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
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
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
Neuromuscular electrical stimulation(NMES) and testosterone replacement therapy(TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury(SCI). H...Neuromuscular electrical stimulation(NMES) and testosterone replacement therapy(TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury(SCI). However both interventions might increase heterotopic ossification(HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMES resistance training(RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches(4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMES-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas(CSA) of thewhole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A(NMES-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B(TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMES-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of preexisting HO.展开更多
Objective:Benign prostatic hyperplasia(BPH)is one of the most common diseases found among elderly men.Even though multiple risk factors of BPH have been identified in the past,the risk factors which have a direct impa...Objective:Benign prostatic hyperplasia(BPH)is one of the most common diseases found among elderly men.Even though multiple risk factors of BPH have been identified in the past,the risk factors which have a direct impact on prostate volume have not been identified.In this study,we aim to determine the most significant contributing risk factors to prostate volume enlargement by analyzing possible associated risk factors previously studied.Methods:This is a quantitative study with an analytical observational design,performed using a retrospective cohort approach.Total sampling was performed on 83 patients who underwent transurethral resection of the prostate(TURP)in Sanglah General Hospital from January to February 2019.Bivariate analysis is performed to examine each variable's association with prostate volume followed by a multivariate analysis.All variables were reassessed with path analysis to measure the direct effects,indirect effects,and total effects on prostate volume.Results:Bivariate analysis shows that serum testosterone(R=0.208;p=0.059)and prostate-specific antigen(PSA)level(R=0.626;p=0.001)have a significant association with prostate volume.Multivariate analysis shows that serum PSA(B=1.4;p=0.001;95%confidence interval[95%CI]=1.039-1.770)and testosterone(B=0.024;p=0.005;95%CI=0.008-0.041)levels are significant among all the analyzed risk factors.There is a significant and strong effect of PSA to prostate volume(c=0.636;p=0.001)whereas testosterone has a significant albeit weak effect to prostate volume(c=0.246;p=0.009)based on the total effect of the path analysis.Conclusion:Serum testosterone and PSA levels are significantly associated with prostatic volume increase among BPH patients.展开更多
We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further inves...We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha(TNF-α).Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α.TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction.To study the cellular mechanism of testosterone’s action,nuclear factor-kappa B(NF-κB)translocation was confirmed by electrophoretic mobility shift assays.We found that after NF-κB was activated by TNF-α,TFPI protein levels declined significantly by 37.3%compared with controls(P<0.001),and the mRNA levels of TFPI also decreased greatly(P<0.001).A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group.NF-κB DNA-binding activity was significantly suppressed by testosterone(P<0.05).This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.展开更多
Hypogonadism is prevalent in older men and testosteronereplacement therapy(TRT) for older hypogonadal men is a promising therapy. However, a number of important clinical concerns over TRT safety remain unsolved due to...Hypogonadism is prevalent in older men and testosteronereplacement therapy(TRT) for older hypogonadal men is a promising therapy. However, a number of important clinical concerns over TRT safety remain unsolved due to a lack of large-scale randomized clinical trials directly comparing the health risks of untreated hypogonadism vs long-term use of TRT. Meta-analyses of clinical trials of TRT as of 2010 have identified three major adverse events resulting from TRT: polycythemia, an increase in prostate-related events, and a slight reduction in serum high-density lipoprotein cholesterol. There are other purported health risks but their incidence can be neither confirmed nor denied based on the small number of subjects that have been studied to date. Furthermore, subsequent literature is equivocal with regard to the safety and utility of TRT and this topic has been subject to contentious debate. Since January 2014, the United States Food and Drug Administration has released two official announcements regarding the safety of TRT and clinical monitoring the risks in TRT users. Additionally, the health risks related to the clinical presentation of low or declining testosterone levels not been resolved in the current literature. Because TRT is prescribed in the context of putative risks resulting from reduced testosterone levels, we reviewed the epidemiology and reported risks of low testosterone levels. We also highlight the current information about TRT utilization, the risks most often claimed to be associated with TRT, and current or emerging alternatives to TRT.展开更多
Objective:To evaluate the effects of testosterone(T)on the maintenance of corpus cavernosum(CC)structure and apoptosis.Methods:Animals were divided into three groups:sham operation group(n Z 8)underwent sham operation...Objective:To evaluate the effects of testosterone(T)on the maintenance of corpus cavernosum(CC)structure and apoptosis.Methods:Animals were divided into three groups:sham operation group(n Z 8)underwent sham operation;Orchiectomized(Orchiec)t oily vehicle group(n Z 8)underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection(i.m.)30 days after orchiectomy;and Orchiec t T group(n Z 8)underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m.30 days after the surgery.Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine.Blood samples and penile tissue were collected on euthanasia.展开更多
Objectives: to evaluate the effectiveness of a natural compound made of Ecklonia bicyclis Seaweed, Tribulus terrestris and water-soluble chitosan oligosaccharide, in the male sexual asthenia with mild or mild-moderate...Objectives: to evaluate the effectiveness of a natural compound made of Ecklonia bicyclis Seaweed, Tribulus terrestris and water-soluble chitosan oligosaccharide, in the male sexual asthenia with mild or mild-moderate erectile dysfunction and serum testosterone levels between 280 and 350 ng/dl. Materials and Methods: 84 male patients affected by reduced libido and serum testosterone levels at the lower limit of normal, were recruited. We have separated patients in three different age groups: group A (18 - 45 years), group B (45 - 59 years), group C (>60 years). All subjects answered the International index of erectile function questionnaire (IIEF-5) and underwent determination of serum total testosterone before and after 30 days of treatment. Results: Before treatment, the group A showed mean (± standard deviation) total testosterone 321.9 ± 19.2 ng/dl and mean IIEF-5 18.6 ± 1.97, in the group B it was 318.5 ± 18.1 ng/dl and 16.3 ± 2.66, and finally in the group C it was 305.4 ± 13.1 ng/dl and 14.2 ± 1.95 respectively. After treatment mean total testosterone and mean IIEF-5 were respectively: group A (448 ± 111.46 ng/dl and 21.84 ± 3.41);group B (453.8 ± 105.23 ng/dl and 20.4 ± 3.81);group C (385.8 ± 87.29 ng/dl and 16.7 ± 3.84). Conclusions: The treatment with Ecklonia bicyclis, Tribulus terrestris and water-soluble chitosan oligosaccharide might represent a safe and effective option on the improvement of libido and erectile function in man with testosterone level at the lower limit of normal.展开更多
Autism spectrum disorder (ASD) is a neurodevelopmental disorder of unknown etiology. Social deficits represent one of the core symptoms of the diagnosis. The aim was to reveal possible correlations among peripheral le...Autism spectrum disorder (ASD) is a neurodevelopmental disorder of unknown etiology. Social deficits represent one of the core symptoms of the diagnosis. The aim was to reveal possible correlations among peripheral levels of oxytocin and testosterone with behavioral and symptom characteristics in patients with ASD. 8 children with ASD were recruited and underwent psychological profiling. Blood oxytocin and testosterone levels were analyzed using ELISA method. Oxytocin levels positively correlated with Adaptation to change category of CARS-2 (P = 0.008, R = 0.848) and Vineland-II maladaptive behavior scores (P = 0.004, R = 0.884). No significant correlations were found among testosterone levels and behavioral parameters. Higher oxytocin levels were connected with more severe adaptive behavior in ASD patients. Increased oxytocin levels in children with more severe phenotype could be a result of compensatory mechanism of impaired oxytocin signaling. Oxytocin seems to employ distinct mechanisms in regulating social behavior in autism and healthy population.展开更多
Background: Cellphone radiation (CR) has been reported to be related to higher risk of many health problems, but if CR can impair sexual behavior and testosterone synthesis has seldom been studied. Objective: To evalu...Background: Cellphone radiation (CR) has been reported to be related to higher risk of many health problems, but if CR can impair sexual behavior and testosterone synthesis has seldom been studied. Objective: To evaluate the effects of CR on testosterone and luteinizing hormone (LH) levels and sexual behaviors of male mice. Methods: Forty 3-month-old male mice, 22 - 25 g, were randomly allocated into four equal groups (n = 10 per group): the control group and three CR exposure groups including 8-hour group, 16-hour group and 24-hour group. Each mouse received different dose of CR exposure for 30 consecutive days. Sexual behaviors and testosterone and LH levels in serum were measured at the end of experiment. Furthermore, we also observed the weights of reproductive organs of each group, including testis, epididymis and seminal vesicle. Results: The mount latency and intromission latency in 24-hour group were significant higher than the control (both P < 0.01), while no obvious changes were seen in 8-hour group and 16-hour group (all P > 0.05). No difference in ejaculation latency existed among each group after the experiment (all P > 0.05). The frequency of mount and intromission in 24-hour group was statistically significantly lower than that of the control group (P < 0.05 and P < 0.01, respectively). No obvious change in the frequency of mount and intromission of the 8-hour group and 16-hour group was seen (all P > 0.05). Only the copulatory efficacy in the 24-hour group was statistically lower than the control group (P < 0.05). The serum levels of testosterone and LH in the 24-hour group were obviously higher than the control group (testosterone level: P < 0.05;LH level: P < 0.01). No significant differences were seen among the other two experimental groups and the control group (all P > 0.05). After the exposure of CR, the changes in the weights of sexual organs in the 24-hour group were significant compared with the control (testis weights, relative testis weight, epididymis weight, the weight of seminal vesicle, and the relative weight of seminal vesicle, all P < 0.01;the relative epididymis weight, P < 0.05). Conclusions: High dose exposure of CR can decline the testosterone and LH levels in mice and inhibit their sexual behaviors.展开更多
Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been report...Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.展开更多
In the present paper, changes of plasma testosterone and estradiol contents after moxibustion were analyzed in the old subjects. Results show that plasma testosterone of the old male subjects and estradiol content of ...In the present paper, changes of plasma testosterone and estradiol contents after moxibustion were analyzed in the old subjects. Results show that plasma testosterone of the old male subjects and estradiol content of the old male and female subjects rise following moxibustion. It indicatesthat moxibustion can regulate the functional state of the hypothalam us-hypophysis- sexual glang axis,improve neuroendocrine disorder, prevent the sexual glang from atrophy and delay senility. Increase ofthe two hormones in the human body can lead to a series of regulations in other respects. Therefore,moxibustion is of an important role in delaying senility.展开更多
Objective: To investigate the effects of acute and chronic aqueous garlic extract ingestion on testicular cellular integrity and serum testosterone levels.Methods: Twenty(20) male Sprague-Dawley rats weighing an avera...Objective: To investigate the effects of acute and chronic aqueous garlic extract ingestion on testicular cellular integrity and serum testosterone levels.Methods: Twenty(20) male Sprague-Dawley rats weighing an average of 120 g were used.Animals were divided into three groups. Group A served as control(10 rats for 28 and 56 d respectively), while treatment Groups B and C were given 200 mg/kg for Allium sativum(garlic cloves) extract for 28 and 56 d respectively.Results: Histological analysis revealed the presence of all spermatogenic lineages, appearance of proliferative activities in the interstitial cells, as well as increased serum testosterone levels.Conclusions: This study confirmed proliferative and restorative potentials in both acute and chronic garlic ingestion.展开更多
The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group wer...The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detec-tion (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly re-duced norepinephrine release (P<0.01),and the norepinepherine overflow was similar between the con-trol and 0.1 nmol/L testosterone group (P>0.05).Electrical stimulation of the ventricle evoked norepi-nepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P<0.01).It is suggested that testosterone suppresses ischemia-and electri-cal stimulationinduced norepinepherine release in the isolated rat hearts.展开更多
AIM: To investigate the time course of testosterone(T) recovery after cessation of androgen deprivation therapy(ADT) in patients treated with brachytherapy. METHODS: One-hundred and seventy-four patients treated betwe...AIM: To investigate the time course of testosterone(T) recovery after cessation of androgen deprivation therapy(ADT) in patients treated with brachytherapy. METHODS: One-hundred and seventy-four patients treated between June 1999 and February 2009 were studied. Patients were divided into a short-term usage group(≤ 12 mo, n = 91) and a long-term usage group(≥ 36 mo, n = 83) according to the duration of gonadotropin-releasing hormone agonist therapy. Median follow-up was 29 mo in the short-term group and was 60 mo in the long-term group.RESULTS: Cumulative incidence rates of T recovery to normal and supracastrate levels at 24 mo after cessationwere 28.8% and 74.6%, respectively, in the long-term usage group, whereas these values were 96.4% and 98.8% in the short-term usage group. T recovery to normal and supracastrate levels occurred significantly more rapidly in the short-term than in the long-term usage group(P < 0.001 and P < 0.001, respectively). Five years after cessation, 22.6% of patients maintained a castrate T level in the long-term usage group. On multivariate analysis, lower T levels(< 10 ng/d L) at cessation of ADT was significantly associated with prolonged T recovery to supracastrate levels in the longterm usage group(P = 0.002). CONCLUSION: Lower T levels at cessation of ADT were associated with prolonged T recovery in the longterm usage group. Five years after cessation of longterm ADT, approximately one-fifth of patients still had castrate T levels. When determining the therapeutic effect, especially biochemical control, we should consider this delay in T recovery.展开更多
BACKGROUND Testosterone level of < 50 ng/dL has been used to define castrate level after surgery or after androgen deprivation treatment (ADT) in metastatic prostate cancer (PC). AIM To evaluate the effect of two d...BACKGROUND Testosterone level of < 50 ng/dL has been used to define castrate level after surgery or after androgen deprivation treatment (ADT) in metastatic prostate cancer (PC). AIM To evaluate the effect of two different castrate testosterone levels,< 50 and < 20 ng/dL, on biochemical relapse free survival (BRFS) in patients with nonmetastatic intermediate and high risk PC receiving definitive radiotherapy (RT) and ADT. METHODS Between April 1998 and February 2011;173 patients with intermediate and high risk disease were treated. Radiotherapy was delivered by either threedimensional- conformal technique to a total dose of 73.4 Gy at the ICRU reference point or intensity modulated radiotherapy technique to a total dose of 76 Gy. All the patients received 3 mo of neoadjuvant ADT followed by RT and additional 6 mo of ADT. ASTRO Phoenix definition was used to define biochemical relapse. RESULTS Median follow up duration was 125 months. Ninety-six patients (56%) had castrate testosterone level < 20 ng/dL and 139 patients (80%) had castrate testosterone level < 50 ng/dL. Both values are valid at predicting BRFS. However, patients with testosterone < 20 ng/dL have significantly better BRFS compared to other groups (P = 0.003). When we compare two values, it was found that using 20 ng/dL is better than 50 ng/dL in predicting the BRFS (AUC = 0.63 vs 0.58, respectively). CONCLUSION Castrate testosterone level of less than 20 ng/dL is associated with better BRFS and is better in predicting the BRFS. Further studies using current standard of care of high dose IMRT and longer ADT duration might support these findings.展开更多
Elemental sulfur has been used as a traditional Chinese medicine to treat the late-onset hypogonadism and impotence without a clarified mechanism for many hundreds of years.In the present study,mice were received sulf...Elemental sulfur has been used as a traditional Chinese medicine to treat the late-onset hypogonadism and impotence without a clarified mechanism for many hundreds of years.In the present study,mice were received sulfur or distilled water for 35 days by daily intragastric gavage at a dose of 250 mg/kg body weight.Then,the serum testosterone level and genes associated with testicular testosterone biosynthesis(TTB)were detected.The gut microbiota was also analyzed by 16S rRNA gene sequencing.Serum testosterone level was significantly increased by 291.1%in sulfur-treated mice.The H2S levels in serum and feces were significantly increased.The expression of genes associated with TTB including StAR,p450c17,3β-HSD,and P450scc in testes were significantly upregulated by Sulfur and NaHS,suggesting that sulfur promotes TTB depending on H2S.In addition,sulfur increased the diversity of gut microbiota and the abundance of several bacteria associated with sulfur metabolism,including genus Prevotella,which might be positively associated with serum level of testosterone in boys.Five pathways including bile secretion,carotenoid biosynthesis,lipid biosynthesis proteins,propanoate metabolism,and biosynthesis of type II polyketide products,were identified to associate with sulfur.Together,our results suggested that sulfur upregulated testicular testosterone biosynthesis via H2S,which was associated with alteration of gut microbiota in mice.Our study highlights a mechanism for the treatment of late-onset hypogonadism and impotence by sulfur.展开更多
Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity,sexual dysfunction,increase body fat,weight gain and the development of ca...Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity,sexual dysfunction,increase body fat,weight gain and the development of cardiac disease.Objective We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks factors.Methods Fifty-six self referred men without diabetes mellitus,hypertension,or cardiovascular disease(ages 52.3±7.8 years)were randomly selected from a large cohort.Baseline weight,body fat composition,fasting glucose,hemoglobin A1c and fasting lipid levels,as well as free and total testosterone levels were assessed.All patients were assessed and followed 6–18 months after initiation of the program.The program consisted of a low glycemic load balanced nutrition diet,a recommended structured daily exercise program of 30–60 minutes,as well as once to twice weekly intramuscular testosterone injections(113.0±27.8 mg).Results At follow up,weight was reduced from 233.9±30.0 pounds(lbs)to 221.3±25.1 lbs(P<0.001),BMI was reduced from 33.2±3.3 kg/m2 to 31.3±2.8 kg/m^(2)(P<0.0001).Total body fat was 27.1%±5.2%vs.34.3%±5.7%at baseline(P<0.0001).Fasting glucose was reduced from 95.3±14.4 mg/dL to 87.5±12.6 mg/dL(P<0.0001).Total cholesterol was reduced from 195.4±33.0 mg/dL to 172.7±35.0 mg/dL(P<0.005).No clinically significant adverse events were recorded.Conclusions Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was granted.The combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.展开更多
Heart failure(HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality. Testosterone is one of the most researched hormon...Heart failure(HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality. Testosterone is one of the most researched hormones in the course of HF. Growing interest regarding the effect of testosterone, on a variety of body systems, has increased the knowledge about its mechanisms of action. The terms central and peripheral effects are used to distinguish the effects of testosterone on cardiac and extracardiac structures. Central effects include influences on cardiomyocytes and electrophysiology. Peripheral effects include influences on blood vessels, baroreceptor reactivity, skeletal muscles and erythropoesis. Current knowledge about peripheral effects of testosterone may explain much about beneficiary effects in the pathophysiology of HF syndrome. However, central, i.e., cardiac effects of testosterone are to be further explored.展开更多
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.
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Neuromuscular electrical stimulation(NMES) and testosterone replacement therapy(TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury(SCI). However both interventions might increase heterotopic ossification(HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMES resistance training(RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches(4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMES-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas(CSA) of thewhole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A(NMES-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B(TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMES-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of preexisting HO.
文摘Objective:Benign prostatic hyperplasia(BPH)is one of the most common diseases found among elderly men.Even though multiple risk factors of BPH have been identified in the past,the risk factors which have a direct impact on prostate volume have not been identified.In this study,we aim to determine the most significant contributing risk factors to prostate volume enlargement by analyzing possible associated risk factors previously studied.Methods:This is a quantitative study with an analytical observational design,performed using a retrospective cohort approach.Total sampling was performed on 83 patients who underwent transurethral resection of the prostate(TURP)in Sanglah General Hospital from January to February 2019.Bivariate analysis is performed to examine each variable's association with prostate volume followed by a multivariate analysis.All variables were reassessed with path analysis to measure the direct effects,indirect effects,and total effects on prostate volume.Results:Bivariate analysis shows that serum testosterone(R=0.208;p=0.059)and prostate-specific antigen(PSA)level(R=0.626;p=0.001)have a significant association with prostate volume.Multivariate analysis shows that serum PSA(B=1.4;p=0.001;95%confidence interval[95%CI]=1.039-1.770)and testosterone(B=0.024;p=0.005;95%CI=0.008-0.041)levels are significant among all the analyzed risk factors.There is a significant and strong effect of PSA to prostate volume(c=0.636;p=0.001)whereas testosterone has a significant albeit weak effect to prostate volume(c=0.246;p=0.009)based on the total effect of the path analysis.Conclusion:Serum testosterone and PSA levels are significantly associated with prostatic volume increase among BPH patients.
基金the National Natural Science Foundation of China(No.30670842)the Natural Science Foundation of Guangdong Province,China(No.5300582).
文摘We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha(TNF-α).Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α.TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction.To study the cellular mechanism of testosterone’s action,nuclear factor-kappa B(NF-κB)translocation was confirmed by electrophoretic mobility shift assays.We found that after NF-κB was activated by TNF-α,TFPI protein levels declined significantly by 37.3%compared with controls(P<0.001),and the mRNA levels of TFPI also decreased greatly(P<0.001).A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group.NF-κB DNA-binding activity was significantly suppressed by testosterone(P<0.05).This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.
文摘Hypogonadism is prevalent in older men and testosteronereplacement therapy(TRT) for older hypogonadal men is a promising therapy. However, a number of important clinical concerns over TRT safety remain unsolved due to a lack of large-scale randomized clinical trials directly comparing the health risks of untreated hypogonadism vs long-term use of TRT. Meta-analyses of clinical trials of TRT as of 2010 have identified three major adverse events resulting from TRT: polycythemia, an increase in prostate-related events, and a slight reduction in serum high-density lipoprotein cholesterol. There are other purported health risks but their incidence can be neither confirmed nor denied based on the small number of subjects that have been studied to date. Furthermore, subsequent literature is equivocal with regard to the safety and utility of TRT and this topic has been subject to contentious debate. Since January 2014, the United States Food and Drug Administration has released two official announcements regarding the safety of TRT and clinical monitoring the risks in TRT users. Additionally, the health risks related to the clinical presentation of low or declining testosterone levels not been resolved in the current literature. Because TRT is prescribed in the context of putative risks resulting from reduced testosterone levels, we reviewed the epidemiology and reported risks of low testosterone levels. We also highlight the current information about TRT utilization, the risks most often claimed to be associated with TRT, and current or emerging alternatives to TRT.
基金We thank Urogenital Research Unit staff,UERJ,for technical support and UFCSPA,CNPq(MCT/CNPq 15/2007),Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nıvel Superior e CAPES and FAPERGS(11/1003-5 e 02/2011)for financial support.
文摘Objective:To evaluate the effects of testosterone(T)on the maintenance of corpus cavernosum(CC)structure and apoptosis.Methods:Animals were divided into three groups:sham operation group(n Z 8)underwent sham operation;Orchiectomized(Orchiec)t oily vehicle group(n Z 8)underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection(i.m.)30 days after orchiectomy;and Orchiec t T group(n Z 8)underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m.30 days after the surgery.Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine.Blood samples and penile tissue were collected on euthanasia.
文摘Objectives: to evaluate the effectiveness of a natural compound made of Ecklonia bicyclis Seaweed, Tribulus terrestris and water-soluble chitosan oligosaccharide, in the male sexual asthenia with mild or mild-moderate erectile dysfunction and serum testosterone levels between 280 and 350 ng/dl. Materials and Methods: 84 male patients affected by reduced libido and serum testosterone levels at the lower limit of normal, were recruited. We have separated patients in three different age groups: group A (18 - 45 years), group B (45 - 59 years), group C (>60 years). All subjects answered the International index of erectile function questionnaire (IIEF-5) and underwent determination of serum total testosterone before and after 30 days of treatment. Results: Before treatment, the group A showed mean (± standard deviation) total testosterone 321.9 ± 19.2 ng/dl and mean IIEF-5 18.6 ± 1.97, in the group B it was 318.5 ± 18.1 ng/dl and 16.3 ± 2.66, and finally in the group C it was 305.4 ± 13.1 ng/dl and 14.2 ± 1.95 respectively. After treatment mean total testosterone and mean IIEF-5 were respectively: group A (448 ± 111.46 ng/dl and 21.84 ± 3.41);group B (453.8 ± 105.23 ng/dl and 20.4 ± 3.81);group C (385.8 ± 87.29 ng/dl and 16.7 ± 3.84). Conclusions: The treatment with Ecklonia bicyclis, Tribulus terrestris and water-soluble chitosan oligosaccharide might represent a safe and effective option on the improvement of libido and erectile function in man with testosterone level at the lower limit of normal.
文摘Autism spectrum disorder (ASD) is a neurodevelopmental disorder of unknown etiology. Social deficits represent one of the core symptoms of the diagnosis. The aim was to reveal possible correlations among peripheral levels of oxytocin and testosterone with behavioral and symptom characteristics in patients with ASD. 8 children with ASD were recruited and underwent psychological profiling. Blood oxytocin and testosterone levels were analyzed using ELISA method. Oxytocin levels positively correlated with Adaptation to change category of CARS-2 (P = 0.008, R = 0.848) and Vineland-II maladaptive behavior scores (P = 0.004, R = 0.884). No significant correlations were found among testosterone levels and behavioral parameters. Higher oxytocin levels were connected with more severe adaptive behavior in ASD patients. Increased oxytocin levels in children with more severe phenotype could be a result of compensatory mechanism of impaired oxytocin signaling. Oxytocin seems to employ distinct mechanisms in regulating social behavior in autism and healthy population.
文摘Background: Cellphone radiation (CR) has been reported to be related to higher risk of many health problems, but if CR can impair sexual behavior and testosterone synthesis has seldom been studied. Objective: To evaluate the effects of CR on testosterone and luteinizing hormone (LH) levels and sexual behaviors of male mice. Methods: Forty 3-month-old male mice, 22 - 25 g, were randomly allocated into four equal groups (n = 10 per group): the control group and three CR exposure groups including 8-hour group, 16-hour group and 24-hour group. Each mouse received different dose of CR exposure for 30 consecutive days. Sexual behaviors and testosterone and LH levels in serum were measured at the end of experiment. Furthermore, we also observed the weights of reproductive organs of each group, including testis, epididymis and seminal vesicle. Results: The mount latency and intromission latency in 24-hour group were significant higher than the control (both P < 0.01), while no obvious changes were seen in 8-hour group and 16-hour group (all P > 0.05). No difference in ejaculation latency existed among each group after the experiment (all P > 0.05). The frequency of mount and intromission in 24-hour group was statistically significantly lower than that of the control group (P < 0.05 and P < 0.01, respectively). No obvious change in the frequency of mount and intromission of the 8-hour group and 16-hour group was seen (all P > 0.05). Only the copulatory efficacy in the 24-hour group was statistically lower than the control group (P < 0.05). The serum levels of testosterone and LH in the 24-hour group were obviously higher than the control group (testosterone level: P < 0.05;LH level: P < 0.01). No significant differences were seen among the other two experimental groups and the control group (all P > 0.05). After the exposure of CR, the changes in the weights of sexual organs in the 24-hour group were significant compared with the control (testis weights, relative testis weight, epididymis weight, the weight of seminal vesicle, and the relative weight of seminal vesicle, all P < 0.01;the relative epididymis weight, P < 0.05). Conclusions: High dose exposure of CR can decline the testosterone and LH levels in mice and inhibit their sexual behaviors.
基金supported in part by funds obtained through an Italian law that allows taxpayers to allocate 0.5 percent share of their income tax contribution to a research institution of their choice
文摘Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.
文摘In the present paper, changes of plasma testosterone and estradiol contents after moxibustion were analyzed in the old subjects. Results show that plasma testosterone of the old male subjects and estradiol content of the old male and female subjects rise following moxibustion. It indicatesthat moxibustion can regulate the functional state of the hypothalam us-hypophysis- sexual glang axis,improve neuroendocrine disorder, prevent the sexual glang from atrophy and delay senility. Increase ofthe two hormones in the human body can lead to a series of regulations in other respects. Therefore,moxibustion is of an important role in delaying senility.
文摘Objective: To investigate the effects of acute and chronic aqueous garlic extract ingestion on testicular cellular integrity and serum testosterone levels.Methods: Twenty(20) male Sprague-Dawley rats weighing an average of 120 g were used.Animals were divided into three groups. Group A served as control(10 rats for 28 and 56 d respectively), while treatment Groups B and C were given 200 mg/kg for Allium sativum(garlic cloves) extract for 28 and 56 d respectively.Results: Histological analysis revealed the presence of all spermatogenic lineages, appearance of proliferative activities in the interstitial cells, as well as increased serum testosterone levels.Conclusions: This study confirmed proliferative and restorative potentials in both acute and chronic garlic ingestion.
基金supported by grants from the National Natural Science Foundation of China (No. 30670880)the Shanghai Municipal Natural Science Foundation (No. XD1402600)
文摘The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detec-tion (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly re-duced norepinephrine release (P<0.01),and the norepinepherine overflow was similar between the con-trol and 0.1 nmol/L testosterone group (P>0.05).Electrical stimulation of the ventricle evoked norepi-nepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P<0.01).It is suggested that testosterone suppresses ischemia-and electri-cal stimulationinduced norepinepherine release in the isolated rat hearts.
文摘AIM: To investigate the time course of testosterone(T) recovery after cessation of androgen deprivation therapy(ADT) in patients treated with brachytherapy. METHODS: One-hundred and seventy-four patients treated between June 1999 and February 2009 were studied. Patients were divided into a short-term usage group(≤ 12 mo, n = 91) and a long-term usage group(≥ 36 mo, n = 83) according to the duration of gonadotropin-releasing hormone agonist therapy. Median follow-up was 29 mo in the short-term group and was 60 mo in the long-term group.RESULTS: Cumulative incidence rates of T recovery to normal and supracastrate levels at 24 mo after cessationwere 28.8% and 74.6%, respectively, in the long-term usage group, whereas these values were 96.4% and 98.8% in the short-term usage group. T recovery to normal and supracastrate levels occurred significantly more rapidly in the short-term than in the long-term usage group(P < 0.001 and P < 0.001, respectively). Five years after cessation, 22.6% of patients maintained a castrate T level in the long-term usage group. On multivariate analysis, lower T levels(< 10 ng/d L) at cessation of ADT was significantly associated with prolonged T recovery to supracastrate levels in the longterm usage group(P = 0.002). CONCLUSION: Lower T levels at cessation of ADT were associated with prolonged T recovery in the longterm usage group. Five years after cessation of longterm ADT, approximately one-fifth of patients still had castrate T levels. When determining the therapeutic effect, especially biochemical control, we should consider this delay in T recovery.
文摘BACKGROUND Testosterone level of < 50 ng/dL has been used to define castrate level after surgery or after androgen deprivation treatment (ADT) in metastatic prostate cancer (PC). AIM To evaluate the effect of two different castrate testosterone levels,< 50 and < 20 ng/dL, on biochemical relapse free survival (BRFS) in patients with nonmetastatic intermediate and high risk PC receiving definitive radiotherapy (RT) and ADT. METHODS Between April 1998 and February 2011;173 patients with intermediate and high risk disease were treated. Radiotherapy was delivered by either threedimensional- conformal technique to a total dose of 73.4 Gy at the ICRU reference point or intensity modulated radiotherapy technique to a total dose of 76 Gy. All the patients received 3 mo of neoadjuvant ADT followed by RT and additional 6 mo of ADT. ASTRO Phoenix definition was used to define biochemical relapse. RESULTS Median follow up duration was 125 months. Ninety-six patients (56%) had castrate testosterone level < 20 ng/dL and 139 patients (80%) had castrate testosterone level < 50 ng/dL. Both values are valid at predicting BRFS. However, patients with testosterone < 20 ng/dL have significantly better BRFS compared to other groups (P = 0.003). When we compare two values, it was found that using 20 ng/dL is better than 50 ng/dL in predicting the BRFS (AUC = 0.63 vs 0.58, respectively). CONCLUSION Castrate testosterone level of less than 20 ng/dL is associated with better BRFS and is better in predicting the BRFS. Further studies using current standard of care of high dose IMRT and longer ADT duration might support these findings.
基金the National Natural Science Foundation of China(grant numbers 81571495,81971443)Innovation-Oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation(CX2017-7)Science and Technology Climbing Fund of SIPPR(PD2017-3).
文摘Elemental sulfur has been used as a traditional Chinese medicine to treat the late-onset hypogonadism and impotence without a clarified mechanism for many hundreds of years.In the present study,mice were received sulfur or distilled water for 35 days by daily intragastric gavage at a dose of 250 mg/kg body weight.Then,the serum testosterone level and genes associated with testicular testosterone biosynthesis(TTB)were detected.The gut microbiota was also analyzed by 16S rRNA gene sequencing.Serum testosterone level was significantly increased by 291.1%in sulfur-treated mice.The H2S levels in serum and feces were significantly increased.The expression of genes associated with TTB including StAR,p450c17,3β-HSD,and P450scc in testes were significantly upregulated by Sulfur and NaHS,suggesting that sulfur promotes TTB depending on H2S.In addition,sulfur increased the diversity of gut microbiota and the abundance of several bacteria associated with sulfur metabolism,including genus Prevotella,which might be positively associated with serum level of testosterone in boys.Five pathways including bile secretion,carotenoid biosynthesis,lipid biosynthesis proteins,propanoate metabolism,and biosynthesis of type II polyketide products,were identified to associate with sulfur.Together,our results suggested that sulfur upregulated testicular testosterone biosynthesis via H2S,which was associated with alteration of gut microbiota in mice.Our study highlights a mechanism for the treatment of late-onset hypogonadism and impotence by sulfur.
基金supported by the Cenegenics Education and Research Foundation,a non-profit entity.
文摘Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity,sexual dysfunction,increase body fat,weight gain and the development of cardiac disease.Objective We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks factors.Methods Fifty-six self referred men without diabetes mellitus,hypertension,or cardiovascular disease(ages 52.3±7.8 years)were randomly selected from a large cohort.Baseline weight,body fat composition,fasting glucose,hemoglobin A1c and fasting lipid levels,as well as free and total testosterone levels were assessed.All patients were assessed and followed 6–18 months after initiation of the program.The program consisted of a low glycemic load balanced nutrition diet,a recommended structured daily exercise program of 30–60 minutes,as well as once to twice weekly intramuscular testosterone injections(113.0±27.8 mg).Results At follow up,weight was reduced from 233.9±30.0 pounds(lbs)to 221.3±25.1 lbs(P<0.001),BMI was reduced from 33.2±3.3 kg/m2 to 31.3±2.8 kg/m^(2)(P<0.0001).Total body fat was 27.1%±5.2%vs.34.3%±5.7%at baseline(P<0.0001).Fasting glucose was reduced from 95.3±14.4 mg/dL to 87.5±12.6 mg/dL(P<0.0001).Total cholesterol was reduced from 195.4±33.0 mg/dL to 172.7±35.0 mg/dL(P<0.005).No clinically significant adverse events were recorded.Conclusions Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was granted.The combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.
文摘Heart failure(HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality. Testosterone is one of the most researched hormones in the course of HF. Growing interest regarding the effect of testosterone, on a variety of body systems, has increased the knowledge about its mechanisms of action. The terms central and peripheral effects are used to distinguish the effects of testosterone on cardiac and extracardiac structures. Central effects include influences on cardiomyocytes and electrophysiology. Peripheral effects include influences on blood vessels, baroreceptor reactivity, skeletal muscles and erythropoesis. Current knowledge about peripheral effects of testosterone may explain much about beneficiary effects in the pathophysiology of HF syndrome. However, central, i.e., cardiac effects of testosterone are to be further explored.
