迟发性睾丸功能减退的筛查、诊断、治疗和监测(二)

四、诊断 LOH的诊断包括三个方面内容：（1）症状评价；（2）血清睾酮测定；（3）试验性睾酮补充治疗的反应。三者是统一和相互相成的，单纯有症状或血清睾酮水平降低，对睾酮补充治疗无反应的患者不能诊断LOH，应该进一步检查可能引起症状的其它原因。     

迟发性睾丸功能减退筛查量表的研究与应用现状

随着迟发性睾丸功能减退(LOH)研究的深入,LOH筛查量表研究逐渐完善。常用筛查量表有AMS量表、ADAM问卷、MMAS问卷,量表的主要作用是筛查或者诊断LOH以及治疗效果的评估,目前研究主要集中在量表的应用、敏感性和特异性的验证、量表评价结果或者某些项目与血清激素水平之间的相关性、不同量表之间的比较等方面。本文综述筛查量表的研究、应用现状,并对其敏感性、特异性进行了总结。     

迟发性睾丸功能减退的筛查、诊断、治疗和监测

在19世纪40年代，Werner通过敏锐而深入的临床观察发现，男子在50岁以后出现体能下降、容易疲劳、记忆力减退、注意力不集中、烦躁不安、郁抑、潮热、阵汗和性功能减退等症状，命名为男子更年期综合征（male climacteric）。Bauer认为男子更年期综合征的命名是用词不当，上述症状是睾丸功能减退的表现。Heller等提出，只有尿促性腺激素水平增高的患者才能诊断男子更年期综合征。     

老年男性勃起功能及迟发性性腺功能减退症状与下尿路症状严重性的关系

本文旨在研究土耳其爱琴海地区的老年男性下尿路症状（LUTSs）、勃起功能障碍（ED）和有症状的迟发性性腺功能减退症（SLOH）三者间的关系。符合以下标准的500名男性患者被纳入该研究：40周岁以上；过去6个月内有稳定的性关系；在六个泌尿外科诊所之一进行过就诊登记。每位患者均行血清PSA、睾酮水平及尿流率的检测，并填写国际前列腺症状评分和生活质量评分（IPSS-QoL）量表、国际勃起功能指数（IIEF）问卷和老年男性症状（AMS）量表。在所有的研究对象中，23．9％的患者有轻度LUTSs，53．3％有中度LUTSS，22．8％有重度LUTSS。每组间总睾酮水平无明显差异。除此之外，69．6％的病人患有ED，且ED的发生率与LUTS严重性呈正相关。71．2％的患者出现SLOH（AMS〉27），且IPSS评分越高，严重的性腺功能减退症状的发生率也越高。相关性分析显示以上三种问卷分数之间有显著关联。总之，LUTS严重性是ED和SLOH的非年龄依赖性危险因素，LUTS严重性和SLOH症状之间似乎有显著的相关性，但还需要从病因学和生物学角度进行深入阐明。     

十一酸睾酮与补肾通脉方合用治疗男性迟发性性腺功能减退的临床观察

<正>男性迟发性性腺功能减退(late onset hypogonadism,LOH)是指男性步入40岁以后,在青年期达到高峰后体内的雄激素随着年龄增长而下降,由此引起一系列生理变化及临床症状~([1])。随着医学临床研究的深入,LOH越来越受到医界及社会的关注。2007-2009年,由原国家人口计划生育委员会科研所男性临床研究室主任谷翊群教授发起并主持的国内首个针对中老年男性的健康状况调研评估数据     

十一酸睾酮胶丸改善糖尿病合并迟发性性腺功能减退患者胰岛素抵抗的临床研究

目的:探讨睾酮替代治疗对糖尿病合并迟发性性腺功能减退患者胰岛素抵抗的作用及其临床疗效。方法:82例糖尿病合并迟发性性腺功能减退患者随机分为睾酮治疗组(n=42)和对照组(n=40),两组患者均维持原有降糖、调脂治疗方案,治疗组在此基础上予十一酸睾酮胶丸口服,共治疗6个月,观察两组治疗前后体重指数、腰围、血糖、血脂谱、胰岛素敏感性、生殖激素以及中老年男性症状问卷(AMS)评估的相关症状评分及IIEF-5评分变化。结果:与治疗前相比,治疗组干预后体重指数(26.71±2.39 vs 25.15±2.28,P0.05)、腰围(cm)(89.96±9.13 vs 85.03±9.58,P0.05)、糖化血红蛋白(%)(7.73±1.31 vs 7.01±1.25,P0.05)、甘油三酯(mmol/L)(1.97±0.83 vs 1.41±0.69,P0.05)显著下降,总睾酮(μmol/L)(7.16±2.21 vs 14.22±2.63,P0.05)显著升高,稳态模型评估的胰岛素抵抗指数(3.76±1.18 vs 2.55±1.03,P0.05)和胰岛素敏感指数(96±51 vs 138±53,P0.05)显著改善,AMS心理和躯体评分显著改善(P0.05),但IIEF-5评分(13.28±6.38 vs14.95±6.08,P0.05)改善不明显。结论:睾酮替代治疗可以改善糖尿病合并迟发性性腺功能减退患者胰岛素抵抗并具有确切临床疗效。     

迟发性性腺功能减退症合并下尿路症状患者的睾酮补充治疗

<正>男性迟发性性腺功能减退症(LOH)是一种与男性年龄增长相关的临床和生物化学综合征,其特征为具有典型的临床症状和血清生物活性睾酮水平的低下,严重影响生活质量,并给多器官、系统的功能带来不良影响。受LOH影响的患者也是良性前列腺增生下尿路症状(LUTS)高发人群。对于以勃起功能障碍(ED)为主要表现的LOH,且同时合并良性前列腺增生LUTS患者给予睾酮补充疗法,能否同时改善勃起功能和LUTS或者加重LUTS值得     

迟发性脑功能障碍2例

对不合并脑外伤的患者，发生迟发性脑功能障碍，临床少有报道。笔者遇到2例，现将资料报告如下。     

合肥市成年男性迟发性性腺功能减退认知水平的调查

目的 调查合肥市成年男性对迟发性性腺机能减退(LOH)的认知水平及其影响因素.方法 发放问卷调查1500名成年男性的基本情况,对LOH基本情况的认知,对LOH治疗的认识,希望通过什么途径了解LOH以及对LOH诊疗的态度.并比较分析年龄和文化程度对这些结果的影响.结果 本研究共收集有效可评价问卷及填写完整者1135(75.7%)份.被调查者中只有256人(22.6%)自述听说过LOH,仅有78人(6.9%)回答知道十一酸睾酮补充疗法.年龄较大组及高中以上组对LOH的基本认知率及对LOH知识的需求较高.学历较低组倾向于选择广播电视等来了解LOH的知识,而学历高者喜欢医务人员讲解等方式.年龄较小组偏重于寻求医院及药房的帮助,年龄较大者则更希望得到医务人员、保健品等的帮助.学历较低者倾向于选择保健品、药房,而学历高者喜欢医务人员的建议等方式来处理LOH.结论 合肥市成年男性对LOH的认知水平很低,不同年龄段和不同文化程度者对诊疗的态度不同,并选择也获取LOH知识的途径不同.     

雄蚕益肾方对雄性迟发性性腺功能减退大鼠睾丸组织生物钟基因表达的影响

目的:探讨雄蚕益肾方对雄性迟发性性腺功能减退症(LOH)大鼠睾丸组织细胞生物钟基因表达的影响。方法:48只8周龄雄性SD大鼠随机分为正常组，模型组，丙酸睾酮组，雄蚕益肾方低、中、高剂量组。模型组，丙酸睾酮组，雄蚕益肾方低、中、高剂量组大鼠腹腔注射480 mg/(kg·d)D-半乳糖(D-gal),连续注射56 d进行LOH造模，正常组大鼠每日腹腔注射相同体积生理盐水。造模成功后，雄蚕益肾方低、中、高剂量组分别给予10.4、20.8、41.6 g/(kg·d)体重剂量的雄蚕益肾方中药汤剂灌胃，每组每日均早、晚各灌胃1次；丙酸睾酮组大鼠肌注5.21 mg/(kg·d)体重剂量的丙酸睾酮，每周3次；正常组和模型组给予相同体积的蒸馏水灌胃；各组均连续操作28d。实验结束后，采血离心取上清液ELISA法检测睾酮(T)水平，取睾丸组织进行RT-qPCR、Western印迹分别检测BMAL1、NR1D1、PER2、CRY1、StAR、CYP11A1 mRNA表达量和蛋白表达水平。结果:模型组大鼠血清睾酮水平、睾丸组织BMAL1、NR1D1、PER2、CRY1、StAR、CYP11A1在mRNA表达量...     

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.     

男性性腺功能低减病人尿β-FSH排泄连续测定

目的 :连续观察男性性腺功能低减病人尿卵泡刺激素 β亚单位 (β FSH)的排泄 ,探讨其对男性性腺功能低减的临床分类诊断和病理生理机制研究的意义。　方法 :4例健康成年男性 (年龄分别为 19、2 2、2 7、33岁 )、4例低促性腺激素型性腺功能低减男性病人 (年龄分别为 17、17、19、2 4岁 )和 5例高促性腺激素型性腺功能低减男性病人 (年龄分别为 16、16、17、2 0、2 2岁 ) ,连续留晨尿 30～ 32d ,其中 1例正常男性留取标本 6 3d。酶免法测定尿 β FSH ,以肌酐 (Cr)含量进行校正。　结果 :4例正常成年男性尿 β FSH总平均为 (1.16± 0 .2 0 ) μg/mgCr,均可出现波峰 ,最大峰值为 2 .76 μg/mgCr。 4例低促性腺激素型性腺功能低减男性病人 [Kallmann或特发性低促性腺激素型性腺功能低减 (IHH) ]尿 β FSH分别为 (0 .5 8± 0 .31)、(0 .93± 0 .4 7)、(0 .4 7± 0 .33)、(0 .6 0± 0 .4 0 ) μg/mgCr,曲线上未见明显波动。 5例高促性腺激素型性腺功能低减男性病人 (Klinefelter)尿 β FSH分别为 (3.0 2± 0 .93)、(4.36± 1.12 )、(4.79± 0 .78)、(4.6 4± 1.4 2 )、(3.88± 1.4 2 ) μg/mgCr,曲线上出现显著不规则波动 ,最大峰值达6 .83μg/mgCr。所有病人第二性征发育差 ,血清T水平显著低下。低促性腺激素?     

中药联合安特尔治疗迟发性睾丸功能减退30例疗效观察

目的探讨中药联合安特尔治疗迟发性睾丸功能减退的有效性。方法将60例迟发性腺功能减退症患者随机分成两组，治疗组30例采用逍遥散合菟丝子丸加减联合安特尔治疗，对照组30例单纯采用安特尔治疗，两组均治疗3个月，观察患者治疗前后PADAM评分、PSA的变化，并对其进行疗效评估。结果治疗组有效率明显高于对照组，两组比较差异有显著性（P〈0．05）。结论中药联合安特尔可能明显改善患者的性腺功能减退症状，较单纯应用安特尔疗效为佳。     

选择性雄激素受体调节剂治疗迟发性男性性腺功能低下症

几种睾酮制剂用于治疗老年男性性腺功能减退。这些疗法在其便利性、灵活性、区域供应和费用等方面有区别,但有共同的药代动力学基础,同时缺乏长期安全性数据。简洁和成本较低的基于药代动力学的注册临床试验使得开发改善性的治疗迟发性性腺功能减退的新疗法的商业动机减少了。在前列腺、头发、皮肤受雄激素缺乏影响的患者中,选择性雄激素受体调节剂已被证明可以提供合成代谢的好处。（目前,选择性雄激素受体调节剂的临床进展集中在有限定身体功能的临床终点的急性肌肉萎缩和低体重）。在具有有益的药理、理想的药代动力学的选择性雄激素受体调节剂应用于治疗迟发性男性性腺功能低下症前,其在男性性腺功能低下治疗中关于临床缺陷的更清晰的监管是必须的。     

Testicular Findings, Endocrine Features and Therapeutic Responses of Men with Acquired Hypogonadotropic Hypogonadism

Background Men with acquired hypogonadotropic hypogonadism (AHH) who desire restoration of fertility are treated with exogenous gonadotropin. However, gonadotropin (Gn) therapy does not always restore testicular function. It is unknown whether the therapeutic responses to Gn therapy correlate with their testicular histological findings. Thus, we analyzed factors influencing testicular dysfunction and therapeutic responses in AHH.
Methods Of 21 men with AHH, 11 had no postmeiotic germ cells and were classified as the severe spermatogenic failure group. These were compared with the other 10 patients who had postmeiotic germ cells and comprised the mild spermatogenic failure group.
Results: Testicular volume and tubular diameter were significantly smaller, and the basement membrane and tunica propria were significantly thicker in the severe failure group. The gonadotropin basal level and response to exogenous gonadotropin-releasing hormone, and the testosterone response to exogenous human chorionic gonadotropin were significantly lower in the severe failure group of patients. Also, the recovery of spermatogenesis and testosterone secretory potentials was poor in the cases with a duration between diagnosis and treatment of 2 years or more.
Conclusion Longer periods without treatment may be responsible for irreversible testicular dysfunction in AHH. Gn therapy should be initiated very soon after the diagnosis of AHH if fertility is desired.     

Prolactin Secretion in Adolescent Boys with Hypogonadism

Basal and TRH stimulated plasma prolactin levels were determined in 24 pubertal boys with hypogonadism (Primary: n = 10; secondary: n = 4; tertiary (hypothalamic): n = 10) and controls matched for pubertal stage (n = 12). The differentiation between secondary and tertiary hypogonadism was made with the help of a prolonged LRH test. The TRH test was performed by injecting 200 mcg i.v. in one bolus and taking plasma samples at 0, 15, 30, 60 and 90 minutes. No statistically significant differences were found between any of the groups. It is concluded that determination of basal or TRH stimulated prolactin does not contribute to clarify the etiology of hypogonadism or to determine the grade of damage or dysfunction in the hypogonadic testes.     

雄激素对男性性腺功能低减病人促红细胞生成素的影响

目的 :观察雄激素替代治疗对性腺功能低减男子促红细胞生成素 (EPO)的影响 ,探讨雄激素促进红细胞和血红蛋白生成增加的机制。　方法 :8例原发性性腺功能低减 (Klinefelter综合征 )病人 ,接受初次 5 0 0mg或10 0 0mg十一酸睾酮 (TU)肌肉注射 ,间隔 3个月后交叉剂量第二次注射。注射前后观察血清性激素水平的变化 (放免法 ) ;在注射前和后的第 4、8周分别查血常规和红细胞比容 ,酶免疫法测定血清EPO。　结果 :注射TU后 ,第二性征发育情况改善 ,血睾酮水平显著升高 ,注射后 1周达峰值 ,维持有效治疗的雄激素水平 (>10nmol/L)超过 6周。血红细胞计数、红细胞比容和血红蛋白含量的均数均有不同程度的增加趋势 ,但统计学上差异不显著 (P >0 .0 5 )。与治疗前相比 ,注射TU后EPO水平显著升高 ,并维持 8周以上 (P <0 .0 1～ 0 .0 5 ) ;第 2次注射TU仍然使EPO水平升高。　结论 :雄激素替代治疗使性腺功能低减男子EPO水平升高 ,是红细胞生成增加的机制之一。     

Are there symptom‐specific testosterone thresholds in aging men?

Study Type – Prognosis (retrospective cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Late onset hypogonadism is a syndrome combining low testosterone levels and clinical symptoms. But specific testosterone levels as well as clinical symptoms (e.g. sexual dysfunction) are poorly defined and still under debate. This study explores the association between testosterone levels and clinical symptoms with regard to co‐morbidities such as obesity, smoking and age. A main focus in this study is to investigate the influence of age on late onset hypogonadism, as many symptoms, which are correlated to low testosterone, might reflect just a normal process of aging. Finally the results show that only few symptoms (mainly psychosomatic symptoms) are associated with low testosterone and all other symptoms are significantly associated with age.

OBJECTIVE

? To study the association between specific clinical symptoms (e.g. low libido and erectile dysfunction) and testosterone levels and age in order to define symptom‐specific testosterone thresholds.

MATERIALS AND METHODS

? Serum samples for testosterone determination were obtained from 675 healthy men. ? Participants underwent urological examination and completed the Aging Males Symptoms scale, the Beck Depression Index and the International Index of Erectile Function. Overall scores and those from individual questions from the questionnaires were evaluated. ? Testosterone levels in men with symptoms were compared with those in men without symptoms. ? The risks of clinical symptoms were evaluated using univariate, multiple multinomial regression analyses and Bonferroni correction.

RESULTS

? Significant associations between testosterone levels and a number of androgen deficiency symptoms were seen at testosterone levels of 13.5–14.4 nmol/L, but multiple logistic regression analysis revealed confounding effects with age. ? Symptoms such as loss of libido, lack of vigour and sexual dysfunction were associated with age rather than with testosterone. ? Erectile dysfunction was reported at testosterone levels between 14.65 nmol/L and 14.8 nmol/L, but was again significantly associated with age rather than testosterone levels. ? The severity of symptoms significantly increased with decreasing testosterone levels using univariate analysis, but only the relationship with psychological symptoms remained significant after Bonferroni correction.

CONCLUSION

? In aging males, androgen deficiency symptoms were reported at normal levels of testosterone, but age was an important confounder. Symptom‐specific testosterone thresholds could not be defined.