雄激素受体基因CAG多态性对男性激素避孕有效性影响的研究

目的：分析应用肌注十一酸睾酮酯（TU）进行激素避孕的男性志愿者中起反应者与不起反应者雄激素受体（AR）基因（CAG）n微卫星多态性，并探讨该多态性对激素避孕效果的影响。方法：29例TU不起反应者和34例起反应者分别作为试验组和对照组，应用PCR和DNA测序技术对两组外周血标本进行CAG重复数测定，分析该微卫星多态性对激素避孕效果的影响。结果：试验组和对照组CAG重复数的均数分别为23．62和22．97，均数比较差异无显著性（P〉0．05）。短组CAG（n≤22）在试验组和对照组的分布分别为51．7％、50．0％；长组CAG（n〉22）在试验组和对照组分布分别为48．3％、50．0％，长短组分布相同。CAG重复数与精子密度之间未见相关性。在FSH浓度〉0．2IU／L组中，CAG重复数〉22的受试者达到无精子症的机会是其他受试者的1．5倍。结论：受试者AR基因（CAG）n重复数呈多态性，但不反应组与反应组之间不具有显著性差异，AR基因CAG重复数或其他因素与男性激素避孕效果之间的关系有待进一步探讨。     

雄激素受体基因CAG多态性对男性激素避孕有效性影响的研究

目的:分析应用肌注十一酸睾酮酯(TU)进行激素避孕的男性志愿者中起反应者与不起反应者雄激素受体(AR)基因(CAG)n微卫星多态性,并探讨该多态性对激素避孕效果的影响。方法:29例TU不起反应者和34例起反应者分别作为试验组和对照组,应用PCR和DNA测序技术对两组外周血标本进行CAG重复数测定,分析该微卫星多态性对激素避孕效果的影响。结果:试验组和对照组CAG重复数的均数分别为23.62和22.97,均数比较差异无显著性(P>0.05)。短组CAG(n≤22)在试验组和对照组的分布分别为51.7%、50.0%;长组CAG(n>22)在试验组和对照组分布分别为48.3%、50.0%,长短组分布相同。CAG重复数与精子密度之间未见相关性。在FSH浓度>0.2IU/L组中,CAG重复数>22的受试者达到无精子症的机会是其他受试者的1.5倍。结论:受试者AR基因(CAG)n重复数呈多态性,但不反应组与反应组之间不具有显著性差异,AR基因CAG重复数或其他因素与男性激素避孕效果之间的关系有待进一步探讨。     

雄激素受体基因CAG多态性和泌尿系疾病

雄激素受体 (ＡｎｄｒｏｇｅｎＲｅｃｅｐｔｏｒ,ＡＲ)基因对相应靶基因的调控作用已是众所周知。ＡＲ基因和启动子以及可能的加强子的结合导致了相应靶基因的转录 ,因此ＡＲ基因又被称之为转录因子。而ＡＲ基因的转录活性和ＡＲ基因编码谷胺酰胺 (ＣＡＧ)多态性有关。已有报道显示ＡＲ基因ＣＡＧ多态性同前列腺疾病和精子数的高低有关 ,结合笔者的研究 ,在这里作一综述。一、雄激素受体 (ＡＲ)ＡＲ系核受体家族的一员。这个家庭主要包括类固醇激素受体 ,甲状腺激素受体 ,维生素Ｄ受体和视网膜样受体。它可以进一步在顺序同源性的基础上分成…     

中国特发性无精子症和少精子症患者雄激素受体基因CAG重复多态性研究

目的分析中国特发性无精子症和少精子症患者雄激素受体(AR)基因(CAG)n微卫星多态性并探讨该多态性与精子生成障碍发生的关系。方法应用PCR和变性聚丙烯酰胺凝胶电泳分析技术对52例少精子症患者和31例无精子症患者的外周血标本进行CAG重复数测定,分析该微卫星多态性和精子生成障碍发生的关系。结果少精子症患者组和无精子症患者组CAG重复数均数分别为22.19和22.13,CAG重复数≥28的百分率分别为1.9%和3.2%,比例逐渐升高。结论AR基因(CAG)n微卫星的CAG重复数在中国男性不育患者中呈现多态性,与精子生成障碍发生的关系有待进一步研究。     

迟发性性腺功能减退症的研究现状

一、历史背景 男子在50岁以后会出现体能下降、精神神经症状和性功能减退等3方面的临床症状,1939年Werner[1]提出了男性更年期综合征(male climacteric)这个名称.在此后的半个世纪内,人们认为其命名有所不妥,对男性更年期的定义一直存在争论,原因是男性的雄激素水平随着年龄增长的下降过程是逐渐的,没有女性那样出现突然的雌激素水平下降,即使年龄很大多数男子体内仍然存在有一定量的睾酮水平.     

浙江省一农村社区迟发性性腺功能减退症的调查研究

目的:调查乡村中老年男性迟发性性腺功能减退症(LOH)的流行病学情况。方法:2012年4～10月在浙江省嘉兴市嘉善县魏塘乡村采用年龄分层抽样选取996例40～80岁的中老年男性进行中老年男子雄激素缺乏(ADAM)、老年男子症状(AMS)和国际勃起功能问卷-5(IIEF-5)调查,同时测定血清中总睾酮(TT)、性激素结合球蛋白(SHBG)及白蛋白(ALB)水平,Vermeulen公式计算游离睾酮(cFT)及生物可利用睾酮(Bio-T)水平,超声检测前列腺、睾丸体积。结果:研究对象年龄(56.22±8.82)岁,ADAM及AMS筛查LOH的患病率分别为62.86%和23.05%;ED阳性率为68.83%,SHBG、LH、cFT及Bio-T筛查LOH各组之间存在统计学差异。结论:浙江省嘉善县魏塘乡村中老年男性LOH筛查率较国内其他报告(特别是大中城市)LOH筛查率低,ED患病率接近。城乡中老年LOH患病率有差别,值得进一步研究。     

雄激素受体基因ＣＡＧ多态性与前列腺癌的关系

目的：进一步探讨雄激素受体（ＡＲ)基因ＣＡＧ多态性与前列腺癌的关系,方法：采用分子生物学方法对３５８例前列腺癌患者ＡＲ基因ＣＡＧ进行测试,分析ＣＡＧ长度与临床各种指标的关系,结果：经统计学分析显示ＡＲ基因ＣＡＧ与年龄之间呈高相关性（Ｐ＝０．００７,r＝０．１１４）,但与ＰＳＡ、肿瘤分级及分期无显著相关性,结论：ＡＲ基因ＣＡＧ的长度与患者年龄成正比,即前列腺癌患者年龄越轻,其ＣＡＧ长度越短。     

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。     

迟发性性腺功能减退症筛查量表的临床验证研究

目的:探究基于我国社区人口资料的迟发性性腺功能减退症(LOH)患病率以及ADAM问卷和AMS量表(分别简称ADAM和AMS)在我国人群的敏感性、特异性及适用性。方法:1498例中老年健康男性研究对象填写了ADAM和AMS,其中434例进行了生殖激素浓度测定,利用血清总睾酮(tT)和计算的游离睾酮(fT)切点计算LOH的筛查阳性率、雄激素水平低下率、LOH临床患病率、筛查量表的敏感性和特异性等。利用ROC曲线优选AMS评分症状评价的切点值。结果:研究对象中仅有5例曾经不规范地补充过雄激素,调查时没有研究对象补充或主动寻求激素治疗。利用ADAM或AMS筛查40～69岁人群,LOH的平均筛查阳性率分别为80.77%和32.34%;以tT或fT为切点计算出的40～69岁人群平均雄激素水平低下率分别为14.02%和43.69%,ADAM阳性或者AMS阳性研究对象的平均LOH临床患病率分别为37.85%和15.42%;使用fT切点评定的ADAM、AMS的敏感性分别为86.63%和35.29%,特异性分别为24.48%和63.49%。ROC曲线优选的AMS评分症状评价的切点值为19.5分。结论:基于我国人群的ADAM、AMS的敏感性、特异性与国际上的多数研究结论基本一致,LOH筛查阳性率、雄激素水平低下率和临床患病率则明显高于其他研究报道。对于我国人群来说,两个筛查量表具有较好的适用性;ADAM敏感性高,省时、易操作,可作为筛查量表使用,而AMS可作为疗效监测量表使用。     

雄激素受体CAG重复多态性与BPH和PCa相关性的meta分析

目的:通过meta分析探讨雄激素受体(AR)基因CAG重复多态性与良性前列腺增生(BPH)和前列腺癌(PCa)发病风险的关系。方法:检索国内外大型数据库发表的AR基因CAG重复多态性与BPH和PCa相关性的文献,基于异质性检验的结果,分别采用M-H固定效应模型和随机效应模型合并比值比(OR)效应量,采用Begg和Egger偏倚分析评估本项meta分析的发表偏倚,系统评价AR基因CAG重复多态性与BPH和PCa发病风险的关系,并按种族进行分层分析。结果:检索获得文献29篇,最终纳入4篇符合条件的文献,累计BPH患者485例、PCa患者767例、正常对照组709例。BPH组和正常对照组间不存在异质性,M-H固定效应模型合并效应量后提示低CAG重复多态性与BPH无相关性。PCa组和BPH组及对照组间均存在异质性,随机效应模型提示低CAG重复多态性与PCa的风险呈正相关(OR PCa/对照=1.45,OR PCa/BPH=1.86,OR PCa/(BPH+对照)=1.66)。种族分层的亚组分析提示,低CAG重复多态性与PCa发病风险在种族间存在差异。Begg和Egger偏倚分析显示各组比较中均无显著发表偏倚。结论:AR受体低CAG重复多态性与PCa发病风险呈正相关,与BPH发病风险无相关性。     

他达拉非对中老年男性LOH患者T、IIEF及SEP影响的临床研究

目的:观察他达拉非联合安特尔治疗中老年男性迟发性性腺功能低下(LOH)的临床疗效。方法:选择125例中老年男性LOH患者随机分为两组,治疗组65例使用他达拉非加十一酸睾酮治疗,对照组60例使用十一酸睾酮胶囊治疗。分别记录治疗前及治疗后4周时的总睾酮(T)、国际勃起功能指数评分(IIEF)、患者性生活日记(SEP)等的变化。结果:治疗后2组T、IIEF及SEP评分均有不同程度改善,与治疗前比较,差异均有统计学意义(P<0.05);治疗组T、IIEF及SEP评分改善更为显著,与对照组比较,差异均有统计学意义(P<0.05)。结论:使用他达拉非联合十一酸睾酮胶囊,可较好地改善中老年男性患者T、IIEF及SEP分数,提高患者性生活满意度及自信心,具有比单纯补充睾酮更好的综合疗效。     

新疆维吾尔族人群雄激素受体基因CAG重复多态性与良性前列腺增生的关系

目的　初步探讨雄激素受体 (AR)基因CAG重复多态性与良性前列腺增生 (BPH)的关系。　方法　收集 80例维吾尔族BPH患者和 4 0例健康者外周血标本 ,应用PCR和直接测序法行AR基因CAG重复长度测定。分析评价CAG重复长度与BPH的关系。　结果　BPH组CAG重复次数范围 13～ 30 ,平均 2 2 .78。对照组CAG重复次数范围 14～ 2 9,平均 2 2 .38。两组比较差异无显著性意义 (P >0 .0 5 )。CAG重复长度 <2 2和≥ 2 2比较 ,其OR值为 1.0 6 (95 %CI 0 .4 6～ 2 .4 8,P >0 .0 5 )。CAG重复长度与BPH患者年龄 (γ =- 0 .0 6 ,P >0 .0 5 )、国际前列腺症状评分 (IPSS) (γ =0 .11,P >0 .0 5 )无相关性 ,而与前列腺的体积相关 (γ =- 0 .2 6 ,P <0 .0 5 )。在BPH患者 ,前列腺体积随着CAG重复次数的增加而减小 ,差异有显著性意义 (趋势检验P <0 .0 5 ) ,CAG重复长度≤ 2 0与≥ 2 5相比 ,前列腺体积差异有显著性意义 (P =0 .0 5 )。　结论　AR基因CAG重复长度与BPH腺体的增长有关。     

Androgen receptor gene CAG repeat polymorphism and breast cancer risk in Iranian women: a case-control study

We investigated the association between polymorphic expansion of trinucleotide CAG repeats in androgen receptor (AR) gene and breast cancer risk among Iranian women in a matched case-control study. There was a strong overall association between per CAG repeat increments in average repeat length and the risk of the malignancy [OR=3.56; 95% CI, 2.80-5.29]. Women carrying one or two alleles with [CAG]n repeat ≥22 units were at increased risk of breast cancer [OR=2.03; 95% CI, 1.56-2.6]. The risk was significantly increased in homozygous longer repeats, versus homozygous alleles <22. We observed reduced risk of developing the tumor in positive familial breast cancer subjects carrying repeats ≥22 and 23. Homozygosity for the longer [CAG]n repeats may be linked to the increased breast cancer risk. In contrast to previous reports, longer AR [CAG]n repeat alleles may decline the risk among women with a familial breast cancer.     

Survey for late-onset hypogonadism among old and 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>0.05); 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.     

The polymorphic androgen receptor gene CAG repeat,pituitary-testicular function and andropausal symptoms in ageing men

The activity of androgen receptor (AR) is modulated by a polymorphic CAG trinucleotide repeat in the AR gene. In the present study, we investigated hormonal changes among ageing men, and whether the number of AR CAG triplets is related to the appearance of these changes, as well as symptoms and diseases associated with ageing. A total of 213 41-70-year-old men donated blood for hormone analyses (LH, testosterone, oestradiol and SHBG) and answered questions concerning diseases and symptoms associated with ageing and/or androgen deficiency. Of these men, 172 donated blood for the measurement of the CAG repeat length of AR. The CAG repeat region of the AR gene was amplified by polymerase chain reaction (PCR) and the products were sized on polyacrylamide gels. The repeat number was analysed as a dichotomized variable divided according to cut-off limits of the lowest (< or =20 repeats) and the highest quartile (> or =23 repeats), and as a continuous variable. The proportion of men with serum LH in the uppermost quartile (>6.0 IU/L) with normal serum testosterone (>9.8 nmol/L, above the lowest 10%) increased significantly with age (p = 0.01). There were fewer men with this hormonal condition among those with CAG repeat number in the uppermost quartile (> or =23 repeats) (p = 0.03). These men also reported less decreased potency (p < 0.05). The repeat number was positively correlated with depression, as expressed by the wish to be dead (r = 0.45; p < 0.0001), depressed mood (r = 0.23; p = 0.003), anxiety (r = 0.15; p < 0.05), deterioration of general well-being (r = 0.22; p = 0.004), as well as decreased beard growth (r = 0.49; p < 0.0001). A hormonal condition where serum testosterone is normal but LH increased is a frequent finding in male ageing. Only certain types of age-related changes in ageing men were associated with the length of the AR gene CAG repeat, suggesting that this parameter may play a role in setting different thresholds for the array of androgen actions in the male.     

Molecular analysis of CAG repeat length of the androgen receptor gene and Y chromosome microdeletions among Jordanian azoospermic infertile males

Assisted reproductive technology is a common procedure which helps millions of couples who suffer fertility problems worldwide every year. Screening for genetic abnormalities prior to such procedure is very important to prevent the transmission of harmful genetic mutations to future generations. Microdeletions within the azoospermia factor (AZF) region of the Y chromosome and the expansion of the CAG trinucleotides in the androgen receptor (AR) gene are among the susceptible causes of male infertility in different ethnic groups. Such association has never been studied in Jordan. In this study, we compared CAG repeat length between azoospermic infertile and normospermic fertile Jordanian males and we also screened the frequency of Y chromosome microdeletions in the same cohort. The study included 142 nonobstructive azoospermic cases and 145 normospermic controls. Results have shown that the median CAG repeat length in the azoospermic group is 19 ± 2 compared to 19 ± 1.5 (p = .6262) in the control group. Deletions within the Y chromosome AZF region were detected in 7 of 142 cases (4.93%) and no deletions were seen in the control group. The results of this study confirm the importance of the AZF region in normal spermatogenesis, whereas it shows no link between the length of CAG repeats in the AR gene and male azoospermia in Jordanian group examined.     

AR CAG repeat length is not associated with serum gonadal steroids and lipid levels in healthy men

Cardiovascular risk factors seem to be affected by androgens, which exert their action through the androgen receptor (AR). Androgenic action correlates inversely with a polymorphic CAG repeat region in the AR gene encoding for glutamine residues the length of which appears to influence high density lipoprotein (HDL) cholesterol levels. The aim of the study was to investigate the possible association between AR gene polymorphism and serum sex steroids and lipids. 170 healthy males, aged 22–59 years (mean 42 years), were included in the study. Anthropometrical as well as sociometrical parameters were recorded. Body fat content (BFC) (% fat mass) was measured by bioelectrical impedance. Serum lipids and total and free testosterone (T) and estradiol (E₂) levels were measured in each subject. AR gene CAG repeats length was determined. No significant correlation was found between the length of AR gene polyglutamine tract and the levels of gonadal steroids (total and free T, total and free E₂) or to the lipid levels (Triglycerides, total, HDL and LDL cholesterol). In addition, serum lipid levels were not significantly different in the lower compared to higher half of CAG repeats length distribution. On multiple regression analysis BFC was found to predict HDL-cholesterol and triglycerides were found to show, respectively, significant negative and positive correlation with body fat content. In conclusion, AR gene polymorphism may not predict sex steroid levels in healthy males. Possible impact of CAG repeats length on lipids profile has not been established.