Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low ...Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.展开更多
This study sought to investigate late-onset hypogonadism (LOH) in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases ...This study sought to investigate late-onset hypogonadism (LOH) in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms (AMS) scale and androgen deficiency in aging males (ADAM) questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors (total testosterone (TT), free testosterone (fT), sex hormone-binding globulin (SHBG) and bioavailability of testosterone (Bio-T)). There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results: TT was not related to aging (P〉O.05); levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.展开更多
Although testosterone replacement therapy(TRT)is the first-choice method used worldwide for late-onset hypogonadism(LOH),clinical benefits are not seen in all cases.This study was conducted to determine the predictors...Although testosterone replacement therapy(TRT)is the first-choice method used worldwide for late-onset hypogonadism(LOH),clinical benefits are not seen in all cases.This study was conducted to determine the predictors of TRT efficacy for LOH.Fifty-six patients who visited our Men’s Health Clinic(Kawanishi City Medical Center,Kawanishi and Hyogo Medical University,Nishinomiya,Hyogo,Japan)between November 2003 and June 2021 with data available before and after TRT were enrolled.They were divided into responders(Group 1;n=45,accounting for 80.4%)and nonresponders(Group 2;n=11,accounting for 19.6%)based on the clinical response to TRT,including patient satisfaction.Factors noted before TRT included age,body mass index,aging males’symptoms score,sexual health inventory for men,luteinizing hormone,follicular-stimulating hormone,testosterone,free testosterone,prolactin(PRL),estradiol(E2),and testosterone/estradiol(T/E2)ratio in serum.For statistical analysis,a multivariable logistic regression model was used.Univariate analysis revealed PRL(odds ratio TORI:0.9624;95%confidence interval[Cl]:0.9316-0.9943,P<0.05),E2(OR:0.8692;95%Cl:0.7745-0.9754,P<0.05),and T/E2 ratio(OR:1.1312;95%Cl:1.0106-1.2661,P<0.05)to be predictive factors.Multivariate analyses showed that T/E2 ratio was an independent predictive factor(OR:1.1593;95%Cl:1.0438-1.2875,P<0.01).The present results suggest that a low value for T/E2 ratio may predict a reduced response to TRT.The T/E2 ratio threshold to predict nonresponders based on receiver-operating characteristics(ROC)curve analysis was shown to be 17.3.Although additional studies with larger number of patients are necessary,we propose the determination of serum E2 level and testosterone level prior to performing TRT.展开更多
Introduction: Studies showed a high prevalence of metabolic abnormalities including dyslipidemia, type 2 diabetes in cases of low testosterone in men and which are associated with increased cardiovascular risk. Hypogo...Introduction: Studies showed a high prevalence of metabolic abnormalities including dyslipidemia, type 2 diabetes in cases of low testosterone in men and which are associated with increased cardiovascular risk. Hypogonadism represents the second cause of endocrine osteoporosis. Objectives: The objectives of our work were: to determine the main causes of hypogonadism in women and men;to assess the frequency of metabolic and osteosdensitometric abnormalities in the hypogonadal population. Patients and methods: A retrospective descriptive study was carried out over 7 years on 120 patients, hospitalized in the Endocrinology department of the Hassan II University Hospital of Fez-Morocco for hypogonadism. The patients selected were those who had symptoms of hypogonadism confirmed in men by: low total testosterone for Tanner stage in adolescents, ng/ml or lower limit of normal for adults;in women, hypoestrogenia 30 pg/l. Gonadotropin dosage, karyotype, pelvic or testicular ultrasound and pituitary MRI, for etiological diagnosis, were performed. Bone densitometry was performed for bone impact and lipid profile for metabolic profile. Results: Out of 120 patients, there were 77 women and 43 men. The average age was 31.51 years. In men, the main causes were central hypogonadism in 67.4% and primary testicular failure in 32.6%. In women, central hypogonadism was also the most common cause noted in 63.7% and premature ovarian failure was observed in 36.4%. HypoHDL was significantly more frequent p (0.005) in women, osteopenia and osteoporosis were significantly more frequent in women than in men p (0.046). Conclusion: Central causes represent the most common etiology of hypogonadism in both sexes;abnormalities of bone mineralization and metabolic disorders were predominant in women.展开更多
Gordon Holmes Syndrome is a rare inherited disease characterized by both neurological and reproductive signs and symptoms. Most patients develop neurologic challenges in early adulthood and cerebellar ataxia occurs as...Gordon Holmes Syndrome is a rare inherited disease characterized by both neurological and reproductive signs and symptoms. Most patients develop neurologic challenges in early adulthood and cerebellar ataxia occurs as the disease progresses. In the majority of patients, hypogonadism is hypogonadotropic but rarely hypergonadotropic. We report a case of a 26-year-old female in Nigeria, with hypergonadotropic hypogonadism and cerebellar atrophy from a non-consanguineous marriage and no family history.展开更多
The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone therapy.We aim to provide an updated and prac...The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone therapy.We aim to provide an updated and practical approach towards its management.We did a comprehensive literature search across MEDLINE(via PubMed),Scopus,and Google Scholar databases using the keywords“MOSH”OR“Obesity-related hypogonadism”OR“Testosterone replacement therapy”OR“Selective estrogen receptor modulator”OR“SERM”OR“Guidelines on male hypogonadism”as well as a manual search of references within the articles.A narrative review based on available evidence,recommendations and their practical implications was done.Although weight loss is the ideal therapeutic strategy for patients with MOSH,achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice.Therefore,androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity.However,there is conflicting evidence for the appropriate use of testosterone replacement therapy(TRT),and it can also be associated with complications.This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH.Before starting testosterone replacement in functional hypogonadism of obesity,it would be desirable to initiate lifestyle modification to ensure weight reduction.TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients.Balancing the risks and benefits of TRT should be considered in every patient before and during longterm management.展开更多
Objective:Testosterone deficiency may be a risk factor for lower urinary tract symptoms(LUTS),and there may be a causal ink between the emergence of LUTS and the incidence of late-onset hypogonadism(LOH).We perfomed a...Objective:Testosterone deficiency may be a risk factor for lower urinary tract symptoms(LUTS),and there may be a causal ink between the emergence of LUTS and the incidence of late-onset hypogonadism(LOH).We perfomed an epidemiologic study to investigate the association between symptomatic late-onset hypogonadism(SLOH)and LUTS in middle-aged and elderly rural Chinese males.Methods:A total of 965 men completed a questionnaire and underwent a detailed physical examination.The Aging Males'Symptoms(AMS)scale was used to assess SLOH,and the International Prostate Symptom Score(IPSS)questionnaire was used to assess LUTS.Serum reproductive hormone levels of testosterone,sex hormone-binding globulin(SHBG)and luteinizing hormone(LH)were measured.Results:A total of 965 males(mean age:56.34±8.85,range:40-80 years)were recruited for the present study.A total of 20.93%(202/965)were diagnosed with SLOH.A total of 93.16%(899/965)had mild LUTS,5.18%(50/965)had moderate LUTS,and 1.66%(16/965)had severe LUTS.Among SLOH patients,13.40%(27/202)and 3.90%(8/202)had moderate and severe LUTS,respectively.Patients with severe LUTS had increased SHBG and LH compared with those with mild and moderate LUTS(P<0.01).Correlation analysis revealed that the AMS total score was positively correlated with the IPSS score(P<0.05).The prevalence of SLOH was significantly increased with LUTS severity In addition to the known effect of age,the results of mutiple regression analysis also showed that serum LH or SHBG appeared to have a weak link with SLOH and LUTS that requires etiological and biological clarification in our future study.Conclusion:In this cross-sectional analysis of SLOH and LUTS,LUTS severity was significantly associated with hypogonadism symptoms.Additionally,the prevalence of SLOH advanced with increasing LUTS severity.Serum SHBG or LH showed a positive correlation with SLOH and LUTS.展开更多
This study aimed to propose an operational definition of late-onset hypogonadism(LOH)that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in Chi...This study aimed to propose an operational definition of late-onset hypogonadism(LOH)that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China.A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China.Serum total testosterone(TT),sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were measured and free testosterone(cFT)was calculated.The Aging Males’Symptoms(AMS)scale was used to evaluate the LOH symptoms.Finally,5078 men were included in this analysis.The TT levels did not decrease with age(P=0.59),and had no relationship with AMS symptoms(P=0.87 for AMS total score,P=0.74 for≥3 sexual symptoms).The cFT levels decreased significantly with age(P<0.01)and showed a negative association with the presence of≥3 sexual symptoms(P=0.03).The overall estimated prevalence of LOH was 7.8%(395/5078)if a cFT level<210 pmol l−1 combined with the presence of≥3 sexual symptoms was used as the criterion of LOH.Among them,26.1%(103/395)and 73.9%(292/395)had primary and secondary hypogonadism,respectively.After adjustment for confounding factors,primary and secondary hypogonadism was positively related to age and comorbidities.Body mass index was an independent risk factor for secondary hypogonadism.The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone,and that the cFT level is more reliable than TT for LOH diagnosis.Secondary hypogonadism is the most common form of LOH.展开更多
Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active l...Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS), International Index of Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36) scale (P= 0.0318). ART was also associated with significant decreases in waist circumstance (P = 0.002) and serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body and leg muscle mass volumes (P= 0.071 and 0.0108, respectively), serum hemoglobin (P 〈 0.001), IPSS voiding subscore (P = 0.0418), and the second question on I IEF-5 (P = 0.0049). There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.展开更多
In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total te...In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l^-1 for a decreased ability/frequency to perform sex, 12.55 nmol l^-1 for decreased frequency of morning erections, and 14.35 nmol l^-1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l^-1, respectively. TT 〈13.21 nmol l^-1 (OR =1.4, 95%Ch 1.0-1.9, P= 0.037) or CFT 〈268.89 pmol l^-1 (OR - 1.5, 95%Ch 1.1-20, P=0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels 〈13.21 nmol l^-1 and CFT levels 〈268.89 pmol l^-1. Our results may improve the diagnostic accuracy of LOH in older men.展开更多
Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
Introduction: Hypogonadism should be suspected in a man who has symptoms and signs of testosterone deficiency. Clinical manifestations depend on the severity and duration of testosterone deficiency, whether the testic...Introduction: Hypogonadism should be suspected in a man who has symptoms and signs of testosterone deficiency. Clinical manifestations depend on the severity and duration of testosterone deficiency, whether the testicular deficit is concerning only androgen synthesis, spermatogenesis, or both. The objective of our study was to evaluate the clinical and aetiological characteristics of male hypogonadism in Dakar’s suburb. Patients and methods: We conducted a transversal study from January 1<sup>st</sup>, 2020 to July 31<sup>st</sup>, 2022. We included all male patients aged at least 14 years old with hypogonadism confirmed by a low level of early-morning free testosterone based on two different dosages. For all patients included, sociodemographic and diagnostic parameters were collected by using a pre-established registration form. Results: In total, 20 patients were selected. The average age was 36.3 years old [14 - 62 years old]. Half of the patients were overweight. Five patients had an abdominal circumference greater than 94 cm (37 inches). The other comorbidities found in our patients were type 2 diabetes (n = 1), hypertension (n = 1) and primary hypercholesterolemia in 2 patients. The functional signs reported by the patients were: couple’s infertility in 17 patients, decreased libido in 14 patients, erectile dysfunction in 13 patients, premature ejaculation in 2 patients and anejaculation in 4 patients. The physical examination revealed a bilateral testicular atrophy in 17 patients and a unilateral testicular atrophy in 2 patients;no patient had varicocele or urethral meatus abnormalities. Ten patients presented a micropenis. A eunuchoid morphotype was present in 6 patients and a short stature was noted in 2 patients. It was peripheral hypogonadism (HH) in 18 patients and hypogonadotropic hypogonadism (Hh) in 2 patients. The hypogonadotropic hypogonadism was isolated in both cases. The testicular echography confirmed testicular atrophy and showed cryptorchidism in 5 patients. The pituitary MRI performed in 2 patients with Hh showed an aspect of empty sella turcica in one patient and was normal in the second patient. Conclusion: In our practice, the diagnosis of male hypogonadism is most often made in adulthood. The most usual clinical presentation is failure of pubertal sexual development associated or not with a eunuchoid morphotype. The anomalies of spermatogenesis are found in most patients. Infertility is the primary motive for consultation.展开更多
BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent seps...BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.展开更多
We conducted an analysis of the Kallmann syndrome 1 (KAL-1) genotype in 17 patients with Kallmann syndrome (KS), 9 patients with normosmic idiopathic hypogonadotropic hypogonadism (nlHH) and 20 age-matched norma...We conducted an analysis of the Kallmann syndrome 1 (KAL-1) genotype in 17 patients with Kallmann syndrome (KS), 9 patients with normosmic idiopathic hypogonadotropic hypogonadism (nlHH) and 20 age-matched normal men in Northwestern China. To do this, we used multiplex PCR analysis with exon-flanking primers and automated sequencing techniques with peripheral blood DNA samples. Intragenic deletions were found at the KAL-1 locus in two KS patients. One case with an atrial septal defect exhibited an intragenic deletion of exon 6. Another KS patient with cryptorchidism had intragenic deletions of exons 5 and 6. For the nlHH patients, no abnormalities were observed in the exonic and flanking sequences of KAL-1. This report describes two intragenic deletions of KAL-1 in two KS patients and suggests that KAL-1 deletion might be more prevalent in KS patients with other congenital organ abnormalities than those described previously in other series from Northwestern China.展开更多
In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capasity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in moo...In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capasity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintanence of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS), and phosphodiesterase type-5 (PDE-5), which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintanence of penile tissue and erectile physiology as well. Furhermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalance, diagnosis and treatment options of hypogonadism in aging men.展开更多
The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numero...The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells(SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.展开更多
Objective:To investigate the change patterns of reproductive hormones in serum of aging males and the difference among male age brackets and the prevalence rates of late onset of hypogonadism(LOH) in males in Chinese ...Objective:To investigate the change patterns of reproductive hormones in serum of aging males and the difference among male age brackets and the prevalence rates of late onset of hypogonadism(LOH) in males in Chinese middle and aging males. Methods:Subjects included 1,498 men aged 40 to 69 from a county,and the serum reproductive hormones of 434 subjects were measured and calculated.In addition,the prevalence rates of LOH were analyzed by cut-off point of total testosterone(TT) and free testosterone(cFT),and screening scales(a questionnaire of androgen deficiency in the aging males(ADAM) and a scale of aging males’ symptoms(AMS)).TT,cFT,bio-available testosterone (Bio-T),luteinizing hormone(LH),sex hormone binding globulin(SHBG),testosterone secretion index(TSI), free testosterone index(FTD,the positive rates of LOH screening,androgen deficiency rates and the clinical prevalence rates of LOH were measured or calculated. Results:The serum TT levels did not change significantly with male aging while serum LH and SHBG levels gradually increased,but cFT,Bio-T,TSI and FTI levels gradually decreased with male aging.There was very significant difference in other six parameters of reproductive hormones(P<0.01),except for serum TT among the four age brackets(P>0.05).There was no correlation between serum TT levels and aging,LH levels(P>0.05). However,there was significantly a positive correlation between serum LH,SHBG and age(P<0.01),while there were negative correlation between cFT,Bio-T,TSI,FTI and age,LH levels(P<0.01).Moreover,SHBG level was positively correlated with LH level(P<0.01). Utilizing the Questionnaire of ADAM and AMS to screen subjects aged 40 to 69 years,mean positive rates of LOH screening were 80.77%and 32.34%respectively.Mean androgen deficiency rates were 14.02%and 43.69% by using TT and cFT cut-off point.In addition,mean LOH clinical prevalence rates of subjects on positive questionnaire results were 37.85%and 15.42%. Conclusion:The serum TT levels did not change significantly with male aging while serum LH,SHBG,cFT, Bio-T,TSI and FTI levels had the gradient change with aging.On the basis of Chinese population,however,the positive rate of LOH screening,androgen deficiency rate and clinical prevalence rate of LOH were obviously higher than that those of the other foreign studies.展开更多
Objective:Late-onset hypogonadism,or androgen deficiency in the aging male,is a significant cause of morbidity in older men.Many men in the low normal or equivocal range for low testosterone level exhibit signs and sy...Objective:Late-onset hypogonadism,or androgen deficiency in the aging male,is a significant cause of morbidity in older men.Many men in the low normal or equivocal range for low testosterone level exhibit signs and symptoms of hypogonadism.Serum testosterone is an imperfect maker for hypogonadism as symptoms vary greatly within the low to low normal range in addition to variations among testosterone assays.Perineal ultrasound can be effectively used to examine the bulbocavernosus muscle(BCM),an androgenized tissue that may be impacted by androgen receptor activity.Methods:This study was a retrospective analysis of men who underwent perineal ultrasound for hypogonadism.The ultrasound data were used to calculate the area of the BCM and correlate it with indices of hypogonadismin symptomatic men including free and total testosterone and dual-energy X-ray absorptiometry(DEXA).Results:The results demonstrate that there is a significant correlation between total and free testosterone and BCM area in hypogonadal patients.Comparison between BCM area and total testosterone showed R^2=0.061 and p=0.0187 and comparison between BCM area and free testosterone showed R^2=0.0957 and p=0.0034.In addition,low BCM was also correlated with DEXA results showing osteoporosis and osteopenia(R^2=0.2239,p=0.0027).Conclusion:There has been recent controversy over the safety of testosterone replacement therapy.This might be particularly important in men with hypogonadal symptoms but a low normal testosterone level.Our study investigated the use of perineal ultrasound to measure BCM as a surrogate marker for poor androgenized men presenting with hypogonadism.展开更多
Methods: Asystematic literature search was performed using PUBMED for all English articles up to April 2014. Although this review mainly focuses on published human studies, it also draws attention to where future rese...Methods: Asystematic literature search was performed using PUBMED for all English articles up to April 2014. Although this review mainly focuses on published human studies, it also draws attention to where future research should be directed based on animal studies. Results: Besides the 9 known mutations widely quoted for KS namely KAL1, Fibroblast growth factor 8 (FGF8), fibroblast growth factor receptor 1 (FGFR1), prokineticin 2 (PROK2), PROK receptor 2 (PROKR2), WDR11, heparin sulfate-6-O-Transferase (HS6T1), chromodomain helicase DNA binding protein 7 (CHD7) and semaphorin 3A (SEMA 3A), additional mutations in “FGF8 synexpression” group e.g., FGF 17, ILRD, DUSP 6, SPRY4 and FLRT3 have been shown to be involved in CHH, mostly KS besides SEMA 7A. Although traditionally division has been based on anosmic/normosnic criteria, further genes found to cause so called nIHH like Gonadotropin releasing hormone receptor (GNRHR). KISS1, TAC3, TACR3 have also been found to be associated with hyposmia on detailed testing on UPSIT and MRI for olfactory structures revealed absent OB. Further detailed examination of transcription factor genes have revealed involvement of HESX1, TSHZ1, AXL, SOX10 with a strong overlap of in transcription factors in development of septooptic dysplasia (SOD), combined pituitary hormone deficiency (CHPD) and KS. Treatment with rFSH/-hCG gives almost similar results to pulsatile GnRH therapy and should be based on cost factor, availability and in occasional cases specific treatment like kisspeptin therapy. Conclusions: Contrary to the traditional thinking, one shoud reconsider classifying cases of IHH simply on basis of anosmia/normosmia. Deafness calls for looking for mutations in Sox 10/CHD7/ILRD7 considering 38% association of former. Therapy should be individualized based on availability of pulsatile GnRH, cost factor and in recalcitrant cases kp therapy may be of use with kp mutations and NKB mutations.展开更多
The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a Pub Med literature s...The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a Pub Med literature search for the time period of 1989-2014, concentrating on 26 studies investigating the efficacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated that exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin(h CG) therapy or selective estrogen receptor modulators(SERMs), but may also include low dose h CG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of longterm data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, h CG therapy with or without testosterone supplementation represents an alternative treatment.展开更多
文摘Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.
文摘This study sought to investigate late-onset hypogonadism (LOH) in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms (AMS) scale and androgen deficiency in aging males (ADAM) questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors (total testosterone (TT), free testosterone (fT), sex hormone-binding globulin (SHBG) and bioavailability of testosterone (Bio-T)). There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results: TT was not related to aging (P〉O.05); levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.
文摘Although testosterone replacement therapy(TRT)is the first-choice method used worldwide for late-onset hypogonadism(LOH),clinical benefits are not seen in all cases.This study was conducted to determine the predictors of TRT efficacy for LOH.Fifty-six patients who visited our Men’s Health Clinic(Kawanishi City Medical Center,Kawanishi and Hyogo Medical University,Nishinomiya,Hyogo,Japan)between November 2003 and June 2021 with data available before and after TRT were enrolled.They were divided into responders(Group 1;n=45,accounting for 80.4%)and nonresponders(Group 2;n=11,accounting for 19.6%)based on the clinical response to TRT,including patient satisfaction.Factors noted before TRT included age,body mass index,aging males’symptoms score,sexual health inventory for men,luteinizing hormone,follicular-stimulating hormone,testosterone,free testosterone,prolactin(PRL),estradiol(E2),and testosterone/estradiol(T/E2)ratio in serum.For statistical analysis,a multivariable logistic regression model was used.Univariate analysis revealed PRL(odds ratio TORI:0.9624;95%confidence interval[Cl]:0.9316-0.9943,P<0.05),E2(OR:0.8692;95%Cl:0.7745-0.9754,P<0.05),and T/E2 ratio(OR:1.1312;95%Cl:1.0106-1.2661,P<0.05)to be predictive factors.Multivariate analyses showed that T/E2 ratio was an independent predictive factor(OR:1.1593;95%Cl:1.0438-1.2875,P<0.01).The present results suggest that a low value for T/E2 ratio may predict a reduced response to TRT.The T/E2 ratio threshold to predict nonresponders based on receiver-operating characteristics(ROC)curve analysis was shown to be 17.3.Although additional studies with larger number of patients are necessary,we propose the determination of serum E2 level and testosterone level prior to performing TRT.
文摘Introduction: Studies showed a high prevalence of metabolic abnormalities including dyslipidemia, type 2 diabetes in cases of low testosterone in men and which are associated with increased cardiovascular risk. Hypogonadism represents the second cause of endocrine osteoporosis. Objectives: The objectives of our work were: to determine the main causes of hypogonadism in women and men;to assess the frequency of metabolic and osteosdensitometric abnormalities in the hypogonadal population. Patients and methods: A retrospective descriptive study was carried out over 7 years on 120 patients, hospitalized in the Endocrinology department of the Hassan II University Hospital of Fez-Morocco for hypogonadism. The patients selected were those who had symptoms of hypogonadism confirmed in men by: low total testosterone for Tanner stage in adolescents, ng/ml or lower limit of normal for adults;in women, hypoestrogenia 30 pg/l. Gonadotropin dosage, karyotype, pelvic or testicular ultrasound and pituitary MRI, for etiological diagnosis, were performed. Bone densitometry was performed for bone impact and lipid profile for metabolic profile. Results: Out of 120 patients, there were 77 women and 43 men. The average age was 31.51 years. In men, the main causes were central hypogonadism in 67.4% and primary testicular failure in 32.6%. In women, central hypogonadism was also the most common cause noted in 63.7% and premature ovarian failure was observed in 36.4%. HypoHDL was significantly more frequent p (0.005) in women, osteopenia and osteoporosis were significantly more frequent in women than in men p (0.046). Conclusion: Central causes represent the most common etiology of hypogonadism in both sexes;abnormalities of bone mineralization and metabolic disorders were predominant in women.
文摘Gordon Holmes Syndrome is a rare inherited disease characterized by both neurological and reproductive signs and symptoms. Most patients develop neurologic challenges in early adulthood and cerebellar ataxia occurs as the disease progresses. In the majority of patients, hypogonadism is hypogonadotropic but rarely hypergonadotropic. We report a case of a 26-year-old female in Nigeria, with hypergonadotropic hypogonadism and cerebellar atrophy from a non-consanguineous marriage and no family history.
文摘The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone therapy.We aim to provide an updated and practical approach towards its management.We did a comprehensive literature search across MEDLINE(via PubMed),Scopus,and Google Scholar databases using the keywords“MOSH”OR“Obesity-related hypogonadism”OR“Testosterone replacement therapy”OR“Selective estrogen receptor modulator”OR“SERM”OR“Guidelines on male hypogonadism”as well as a manual search of references within the articles.A narrative review based on available evidence,recommendations and their practical implications was done.Although weight loss is the ideal therapeutic strategy for patients with MOSH,achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice.Therefore,androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity.However,there is conflicting evidence for the appropriate use of testosterone replacement therapy(TRT),and it can also be associated with complications.This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH.Before starting testosterone replacement in functional hypogonadism of obesity,it would be desirable to initiate lifestyle modification to ensure weight reduction.TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients.Balancing the risks and benefits of TRT should be considered in every patient before and during longterm management.
文摘Objective:Testosterone deficiency may be a risk factor for lower urinary tract symptoms(LUTS),and there may be a causal ink between the emergence of LUTS and the incidence of late-onset hypogonadism(LOH).We perfomed an epidemiologic study to investigate the association between symptomatic late-onset hypogonadism(SLOH)and LUTS in middle-aged and elderly rural Chinese males.Methods:A total of 965 men completed a questionnaire and underwent a detailed physical examination.The Aging Males'Symptoms(AMS)scale was used to assess SLOH,and the International Prostate Symptom Score(IPSS)questionnaire was used to assess LUTS.Serum reproductive hormone levels of testosterone,sex hormone-binding globulin(SHBG)and luteinizing hormone(LH)were measured.Results:A total of 965 males(mean age:56.34±8.85,range:40-80 years)were recruited for the present study.A total of 20.93%(202/965)were diagnosed with SLOH.A total of 93.16%(899/965)had mild LUTS,5.18%(50/965)had moderate LUTS,and 1.66%(16/965)had severe LUTS.Among SLOH patients,13.40%(27/202)and 3.90%(8/202)had moderate and severe LUTS,respectively.Patients with severe LUTS had increased SHBG and LH compared with those with mild and moderate LUTS(P<0.01).Correlation analysis revealed that the AMS total score was positively correlated with the IPSS score(P<0.05).The prevalence of SLOH was significantly increased with LUTS severity In addition to the known effect of age,the results of mutiple regression analysis also showed that serum LH or SHBG appeared to have a weak link with SLOH and LUTS that requires etiological and biological clarification in our future study.Conclusion:In this cross-sectional analysis of SLOH and LUTS,LUTS severity was significantly associated with hypogonadism symptoms.Additionally,the prevalence of SLOH advanced with increasing LUTS severity.Serum SHBG or LH showed a positive correlation with SLOH and LUTS.
文摘This study aimed to propose an operational definition of late-onset hypogonadism(LOH)that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China.A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China.Serum total testosterone(TT),sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were measured and free testosterone(cFT)was calculated.The Aging Males’Symptoms(AMS)scale was used to evaluate the LOH symptoms.Finally,5078 men were included in this analysis.The TT levels did not decrease with age(P=0.59),and had no relationship with AMS symptoms(P=0.87 for AMS total score,P=0.74 for≥3 sexual symptoms).The cFT levels decreased significantly with age(P<0.01)and showed a negative association with the presence of≥3 sexual symptoms(P=0.03).The overall estimated prevalence of LOH was 7.8%(395/5078)if a cFT level<210 pmol l−1 combined with the presence of≥3 sexual symptoms was used as the criterion of LOH.Among them,26.1%(103/395)and 73.9%(292/395)had primary and secondary hypogonadism,respectively.After adjustment for confounding factors,primary and secondary hypogonadism was positively related to age and comorbidities.Body mass index was an independent risk factor for secondary hypogonadism.The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone,and that the cFT level is more reliable than TT for LOH diagnosis.Secondary hypogonadism is the most common form of LOH.
文摘Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS), International Index of Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36) scale (P= 0.0318). ART was also associated with significant decreases in waist circumstance (P = 0.002) and serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body and leg muscle mass volumes (P= 0.071 and 0.0108, respectively), serum hemoglobin (P 〈 0.001), IPSS voiding subscore (P = 0.0418), and the second question on I IEF-5 (P = 0.0049). There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.
文摘In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l^-1 for a decreased ability/frequency to perform sex, 12.55 nmol l^-1 for decreased frequency of morning erections, and 14.35 nmol l^-1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l^-1, respectively. TT 〈13.21 nmol l^-1 (OR =1.4, 95%Ch 1.0-1.9, P= 0.037) or CFT 〈268.89 pmol l^-1 (OR - 1.5, 95%Ch 1.1-20, P=0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels 〈13.21 nmol l^-1 and CFT levels 〈268.89 pmol l^-1. Our results may improve the diagnostic accuracy of LOH in older men.
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
文摘Introduction: Hypogonadism should be suspected in a man who has symptoms and signs of testosterone deficiency. Clinical manifestations depend on the severity and duration of testosterone deficiency, whether the testicular deficit is concerning only androgen synthesis, spermatogenesis, or both. The objective of our study was to evaluate the clinical and aetiological characteristics of male hypogonadism in Dakar’s suburb. Patients and methods: We conducted a transversal study from January 1<sup>st</sup>, 2020 to July 31<sup>st</sup>, 2022. We included all male patients aged at least 14 years old with hypogonadism confirmed by a low level of early-morning free testosterone based on two different dosages. For all patients included, sociodemographic and diagnostic parameters were collected by using a pre-established registration form. Results: In total, 20 patients were selected. The average age was 36.3 years old [14 - 62 years old]. Half of the patients were overweight. Five patients had an abdominal circumference greater than 94 cm (37 inches). The other comorbidities found in our patients were type 2 diabetes (n = 1), hypertension (n = 1) and primary hypercholesterolemia in 2 patients. The functional signs reported by the patients were: couple’s infertility in 17 patients, decreased libido in 14 patients, erectile dysfunction in 13 patients, premature ejaculation in 2 patients and anejaculation in 4 patients. The physical examination revealed a bilateral testicular atrophy in 17 patients and a unilateral testicular atrophy in 2 patients;no patient had varicocele or urethral meatus abnormalities. Ten patients presented a micropenis. A eunuchoid morphotype was present in 6 patients and a short stature was noted in 2 patients. It was peripheral hypogonadism (HH) in 18 patients and hypogonadotropic hypogonadism (Hh) in 2 patients. The hypogonadotropic hypogonadism was isolated in both cases. The testicular echography confirmed testicular atrophy and showed cryptorchidism in 5 patients. The pituitary MRI performed in 2 patients with Hh showed an aspect of empty sella turcica in one patient and was normal in the second patient. Conclusion: In our practice, the diagnosis of male hypogonadism is most often made in adulthood. The most usual clinical presentation is failure of pubertal sexual development associated or not with a eunuchoid morphotype. The anomalies of spermatogenesis are found in most patients. Infertility is the primary motive for consultation.
文摘BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.
文摘We conducted an analysis of the Kallmann syndrome 1 (KAL-1) genotype in 17 patients with Kallmann syndrome (KS), 9 patients with normosmic idiopathic hypogonadotropic hypogonadism (nlHH) and 20 age-matched normal men in Northwestern China. To do this, we used multiplex PCR analysis with exon-flanking primers and automated sequencing techniques with peripheral blood DNA samples. Intragenic deletions were found at the KAL-1 locus in two KS patients. One case with an atrial septal defect exhibited an intragenic deletion of exon 6. Another KS patient with cryptorchidism had intragenic deletions of exons 5 and 6. For the nlHH patients, no abnormalities were observed in the exonic and flanking sequences of KAL-1. This report describes two intragenic deletions of KAL-1 in two KS patients and suggests that KAL-1 deletion might be more prevalent in KS patients with other congenital organ abnormalities than those described previously in other series from Northwestern China.
文摘In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capasity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintanence of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS), and phosphodiesterase type-5 (PDE-5), which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintanence of penile tissue and erectile physiology as well. Furhermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalance, diagnosis and treatment options of hypogonadism in aging men.
文摘The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells(SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.
文摘Objective:To investigate the change patterns of reproductive hormones in serum of aging males and the difference among male age brackets and the prevalence rates of late onset of hypogonadism(LOH) in males in Chinese middle and aging males. Methods:Subjects included 1,498 men aged 40 to 69 from a county,and the serum reproductive hormones of 434 subjects were measured and calculated.In addition,the prevalence rates of LOH were analyzed by cut-off point of total testosterone(TT) and free testosterone(cFT),and screening scales(a questionnaire of androgen deficiency in the aging males(ADAM) and a scale of aging males’ symptoms(AMS)).TT,cFT,bio-available testosterone (Bio-T),luteinizing hormone(LH),sex hormone binding globulin(SHBG),testosterone secretion index(TSI), free testosterone index(FTD,the positive rates of LOH screening,androgen deficiency rates and the clinical prevalence rates of LOH were measured or calculated. Results:The serum TT levels did not change significantly with male aging while serum LH and SHBG levels gradually increased,but cFT,Bio-T,TSI and FTI levels gradually decreased with male aging.There was very significant difference in other six parameters of reproductive hormones(P<0.01),except for serum TT among the four age brackets(P>0.05).There was no correlation between serum TT levels and aging,LH levels(P>0.05). However,there was significantly a positive correlation between serum LH,SHBG and age(P<0.01),while there were negative correlation between cFT,Bio-T,TSI,FTI and age,LH levels(P<0.01).Moreover,SHBG level was positively correlated with LH level(P<0.01). Utilizing the Questionnaire of ADAM and AMS to screen subjects aged 40 to 69 years,mean positive rates of LOH screening were 80.77%and 32.34%respectively.Mean androgen deficiency rates were 14.02%and 43.69% by using TT and cFT cut-off point.In addition,mean LOH clinical prevalence rates of subjects on positive questionnaire results were 37.85%and 15.42%. Conclusion:The serum TT levels did not change significantly with male aging while serum LH,SHBG,cFT, Bio-T,TSI and FTI levels had the gradient change with aging.On the basis of Chinese population,however,the positive rate of LOH screening,androgen deficiency rate and clinical prevalence rate of LOH were obviously higher than that those of the other foreign studies.
文摘Objective:Late-onset hypogonadism,or androgen deficiency in the aging male,is a significant cause of morbidity in older men.Many men in the low normal or equivocal range for low testosterone level exhibit signs and symptoms of hypogonadism.Serum testosterone is an imperfect maker for hypogonadism as symptoms vary greatly within the low to low normal range in addition to variations among testosterone assays.Perineal ultrasound can be effectively used to examine the bulbocavernosus muscle(BCM),an androgenized tissue that may be impacted by androgen receptor activity.Methods:This study was a retrospective analysis of men who underwent perineal ultrasound for hypogonadism.The ultrasound data were used to calculate the area of the BCM and correlate it with indices of hypogonadismin symptomatic men including free and total testosterone and dual-energy X-ray absorptiometry(DEXA).Results:The results demonstrate that there is a significant correlation between total and free testosterone and BCM area in hypogonadal patients.Comparison between BCM area and total testosterone showed R^2=0.061 and p=0.0187 and comparison between BCM area and free testosterone showed R^2=0.0957 and p=0.0034.In addition,low BCM was also correlated with DEXA results showing osteoporosis and osteopenia(R^2=0.2239,p=0.0027).Conclusion:There has been recent controversy over the safety of testosterone replacement therapy.This might be particularly important in men with hypogonadal symptoms but a low normal testosterone level.Our study investigated the use of perineal ultrasound to measure BCM as a surrogate marker for poor androgenized men presenting with hypogonadism.
文摘Methods: Asystematic literature search was performed using PUBMED for all English articles up to April 2014. Although this review mainly focuses on published human studies, it also draws attention to where future research should be directed based on animal studies. Results: Besides the 9 known mutations widely quoted for KS namely KAL1, Fibroblast growth factor 8 (FGF8), fibroblast growth factor receptor 1 (FGFR1), prokineticin 2 (PROK2), PROK receptor 2 (PROKR2), WDR11, heparin sulfate-6-O-Transferase (HS6T1), chromodomain helicase DNA binding protein 7 (CHD7) and semaphorin 3A (SEMA 3A), additional mutations in “FGF8 synexpression” group e.g., FGF 17, ILRD, DUSP 6, SPRY4 and FLRT3 have been shown to be involved in CHH, mostly KS besides SEMA 7A. Although traditionally division has been based on anosmic/normosnic criteria, further genes found to cause so called nIHH like Gonadotropin releasing hormone receptor (GNRHR). KISS1, TAC3, TACR3 have also been found to be associated with hyposmia on detailed testing on UPSIT and MRI for olfactory structures revealed absent OB. Further detailed examination of transcription factor genes have revealed involvement of HESX1, TSHZ1, AXL, SOX10 with a strong overlap of in transcription factors in development of septooptic dysplasia (SOD), combined pituitary hormone deficiency (CHPD) and KS. Treatment with rFSH/-hCG gives almost similar results to pulsatile GnRH therapy and should be based on cost factor, availability and in occasional cases specific treatment like kisspeptin therapy. Conclusions: Contrary to the traditional thinking, one shoud reconsider classifying cases of IHH simply on basis of anosmia/normosmia. Deafness calls for looking for mutations in Sox 10/CHD7/ILRD7 considering 38% association of former. Therapy should be individualized based on availability of pulsatile GnRH, cost factor and in recalcitrant cases kp therapy may be of use with kp mutations and NKB mutations.
文摘The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a Pub Med literature search for the time period of 1989-2014, concentrating on 26 studies investigating the efficacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated that exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin(h CG) therapy or selective estrogen receptor modulators(SERMs), but may also include low dose h CG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of longterm data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, h CG therapy with or without testosterone supplementation represents an alternative treatment.