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.

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.

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.

Hypogonadism and erectile dysfunction： an overview

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.

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.

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.

中国健康男子迟发性睾丸功能减退的症状评价

目的:调查40岁以上中国健康男子出现症状与雄激素的关系,制定一份新的迟发睾丸功能减退(LOH)症状调查表。方法:设计1份18个问题的症状问卷,在北京、上海、西安和重庆4个城市调查40岁以上健康男子637人,同时测定血清总睾酮、计算的游离睾酮、睾酮分泌指数和游离睾酮指数,分析症状与上述指标的相关性。结果:12项症状与上述4项指标中的2项或以上显著相关,组成了1份新的症状筛查调查表,其灵敏度为70%,特异度为46%。结论:调查表70%的灵敏度达到了筛查的要求,特异度较低可能与个体反应差异以及其他与年龄相关激素,如GH-IGF-1、DHEA、甲状腺激素、褪黑激素和瘦素等的变化有关。

症状性迟发型性腺功能减退合并勃起功能障碍患者血清生殖激素分析

目的·通过观察症状性迟发型性腺功能减退（SLOH）合并勃起功能障碍（ED）患者血清生殖激素变化情况,探讨生殖激素与SLOH合并ED（SLOH/ED）的相关关系。方法·采用问卷调查的方式,经整群及年龄分层多阶段不等比例的随机抽样方法,抽取3 000例40～80岁有固定性伴侣的社区中老年男性作为研究对象。采用老年男性症状（AMS）量表评估SLOH及其严重程度,采用国际勃起功能指数问卷表-5（IIEF-5）评估勃起功能,同时检测血清总睾酮（TT）、游离睾酮（FT）、黄体生成素（LH）和性激素结合球蛋白（SHBG）水平,计算生物活性睾酮（Bio-T）水平,单因素和多因素Logistic回归分析生殖激素与SLOH/ED的相关关系。结果·共获得2 588例符合条件的完整研究资料,平均年龄（57.95±8.50）岁。930例（35.94%）男性观察到SLOH（AMS≥27）症状,其中812例（31.38%）男性同时存在ED。739例（28.56%）男性既无SLOH亦不存在ED症状。Logistic回归分析显示TT及FT水平与SLOH/ED的相关关系不明显,年龄、SHBG和Bio-T与SLOH/ED的相关关系有统计学意义（P〈0.01）。结论·SHBG和Bio-T与SLOH/ED显著相关,能准确反映SLOH/ED患者的皿清生殖激素水平。

restosterone replacement therapy for late-onsel lypogonadism： current trends in Korea

Testosterone levels in men older than 40 years can decrease at a rate of 1%-2% per year, and reports show that more than 50% of 80-year-old men have testosterone levels consistent with hypogonadism. Late-onset hypogonadism （LOH） is a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms of serum testosterone deficiency. In recent decades, the concept of LOH in ageing men has become familiar in European countries and the United States. It is also a topic of interest and debate throughout Korea. However, most of the data regarding advantages or disadvantages of testosterone replacement therapy （TRT） as treatment for LOH have been primarily obtained from studies on Western populations; therefore, studies of the effects of TRT in Asian men, who may have different serum testosterone compared to Western men, are needed. TRT is commonly prescribed in Korea, despite the paucity of studies on the effects of TRT in Asian populations. Data from various TRT studies based on Korean have shown its efficacy in increasing serum testosterone levels and improving subjective symptoms as assessed by questionnaires. Currently, patches and short-acting intramuscular injections are displaced by gels and long-acting formulations. However, to prevent overdiagnosis and overtreatment, indication for TRT should include both low testosterone levels and symptoms and signs of hypogonadism.

Effects of Guhanyangshengjing Tablet on Testosterone Synthesis and Expression of SYCP3 in the Testis of Aging Male Rats

Objective: The objective of this article is to investigate the effect of Guhanyangshengjing Tablet (GT) on expression of synaptonemal complex protein 3 (SYCP3), a meiotic marker, in the testis tissue of aging male rats. Methods: Forty aging male rats were randomly assigned into 4 equal groups (n = 10 per group). Rats in each group were treated with GT at dose of 0 (control), 1.5 g/kg, 3.0 g/kg or 4.5 g/kg respectively by gavage daily for 30 days. At the end of the experiment, all animals were sacrificed and the blood samples were drawn to evaluate serum testosterone levels. The reproductive organs of each rat were taken and weighted. The right testis of each rat was removed for the analysis of intratesticular testosterone (ITT) concentrations, and the left one was used for immunohistochemical staining. Results: Compared with the control, reproductive organs’ weights, serum testosterone levels, ITT concentrations, quality of sperm, and expression of SYCP3 in the GT-treated groups were all improved in a dose-dependent manner. Conclusion: GT can improve testosterone synthesis and promote spermatogenesis simultaneously, indicating that GT is suitable for late-onset hypogonadism (LOH) patients with fertility requirements.

Current Situation and Reconsideration on Study of Integrated Chinese and Western Medicine Andrology

The development of Chinese medicine and Western medicine andrology is based on different social background and academic systems,either Chinese medicine or Western medicine andrology has their limitations,therefore,integration of Chinese and Western medicine(ICWM)andrology is in a great need.After more than 30 years of development,andrology has made great achievements in the construction of specialized academic association,holding academic conferences and publication of academic monographs,and the research progress on this field is mainly in the combination of disease and syndrome,microdifferentiation of symptoms and signs and basic research development.However,the comprehensive theoretic system of ICWM andrology has not yet established,and the related studies are still on the primary stage.In the future studies,great efforts still need to be made to expand the methods for the investigation of ICWM,and make innovations in the field of andrology.

Effects of Saikokaryukotsuboreito on Spermatogenesis ant Fertility in Aging Male Mice

Background： Aspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism （LOH） patients desiring fertility. Saikokaryukotsuboreito （SKRBT） is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice. Methods： Thirty aging male mice were randomly assigned to three groups, Mice were orally administered with phosphate-buffer solution or SKRBT （300 mg/kg, daily） or received testosterone by subcutaneous injections （10 mg/kg, every 3 days）. Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. lntratesticular testosterone （ITT） levels, quality of sperm, expression of synaptonemal complex protein 3 （SYCP3）, and fertility were assayed. Results： In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group （ITT： 85.50 ＋ 12.31 ng/g vs. 74.10 ±11.45 ng/g, P = 0.027; sperm number： [ 14.94 ± 4.63] × 106 cells/ml vs. [8.79±4.38] × 106 cells/ml, P = 0.002; sperm motility： 43.16 ± 9.93% vs. 33.51 ± 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule： 77.50 ± 11.01 ng/ml vs. 49.30 - 8.73 ng/ml, P 〈 0.001 ; the expression of SYCP3 protein： 1.23± 0.09 vs. 0.84 ± 0.10, P 〈 0.001 ）, but fertility was not significantly changed （P 〉 0.05, respectively）. In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group （ITT： 59.00 ±8.67, P = 0.005; sperm number： [4.34 ± 2.45] 100 cells/ml, P = 0.018： sperm motility： 19.53 ± 7.69%, P = 0.001 ; the number of SYCP3-positive cells/tubule section 71.98 ：k 8.88%, P= 0.001 ; the expression of SYCP3 protein： 30.00 ± 11.28, P 〈 0.001 ; the percentage of SYCP3-positive tubules/ 0.71± 0.09, P 〈 0.001 ）, and fertility was also suppressed （P 〈 0.05, respectively）. Conclusion： SKRBT had no adverse effect on fertility potential in aging male mice