Erectile function and late-onset hypogonadism symptoms related to lower urinary tract symptom severity in elderly men

The aim of this study was to evaluate the relationship between lower urinary tract symptoms （LUTSs）, erectile dysfunction （ED） and symptomatic late-onset hypogonadism （SLOH） in ageing men in the Aegean region of Turkey. Five hundred consecutive patients 〉40 years old who had been in a steady sexual relationship for the past 6 months and were admitted to one of six urology clinics were included in the study. Serum prostate-specific antigen and testosterone levels and urinary flow rates were measured. All patients filled out the International Prostate Symptom Score and Quality of Life （IPSS-QoL）, International Index of Erectile Function （IIEF） and Aging Males＇ Symptoms （AMS） scale forms. Of the patients, 23.9% had mild LUTSs, 53.3% had moderate LUTSs and 22.8% had severe LUTSs. The total testosterone level did not differ between groups. Additionally, 69.6% had ED. The presence of impotence increased with increasing LUTS severity. Symptomatic late-onset hypogonadism （AMS 〉27） was observed in 71.2% of the patients. The prevalence of severe hypogonadism symptoms increased with the IPSS scores. A correlation analysis revealed that all three questionnaire scores were significantly correlated. In conclusion, LUTS severity is an age-independent risk factor for ED and SLOH. LUTS severity and SLOH symptoms appear to have a strong link that requires etiological and biological clarification in future studies.

How to recognize late-onset hypogonadism in men wit sexual dysfunction

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.

Survey for late-onset hypogonadism among old anti middle-aged males in Shanghai communities

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.

Late-onset hypogonadism： current concepts and controversies of pathogenesis, diagnosis and treatment

Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g. loss of vigor and frailty） and psychological （e.g., depression） symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male （PADAM）. Late-onset hypogonadism （LOH） describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure （low T, high luteinizing hormone （LH）） or secondary to a hypothalamic-pituitary failure （low T, low or inappropriately normal LH）. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases （e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty）. A problem with the diagnosis of LOH is that often the symptoms （in 20%-40% of unselected men） and low circulating T （in 20% of men 〉70 years of age） do not coincide in the same individual. The European Male Ageing Study （EMAS） has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T （total T 〈11 nmol 1-1 and free T 〈220 pmol 1-1） and three sexual symptoms （erectile dysfunction, and reduced frequency of sexual thoughts and morning erections）. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short- and long-term risks, is not yet available. In this review, we will summarize the current conceets and controversies in the Dathogenesis, diagnosis and treatment of LOH.

Predictive factors for efficacy of testosterone replacement therapy for late-onset hypogonadism in Japanese men:a preliminary report

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.

Male and Female Hypogonadisms: Etiological, Metabolic and Osteodensitometric Aspects

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.

Hypergonadotrophic Hypogonadism with Cerebellar Ataxia in a Twenty-Six-Year-Old Female: A Case Report

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.

Management of male obesity-related secondary hypogonadism:A clinical update

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.

Association of symptomatic late-onset hypogonadism and lower urinary tract symptoms in aging males: a community-based study

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.

Prevalence of late-onset hypogonadism among middle-aged and elderly males in China:results from a national survey

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.

Late-onset hypogonadism： beyond testosterone

Late-onset hypogonadism is defined as a combination of low testosterone （T） levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell （dys）function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone （LH） and 25-hydroxyvitamin D levels. These markers help in identifying the so-called ＂subclinical＂ hypogonadism （normal T, high LH levels）. Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option （cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D） in these patients. We studied 66 patients with classic hypogonadism （total T [TT] 〈12 nmol I-~, LH 〉 8 IU 1-1） （n = 26） and subclinical hypogonadism （TT 〉 12 nmol I-＊, LH 〉 8 IU I-~） （n = 40） and low 25-hydroxyvitamin D （〈50 nmol I-1）. Subjects received cholecalciferol （5000 IU per week） （n = 20） or calcidiol （4000 IU per week） （n -- 46）, and 25-hydroxyvitamin D and parathyroid hormone （PTH） were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PI＂H levels in both groups of men with hypogonadism （primary, n = 16 and subclinical, n = 30）, whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D （calcidiol）, and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.

Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism： a multicenter, randomized controlled trial in Japan （EARTH Study）

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.

Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China

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.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

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.

Diagnosis of Male Hypogonadism: Experience of a Subsaharan African Endocrinology Department: Transversal Study from January 1st, 2020 to July 31st, 2022

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 1st, 2020 to July 31st, 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.

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

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.

New understandings of the genetic basis of isolated diopathic central hypogonadism

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

Molecular analysis of KAL-1 in a series of Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism patients from Northwestern China

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.