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
Serum testosterone concentration levels were measured in 27 female patients with ovarian masses and n 8 female patients with malignant gastrointestinal tumors. The serum testasterone levels were found to be a more spe...Serum testosterone concentration levels were measured in 27 female patients with ovarian masses and n 8 female patients with malignant gastrointestinal tumors. The serum testasterone levels were found to be a more specific marker,compared with other methods, in the differential diagnosis of primary and metastatic tumors(P<0.01).Serum testosterone was at abnormally high levels inpatients with Krukenberg tumors assoiated with signet cells and luteinized stroma cells, but fell to very low levels after oophoiectomy. Testosterone levels were normal showever in patients with poorly-differentiated metastatic ovarisn tumors, or with gastro-intestinal cancers not involving the ovaries.We also found that testosaterone levels in patients with mucinous adenocarcinoma of either ovary or of the gastro-intestinal tract were higher than in patients with other types of tumor(P<0.05).展开更多
背景:传统观察性研究难以揭露烧伤与生物标志物间的潜在因果关系,孟德尔随机化凭借遗传变异作为工具变量模拟随机对照试验的优势,成为解析复杂疾病因果关联的重要工具。目的:基于孟德尔随机化方法探讨烧伤与41种炎症因子和35种血液和尿...背景:传统观察性研究难以揭露烧伤与生物标志物间的潜在因果关系,孟德尔随机化凭借遗传变异作为工具变量模拟随机对照试验的优势,成为解析复杂疾病因果关联的重要工具。目的:基于孟德尔随机化方法探讨烧伤与41种炎症因子和35种血液和尿液标志物的关系。方法:①烧伤的完整全基因组关联研究数据在IEU open gwas project数据库(由英国The University of Bristol构建)中获取,该数据包括了218131例样本,16380465个单核苷酸多态性;②41种炎症因子数据来源于芬兰青年心血管风险研究数据库(由图尔库大学应用和预防心血管医学研究中心构建)一项8293人的研究数据;③35种血液和尿液生物标志物数据来源于英国生物样本库(由英国政府、惠康基金会和英国医学研究理事会共同发起的大型生物医学数据库项目)(n=363228人)。以单核苷酸多态性作为工具变量,利用逆方差加权、MR Egger、加权中位数和加权模式的方法进行分析。采用Cochrane’s Q检验来识别结果的异质性,MR Egger截距检验和MR-PRESSO检验及“留一法”检验等评估暴露-结局关联的可靠性。结果与结论:烧伤降低了白细胞介素9(OR=0.97;95%CI,0.949 to 0.997;P=0.030)和睾酮(OR=0.997;95%CI,0.995 to 0.999;P=0.025)水平,且不存在异质性和水平多效性,证明了结果的稳健性。研究通过孟德尔随机化分析表明,烧伤后白细胞介素9和睾酮水平降低,提示提高白细胞介素9和睾酮水平可能有助于烧伤后组织修复和改善蛋白质分解速率。展开更多
With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwis...With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular （HPT） axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.展开更多
To investigate the effect of arsenic on spermatogenesis. Methods: Mature (4 months old) Wistar rats were intraperitoneally administered sodium arsenite at doses of 4, 5 or 6 mg-kg^-day1 for 26 days. Different varietie...To investigate the effect of arsenic on spermatogenesis. Methods: Mature (4 months old) Wistar rats were intraperitoneally administered sodium arsenite at doses of 4, 5 or 6 mg-kg^-day1 for 26 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), lutuneizing hormone (LH), testosterone and assessment of the epididymal sperm count. Results: In the 5 and 6 mg/kg groups, there were significant dose-dependent decreases in the accessory sex organ weights, epididymal sperm count and plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII. The changes were insignificant in the 4 mg/kg group. Conclusion: Arsenite has a suppressive influence on spermatogenesis and gonadotrophin and testosterone release in rats.展开更多
Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm ...Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone （LH） secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin （SHBG）, or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea （OSA） appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure （CPAP） does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.展开更多
Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function a...Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day （n = 10 mice per dose）. Control animals （n = 10） received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein （STAR）, cytochrome P450 cholesterol side-chain cleavage enzyme （P450scc）, and 3β-hydroxysteroid dehydrogenase （3βHSD） in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone （ITT） concentration also increased in the VAP-treated groups. The expression of STAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis （STAR, P450scc, and 3β-HSD） and the following promotion of testosterone syothesis in vivo.展开更多
Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats...Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.展开更多
The aim of this study was to explore the effects of varicocele on the morphology and function of Leydig cells in the rat testis. Forty male Sprague-Dawley rats were divided into two groups： the experimental group und...The aim of this study was to explore the effects of varicocele on the morphology and function of Leydig cells in the rat testis. Forty male Sprague-Dawley rats were divided into two groups： the experimental group underwent surgery to create a left varicocele （VC）, and the control group underwent a sham operation. Serum testosterone and intratesticular testosterone levels were measured using a radioimmunoassay after 4 and 8 weeks of operation. Leydig cells were studied for apoptosis and expression of steroidogenetic acute regulatory （STAR） protein mRNA levels. Serum testosterone levels declined after 4 and 8 weeks of operation but were not significant （P〉0.05）. However, the intratesticular testosterone levels after 8 weeks were significantly decreased compared with the control group （P〈0.01）. The mean apoptosis index of Leydig cells in the experimental group was significantly higher than that in the control group after 4 or 8 weeks （P〈0.01）. StAR mRNA levels in the Leydig cells of the experimental group were significantly lower compared to those of the control group （P〈0.01）. Our data show that varicocele did impair Leydig cell function by increasing apoptosis and suppressing the expression of the StAR protein.展开更多
Aim： To evaluate the testosterone mimetic properties of icariin. Methods： Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each： the control g...Aim： To evaluate the testosterone mimetic properties of icariin. Methods： Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each： the control group （C）, the model group （M）, the icariin group （ICA） and the testosterone group （T）. The reproductive system was damaged by cyclophosphamide （intraperitoneal injection, 20 mg/kg·day） for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA （gastric gavage, 200 mg/kg·day） for the ICA group and sterandryl （subcutaneous injection, 5 rag/rat.day） for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, serum bone Gla-protein （BGP） and tartrate-resistant acid phosphatase activity in serum （StrACP） were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin （HE） staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling （TUNEL）, respectively. Results： （1） Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. （2） Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. （3） Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. Conclusion： Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.展开更多
Aim: To evaluate the key lesions in spermatogenesis suppressed partially by testosterone undecanoate (TU) treatment. Methods: Adult male SD rats were treated with vehicle or TU (19 mg/kg) injection (i.m.) every 15 day...Aim: To evaluate the key lesions in spermatogenesis suppressed partially by testosterone undecanoate (TU) treatment. Methods: Adult male SD rats were treated with vehicle or TU (19 mg/kg) injection (i.m.) every 15 days for 130 days. The numbers of all types of cells (nuclei) in the seminiferous tubules and the interstitial tissue were estimated using a contemporary stereological tool, the optical disector. Results: In response to TU treatment, the numbers of non-type B spermatogonia, type B spermatogonia and late elongated spermatids per testis were reduced to 51 %, 66 % and 14 % of the controls, respectively. The conversion ratios from type B spermatogonia to early spermatocytes and pachytene spermatocytes were not significantly affected and the ratios to the later germ cell types fell to 51 % - 65 % of the controls. Less than 1.0 % of immature round spermatids were seen sloughing into the tubule lumen, 4.0 % of elongated spermatids retained in the seminiferous epithelium, and about half of the elongated spermatid nuclei appreciably malformed. Leydig cells were atrophied but their number and the peritubular myoid cell number per testis were unchanged. Conclusion: Double inhibition of spermatogenesis (i.e. inhibition at spermiation and spermatogonial conversion to type B spermatogonia), a scenario seen in the monkey and human following gona-dotrophin withdrawal, was not sufficiently effective for a complete spermatogenic suppression in the rat after TU treatment, probably due to ineffective inhibition of the Leydig cell population and therefore the intra-testicular testosterone levels.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
Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although th...Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.展开更多
This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy （TRT） on hypogonadal men with type 2 diabetes mellitus （T2DM）. A literature search was performed using the Co...This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy （TRT） on hypogonadal men with type 2 diabetes mellitus （T2DM）. A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials （RCTs） were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration＇s Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels （mean difference （MD）. -1.10; 95% confidence interval （CI） （-1.88, -0.31））, fasting serum insulin levels （MD： -2.73; 95% CI （-3.62, -1.84））, HbAlc % （MD.. -0.87; 95% CI （-1.32, -0.42）） and triglyceride levels （MD： -0.35; 95% CI （-0.62, -0.07））. The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.展开更多
Despite regional variations in the prevalence of coronary artery disease （CAD）, men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are impl...Despite regional variations in the prevalence of coronary artery disease （CAD）, men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ＇Perspectives＇ article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ＇cause＇ versus ＇effect＇ controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease.展开更多
Testosterone supplementation therapy （TST） use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency ...Testosterone supplementation therapy （TST） use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency （TD）. Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.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Serum testosterone concentration levels were measured in 27 female patients with ovarian masses and n 8 female patients with malignant gastrointestinal tumors. The serum testasterone levels were found to be a more specific marker,compared with other methods, in the differential diagnosis of primary and metastatic tumors(P<0.01).Serum testosterone was at abnormally high levels inpatients with Krukenberg tumors assoiated with signet cells and luteinized stroma cells, but fell to very low levels after oophoiectomy. Testosterone levels were normal showever in patients with poorly-differentiated metastatic ovarisn tumors, or with gastro-intestinal cancers not involving the ovaries.We also found that testosaterone levels in patients with mucinous adenocarcinoma of either ovary or of the gastro-intestinal tract were higher than in patients with other types of tumor(P<0.05).
文摘背景:传统观察性研究难以揭露烧伤与生物标志物间的潜在因果关系,孟德尔随机化凭借遗传变异作为工具变量模拟随机对照试验的优势,成为解析复杂疾病因果关联的重要工具。目的:基于孟德尔随机化方法探讨烧伤与41种炎症因子和35种血液和尿液标志物的关系。方法:①烧伤的完整全基因组关联研究数据在IEU open gwas project数据库(由英国The University of Bristol构建)中获取,该数据包括了218131例样本,16380465个单核苷酸多态性;②41种炎症因子数据来源于芬兰青年心血管风险研究数据库(由图尔库大学应用和预防心血管医学研究中心构建)一项8293人的研究数据;③35种血液和尿液生物标志物数据来源于英国生物样本库(由英国政府、惠康基金会和英国医学研究理事会共同发起的大型生物医学数据库项目)(n=363228人)。以单核苷酸多态性作为工具变量,利用逆方差加权、MR Egger、加权中位数和加权模式的方法进行分析。采用Cochrane’s Q检验来识别结果的异质性,MR Egger截距检验和MR-PRESSO检验及“留一法”检验等评估暴露-结局关联的可靠性。结果与结论:烧伤降低了白细胞介素9(OR=0.97;95%CI,0.949 to 0.997;P=0.030)和睾酮(OR=0.997;95%CI,0.995 to 0.999;P=0.025)水平,且不存在异质性和水平多效性,证明了结果的稳健性。研究通过孟德尔随机化分析表明,烧伤后白细胞介素9和睾酮水平降低,提示提高白细胞介素9和睾酮水平可能有助于烧伤后组织修复和改善蛋白质分解速率。
文摘With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular （HPT） axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.
文摘To investigate the effect of arsenic on spermatogenesis. Methods: Mature (4 months old) Wistar rats were intraperitoneally administered sodium arsenite at doses of 4, 5 or 6 mg-kg^-day1 for 26 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), lutuneizing hormone (LH), testosterone and assessment of the epididymal sperm count. Results: In the 5 and 6 mg/kg groups, there were significant dose-dependent decreases in the accessory sex organ weights, epididymal sperm count and plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII. The changes were insignificant in the 4 mg/kg group. Conclusion: Arsenite has a suppressive influence on spermatogenesis and gonadotrophin and testosterone release in rats.
文摘Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone （LH） secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin （SHBG）, or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea （OSA） appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure （CPAP） does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture.
基金This work was supported by the National Natural Science Foundation of China （No. 81302223） and the Medical Scientific Research Foundation of Guangdong Province, China （B2013104）.
文摘Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day （n = 10 mice per dose）. Control animals （n = 10） received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein （STAR）, cytochrome P450 cholesterol side-chain cleavage enzyme （P450scc）, and 3β-hydroxysteroid dehydrogenase （3βHSD） in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone （ITT） concentration also increased in the VAP-treated groups. The expression of STAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis （STAR, P450scc, and 3β-HSD） and the following promotion of testosterone syothesis in vivo.
基金Acknowledgment This study was support by Natural Science Foundation of Shanghai, China （No. 06ZR14137）.
文摘Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.
文摘The aim of this study was to explore the effects of varicocele on the morphology and function of Leydig cells in the rat testis. Forty male Sprague-Dawley rats were divided into two groups： the experimental group underwent surgery to create a left varicocele （VC）, and the control group underwent a sham operation. Serum testosterone and intratesticular testosterone levels were measured using a radioimmunoassay after 4 and 8 weeks of operation. Leydig cells were studied for apoptosis and expression of steroidogenetic acute regulatory （STAR） protein mRNA levels. Serum testosterone levels declined after 4 and 8 weeks of operation but were not significant （P〉0.05）. However, the intratesticular testosterone levels after 8 weeks were significantly decreased compared with the control group （P〈0.01）. The mean apoptosis index of Leydig cells in the experimental group was significantly higher than that in the control group after 4 or 8 weeks （P〈0.01）. StAR mRNA levels in the Leydig cells of the experimental group were significantly lower compared to those of the control group （P〈0.01）. Our data show that varicocele did impair Leydig cell function by increasing apoptosis and suppressing the expression of the StAR protein.
文摘Aim： To evaluate the testosterone mimetic properties of icariin. Methods： Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each： the control group （C）, the model group （M）, the icariin group （ICA） and the testosterone group （T）. The reproductive system was damaged by cyclophosphamide （intraperitoneal injection, 20 mg/kg·day） for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA （gastric gavage, 200 mg/kg·day） for the ICA group and sterandryl （subcutaneous injection, 5 rag/rat.day） for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, serum bone Gla-protein （BGP） and tartrate-resistant acid phosphatase activity in serum （StrACP） were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin （HE） staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling （TUNEL）, respectively. Results： （1） Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. （2） Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. （3） Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. Conclusion： Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.
文摘Aim: To evaluate the key lesions in spermatogenesis suppressed partially by testosterone undecanoate (TU) treatment. Methods: Adult male SD rats were treated with vehicle or TU (19 mg/kg) injection (i.m.) every 15 days for 130 days. The numbers of all types of cells (nuclei) in the seminiferous tubules and the interstitial tissue were estimated using a contemporary stereological tool, the optical disector. Results: In response to TU treatment, the numbers of non-type B spermatogonia, type B spermatogonia and late elongated spermatids per testis were reduced to 51 %, 66 % and 14 % of the controls, respectively. The conversion ratios from type B spermatogonia to early spermatocytes and pachytene spermatocytes were not significantly affected and the ratios to the later germ cell types fell to 51 % - 65 % of the controls. Less than 1.0 % of immature round spermatids were seen sloughing into the tubule lumen, 4.0 % of elongated spermatids retained in the seminiferous epithelium, and about half of the elongated spermatid nuclei appreciably malformed. Leydig cells were atrophied but their number and the peritubular myoid cell number per testis were unchanged. Conclusion: Double inhibition of spermatogenesis (i.e. inhibition at spermiation and spermatogonial conversion to type B spermatogonia), a scenario seen in the monkey and human following gona-dotrophin withdrawal, was not sufficiently effective for a complete spermatogenic suppression in the rat after TU treatment, probably due to ineffective inhibition of the Leydig cell population and therefore the intra-testicular testosterone levels.
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.
基金supported by the Natural Science Foundation of Inner Mongolia Autonomous Region of China,No.2017LH0301(to JXJ),2016MS08108(to ZJY)Science and Technology Planning Project of Inner Mongolia Autonomous Region of China,No.201602069(to ZJY)+1 种基金PhD Scientific Research Fund of Baotou Medical College of China,No.BSJJ201606(to JXJ)"Dengfeng Project" Scientific Research Fund of Baotou Medical College of China,No.BYJJ-DF 201703(to JXJ)
文摘Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.
文摘This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy （TRT） on hypogonadal men with type 2 diabetes mellitus （T2DM）. A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials （RCTs） were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration＇s Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels （mean difference （MD）. -1.10; 95% confidence interval （CI） （-1.88, -0.31））, fasting serum insulin levels （MD： -2.73; 95% CI （-3.62, -1.84））, HbAlc % （MD.. -0.87; 95% CI （-1.32, -0.42）） and triglyceride levels （MD： -0.35; 95% CI （-0.62, -0.07））. The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.
文摘Despite regional variations in the prevalence of coronary artery disease （CAD）, men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ＇Perspectives＇ article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ＇cause＇ versus ＇effect＇ controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease.
文摘Testosterone supplementation therapy （TST） use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency （TD）. Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.
