes of key metabolic pathways. The effect on high-density lipoprotein-cholesterol （HDL-C） differs between studies in that it has been found to fall, rise, or have no change in levels. Testosterone replacement can suppress the levels of circulating pro-inflammatory cytokines and stimulate the production of interleukin-lO （IL-IO） which has anti-inflammatory and anti-atherogenic actions in men with CVD. No effect on C-reactive protein has been detected. No adverse effects on clotting factors have been detected. RCTs have not clearly demonstrated any significant evidence that testosterone improves or adversely affects the surrogate markers of atherosclerosis such as reduction in carotid intima thickness or coronary calcium deposition. Any effect of testosterone on prevention or amelioration of atherosclerosis is likely to occur over years as shown in statin therapy trials and not months as used in testosterone RCTs. The weight of evidence from long-term epidemiological studies supports a protective effect as evidenced by a reduction in major adverse CV events （MACEs） and mortality in studies which have treated men with testosterone deficiency, No RCT where testosterone has been replaced to the normal healthy range has reported a significant benefit or adverse effect on MACE nor has any recent meta-analysis.展开更多
Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure （CHF） have yielded conflicting results. The aim of this study was to examine the relationship betwe...Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure （CHF） have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men （age ≥60 years） with CHF were recruited. Total testosterone （TI＇） and sex hormone-binding globulin （SHBG） were measured, and estimated free testosterone （eFT） was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol I^-1 （230 ng dI^-1）, 27 had an eFT level below 0.225 nmol I^-1 （65 pg ml^-1） and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% （38/175） and 27.4% （48/175）, respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction （LVEF） and N-terminal pro-brain natriuretic peptide （NT-pro-BNP） （all P〈0.01）. Kaplan-Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate （both P〈0.01 by log-rank test）. However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time （0R=0.97, 95% CI： 0.84-1.12, P=0.28 and 0R=0.92, 95% CI： 0.82-1.06, P=0.14, respectively）. Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.展开更多
The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgeni...The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids （AAS） within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal （HPG） axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.展开更多
Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used f...Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.展开更多
As men grow older, circulating testosterone declines while the incidence of cardiovascular disease increases. Thus, the role of sex hormones as biomarkers, and possibly contributing factors to clinical manifestations ...As men grow older, circulating testosterone declines while the incidence of cardiovascular disease increases. Thus, the role of sex hormones as biomarkers, and possibly contributing factors to clinical manifestations of cardiovascular disease in the increasing demographic of aging men, has attracted considerable interest. This review focuses on observational studies of endogenous androgens, namely circulating testosterone and dihydrotestosterone, which have examined their associations with cardiovascular events such as myocardial infarction and stroke. Studies which have examined the associations of endogenous estrogens, namely circulating estradiol, with these outcomes are also discussed. In large prospective cohort studies of predominantly middle-aged and older men, lower circulating testosterone consistently predicts higher incidence of cardiovascular events. Of note, both lower circulating testosterone and lower dihydrotestosterone are associated with higher incidence of stroke. These associations are less apparent when myocardial infarction is considered as the outcome. Results for estradiol are inconsistent. Lower circulating testosterone has been shown to predict higher cardiovascular disease-related mortality, as has lower circulating dihydrotestosterone. It is possible that the relationship of circulating androgens to cardiovascular events or mortality outcomes may be U-shaped rather than linear, with an optimal range defining men at lowest risk. Epidemiological studies are observational in nature and do not prove causality. Associations observed in studies of endogenous androgens need not necessarily translate into similar effects of exogenous androgens. Rigorous randomized controlled trials are needed to clarify the effects of testosterone treatment on cardiovascular risk in men.展开更多
Benign prostatic hyperplasia （BPH） is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents ...Benign prostatic hyperplasia （BPH） is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract （MFME） improves BPH, using the testosterone propionate （TP）-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP （3 mg kg-1） dissolved in corn oil, for 4 weeks. MFME was administered daily by oral garage at a dose of 200 mg kg-1 for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight （prostate/body weight ratio） was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone （DHT） in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound（s） responsibility for inducing the protective effect against BPH and determine its mechanism of action,展开更多
Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with appa...Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavai lable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men （mean age： 52.8--- 9.3 years） not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log （sex hormone） levels and log （coronary calcium score） after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ~〉 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score （P=0.046） after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein （HDL） cholesterol, hypertension medication and hyperlipidernia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not （P=0.674, P=O. 121 and P=O. 102, respectively）. Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.展开更多
This study aimed to investigate the effect of intramuscular injection of testosterone undecanoate on overall quality of life （QoL） in men with testosterone deficiency syndrome （TDS）. A randomized controlled trial ...This study aimed to investigate the effect of intramuscular injection of testosterone undecanoate on overall quality of life （QoL） in men with testosterone deficiency syndrome （TDS）. A randomized controlled trial over a 12-month period was carried out in 2009. One hundred and twenty men aged 40 years and above with a diagnosis of TDS （serum total testosterone 〈12 nmol 1-1 and total Aging Male Symptom （AMS） scores ≥ 27） were invited to participate. Interventions comprised intramuscular injection of either placebo or 1000 mg testosterone undecanoate, given at weeks O, 6, 18, 30 and 42. This paper presents the secondary analysis of QoL changes measured in the scores of Short-Form-12 （SF-12） scale at baseline, weeks 30 and 48 after the first injection. A total of 56/60 and 58/60 men from the active treatment and placebo group, respectively, completed the study. At week 48, before adjusting for baseline differences, the QoL of men in the treatment group improved significantly in five out of the eight domains on SF-12. The physical health composite scores improved 4.0 points from a baseline of 41.9±7.0 in the treatment group compared to 0.8 point from a baseline of 43.7--7.1 in the placebo group （F=3.652, P=0.027）. The mental health composite scores improved 4.4 points from a baseline of 37.1±9.0 in the treatment group compared to 1.0 points from a baseline of 37.6±7.9 in the placebo group （F=4.514, P=-0.018）. After adjusting for baseline differences, significant improvement was observed in mental health composite scores, but not in physical health composite scores. LQng-acting testosterone undecanoate significanUy improved the mental health component of QoL in men with TDS.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves ins...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.展开更多
文摘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.
基金supported by the National Natural Science Foundation of China(no.31800320 and no.32360250 to XR)Natural Science Foundation of Hainan Province(no.320RC506 to XR)+3 种基金funded by the project supported by the Scientific Research start-up Fund of Hainan University[no.KYQD(ZR)20057]the Teaching Research of Hainan University(no.Hdsz20-9)supported by Hainan Tropical Rainforest Conservation Research Project,ZDYF2023RDYL01(supported by the Hainan Institute of National Park,HINP,KY-24ZK02)supported by the specific research fund of The Innovation Platform for Academicians of Hainan Province.
文摘Bite force is an important performance indicator of individual fitness that is closely related to food acquisition,male competition,and mating selection.It is also affected by a variety of factors and different mechanisms.Therefore,it is relatively difficult to understand the evolutionary driving forces of changes in bite force.In this study,the driving factors affecting the bite force of wild-derived red junglefowl(Gallus gallus jabouillei)were investigated from the aspects of morphological indicators and physiological characteristics.Results showed that the bite force of wild-derived red junglefowl was directly related to sex,showing obvious sexual differences.However,there was no correlation between the plasma testosterone level and bite force.The bite force of males was significantly greater than that of females,and the body index(i.e.,PC1 of five body measures,namely body mass,body length,wing length,tail length,and tarsus length),the grasp index(i.e.,tomial length×bill width)of males were significantly greater than those of females.Sexual selection may have played a key role in the evolution of bite force in the red junglefowl.Future studies should examine other key factors affecting changes in bite force to verify the correlation between secondary sexual characteristics and bite force in red junglefowls.
基金supported by grants from the National Natural Science Foundation of China(N0.82474525 and No.82074444)the Hunan Provincial Natural Outstanding Young People Science Foundation(2023JJ10032)the Hunan Province Health and High-Level Talent Medical Academic Leader Training Plan(20240304051).
文摘The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.
文摘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 I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome model.Population:men with TT<12 nmol I^(-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 310288 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,Ml,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 I^(-1) is safe from the risk of adverse cardiovascular events.Further studies specifically assessing the risk of DVT in men on TRT are needed.
文摘An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer);that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes;(2) association between endogenous testosterone density and the tumor load;and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature’s results.
文摘Individuals with inflammatory bowel disease(IBD)have been reported to be at an increased risk of infertility and sexual dysfunction.Although the relationship between them remains unclear,IBD severity is suspected to affect hormone levels and fertility.To analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD(UC-IBD),we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital,Medan,Indonesia.The patients were classified into three groups based on the Mayo score for Uc,followed by a comparison of various semen and hormone parameters among these groups.In addition to the cross-sectional analysis,a simple correlation test was conducted irrespective of the patient grouping.Sperm concentration,motility,and morphology were found to decline significantly with an increase in IBD severity.Without classifying patients with IBD into subgroups,the Mayo score showed negative correlations with sperm concentration(r=-0.375,P<0.0001),rapid progressive motility(r=-0.660,P<0.0001),free testosterone(r=-0.732,P<0.0001),and total testosterone(r=-0.721,P<0.0001),and positivecorrelations with immotile sperm(r=0.660,P<0.0001),abnormal morphology(r=0.657,P<0.0001),and sex hormone-binding globulin(SHBG;r=0.278,P=0.002).Sperm concentration,motility,and morphology declined significantly with the severity of IBD.This study suggests a significant negative impact of IBD severityonsemenqualityand sexhormones.
文摘OBJECTIVE:To determine the therapeutic effects of the Zhuangyao Jianshen pill(壮腰健肾丸,ZYJSP)against benign prostatic hyperplasia(BPH)and investigate the underlying mechanism.METHODS:Forty-eight male Sprague-Dawley rats were randomly divided into six groups:Control group,BPH model group,finasteride-treated group,ZYJSP low,medium and high dose groups.Except for the control group,40 rats were castrated and injected with testosterone propionate(TP)for 28 consecutive day to induce BPH.Meanwhile,the corresponding drugs were administered by gavage.The prostate wet weight,prostate index(PI),and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH.Levels of the serum sex hormones,oxidative stress markers,inflammatory markers,renal function markers,growth factors,and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH.RESULTS:ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats.TP markedly increased the levels of creatinine,blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate.Most of these markers were significantly decreased by ZYJSP.ZYJSP significantly restored the dysregulation of testosterone,estradiol,and dihydrotestosterone caused by TP.Furthermore,ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6,interleukin-8,and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum.CONCLUSION:These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats,and the underlying mechanism might be related to regulating sex hormone balance,reducing oxidative stress,and inhibiting the inflammatory response.
文摘AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.
文摘This current review highlights adiponectin engagement with AdipoR1 and AdipoR2 which subsequently triggers pathways such as AMPK,PPARα,and MAPK,thereby modulating testicular steroidogenesis.Adiponectin's actions on Leydig and adrenal cells inhibit androgen secretion by suppressing the steroidogenic acute regulatory protein(StAR).Given that StAR facilitates cholesterol to testosterone conversion,AMPK inhibits this process by modulating cholesterol transport and suppressing StAR expression through multiple avenues.Furthermore,adiponectin-induced PPARαactivation impedes mitochondrial cholesterol influx,further modulating androgen biosynthesis.The suppressive influence of PPARαon steroidogenic genes,notably StAR,is evident.Collectively,adiponectin signalling predominantly attenuates androgen production,ensuring metabolic and reproductive equilibrium.Imbalances,as seen in conditions like hypogonadism and obesity-related infertility,highlight their crucial roles and potential clinical interventions for reproductive disorders.
文摘Objective:To investigate the successive morphological stages of spermatogenesis,hormonal regulation,and testosterone profile in dromedary camel reproduction.Methods:Testicular tissue samples were obtained from 12 dromedary bull camels aged 7 to 8 at a local abattoir.The histological assessment involved tissue processing,hematoxylin and eosin(H&E)staining,and examination under a microscope.Stereological analysis,germ cell identification,and assessment of seminiferous tubules and maturation were conducted.Testosterone assay was performed by radioimmunoassay using blood samples collected at regular intervals.Results:The study revealed 12 phases of the dromedary camel's seminiferous epithelium cycle,highlighting distinct morphological characteristics and cellular processes.Acrosomal migration,maturation,cap formation,and the Golgi-mediated synthesis of proacrosomal vesicles were also explained in dimension,as were the steps of acrosome biogenesis.Spermatids and mature sperm cells were present when spermatogenesis phases were examined.An analysis of the dimensions of seminiferous tubules revealed specific measures for diameter,area,and epithelial height about luminal characteristics.Moreover,there were noticeable variations in the serum testosterone concentrations during the study period,indicating temporal dynamics.Conclusions:This study outlines the spermatogenesis process in dromedary camels across 12 stages,emphasizing cellular dynamics and acrosomal biogenesis.It also provides seminiferous tubule measurements and observes seasonal testosterone fluctuations,offering insights into reproductive regulation and potential strategies for camel breeding conservation.
文摘Controversies surround the usefulness of identifying patients with the metabolic syndrome （MetS）. Many of the components are accepted risk factors for cardiovascular disease （CVD）. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone （TT） and sex hormone binding globulin （SHBG） levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin Alc levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.
文摘Testosterone deficiency is common in men with cardiovascular disease （CVD）, and randomized placebo-controlled trials （RCTs） have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise （VO2m,x） and muscle strength in chronic heart failure （CHF）, shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade （L-calcium channel） and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2m=x and vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the insulin receptor, glucose transporters, and expression on regulatory enzymes of key metabolic pathways. The effect on high-density lipoprotein-cholesterol （HDL-C） differs between studies in that it has been found to fall, rise, or have no change in levels. Testosterone replacement can suppress the levels of circulating pro-inflammatory cytokines and stimulate the production of interleukin-lO （IL-IO） which has anti-inflammatory and anti-atherogenic actions in men with CVD. No effect on C-reactive protein has been detected. No adverse effects on clotting factors have been detected. RCTs have not clearly demonstrated any significant evidence that testosterone improves or adversely affects the surrogate markers of atherosclerosis such as reduction in carotid intima thickness or coronary calcium deposition. Any effect of testosterone on prevention or amelioration of atherosclerosis is likely to occur over years as shown in statin therapy trials and not months as used in testosterone RCTs. The weight of evidence from long-term epidemiological studies supports a protective effect as evidenced by a reduction in major adverse CV events （MACEs） and mortality in studies which have treated men with testosterone deficiency, No RCT where testosterone has been replaced to the normal healthy range has reported a significant benefit or adverse effect on MACE nor has any recent meta-analysis.
文摘Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure （CHF） have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men （age ≥60 years） with CHF were recruited. Total testosterone （TI＇） and sex hormone-binding globulin （SHBG） were measured, and estimated free testosterone （eFT） was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol I^-1 （230 ng dI^-1）, 27 had an eFT level below 0.225 nmol I^-1 （65 pg ml^-1） and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% （38/175） and 27.4% （48/175）, respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction （LVEF） and N-terminal pro-brain natriuretic peptide （NT-pro-BNP） （all P〈0.01）. Kaplan-Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate （both P〈0.01 by log-rank test）. However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time （0R=0.97, 95% CI： 0.84-1.12, P=0.28 and 0R=0.92, 95% CI： 0.82-1.06, P=0.14, respectively）. Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.
文摘The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids （AAS） within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal （HPG） axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.
文摘Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.
文摘As men grow older, circulating testosterone declines while the incidence of cardiovascular disease increases. Thus, the role of sex hormones as biomarkers, and possibly contributing factors to clinical manifestations of cardiovascular disease in the increasing demographic of aging men, has attracted considerable interest. This review focuses on observational studies of endogenous androgens, namely circulating testosterone and dihydrotestosterone, which have examined their associations with cardiovascular events such as myocardial infarction and stroke. Studies which have examined the associations of endogenous estrogens, namely circulating estradiol, with these outcomes are also discussed. In large prospective cohort studies of predominantly middle-aged and older men, lower circulating testosterone consistently predicts higher incidence of cardiovascular events. Of note, both lower circulating testosterone and lower dihydrotestosterone are associated with higher incidence of stroke. These associations are less apparent when myocardial infarction is considered as the outcome. Results for estradiol are inconsistent. Lower circulating testosterone has been shown to predict higher cardiovascular disease-related mortality, as has lower circulating dihydrotestosterone. It is possible that the relationship of circulating androgens to cardiovascular events or mortality outcomes may be U-shaped rather than linear, with an optimal range defining men at lowest risk. Epidemiological studies are observational in nature and do not prove causality. Associations observed in studies of endogenous androgens need not necessarily translate into similar effects of exogenous androgens. Rigorous randomized controlled trials are needed to clarify the effects of testosterone treatment on cardiovascular risk in men.
文摘Benign prostatic hyperplasia （BPH） is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract （MFME） improves BPH, using the testosterone propionate （TP）-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP （3 mg kg-1） dissolved in corn oil, for 4 weeks. MFME was administered daily by oral garage at a dose of 200 mg kg-1 for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight （prostate/body weight ratio） was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone （DHT） in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound（s） responsibility for inducing the protective effect against BPH and determine its mechanism of action,
文摘Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavai lable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men （mean age： 52.8--- 9.3 years） not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log （sex hormone） levels and log （coronary calcium score） after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ~〉 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score （P=0.046） after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein （HDL） cholesterol, hypertension medication and hyperlipidernia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not （P=0.674, P=O. 121 and P=O. 102, respectively）. Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.
文摘This study aimed to investigate the effect of intramuscular injection of testosterone undecanoate on overall quality of life （QoL） in men with testosterone deficiency syndrome （TDS）. A randomized controlled trial over a 12-month period was carried out in 2009. One hundred and twenty men aged 40 years and above with a diagnosis of TDS （serum total testosterone 〈12 nmol 1-1 and total Aging Male Symptom （AMS） scores ≥ 27） were invited to participate. Interventions comprised intramuscular injection of either placebo or 1000 mg testosterone undecanoate, given at weeks O, 6, 18, 30 and 42. This paper presents the secondary analysis of QoL changes measured in the scores of Short-Form-12 （SF-12） scale at baseline, weeks 30 and 48 after the first injection. A total of 56/60 and 58/60 men from the active treatment and placebo group, respectively, completed the study. At week 48, before adjusting for baseline differences, the QoL of men in the treatment group improved significantly in five out of the eight domains on SF-12. The physical health composite scores improved 4.0 points from a baseline of 41.9±7.0 in the treatment group compared to 0.8 point from a baseline of 43.7--7.1 in the placebo group （F=3.652, P=0.027）. The mental health composite scores improved 4.4 points from a baseline of 37.1±9.0 in the treatment group compared to 1.0 points from a baseline of 37.6±7.9 in the placebo group （F=4.514, P=-0.018）. After adjusting for baseline differences, significant improvement was observed in mental health composite scores, but not in physical health composite scores. LQng-acting testosterone undecanoate significanUy improved the mental health component of QoL in men with TDS.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.
