何谓男人? 睾酮(T) 及其衍生物双氢睾酮(DHT) 正常及Klinefelter 综合征睾丸病理* 克氏综合征Klinefelter Syndrome 诊断要点1.典型体征：睾丸细小，容积小于3 ml，质硬，身材修长，下肢长，第二性征不发育或发育差，皮肤细腻，乳房女性化，阴茎短小2. 智力发育迟缓，性格和行为异常表现，精神障碍3.性功能异常及不育。4.睾丸活检:曲细精管玻璃样变性。5.染色体核型多表现为47 XXY 或46 XY/47XXY 嵌合体。6.内分泌检查: FSH 和LH ，T 7.精液检查无精子克氏综合征Klinefelter Syndrome 治疗1.早期心理治疗及特殊教育2.青春期前期药物治疗：最佳年龄11～12岁，尽管无助于生育，可促使学习提高，增强自信心。雄激素的首次剂量50～100 mg, 以后每2～4周增加50～100 mg，直到成人用量，一旦治疗开始，就应维持终身。3.成人药物治疗：可促成男性第二性征发育、改善性功能，改进情绪及行为状况，使肌肉变得健壮，增加骨质密度。而对睾丸大小、生精功能无明显改善，无助改善生育。克氏综合征Klinefelter Syndrome 雄激素替代疗法应监测血清睾酮水平，避免诱发攻击性行为，一般使血清睾酮维持在正常范围；激素治疗一般不影响男子乳房异常发育参考文献1.郭应禄,辛钟成.男子生殖医学.北京:北京医科大学出版社.2002：149-150 2.邓春华, 辛钟成等.男科病诊治学.广州:羊城晚报出版社.2004：262-264 雄激素& 男科疾病雄激素& PADAM 雄激素& ED 雄激素& 不育症雄激素& 克氏综合症雄激素& 前列腺炎雄激素的安全性前列腺炎-- 由于前列腺受到微生物等病原体的感染或某些非感染因素刺激而发生的炎症反应, 及由此造成的患者前列腺区域不适或疼痛, 排尿异常, 尿道异常分泌物等临床表现, 是一种常见且让人十分困惑的疾病. 慢性前列腺炎慢性前列腺炎前列腺炎时, 前列腺液中锌浓度降低, 影响精子活力ACP( 酸性磷酸酶) 的合成和分泌受雄激素的调控, 蛋白酶系被激活, 使精液液化, ( 慢性前列腺炎时其分泌活动减低, 精液不液化发生率明显升高) 特点心里负担过重惧怕性生活体内雄激素水平下降久治不愈ED 症状PADAM 症状雄激素的适用症及用法(1) 前列腺分泌液较少的; 及干性前列腺液患者: 理由: 前列腺液量的多少可以影响其代谢。雄激素促进前列腺液的分泌。效果：前列腺液分泌量增加；较易获取前列腺液。葛秦生主编《临床生殖内分泌学》雄激素的适用症及用法(2) 精液不液化或液化迟缓病因：液化因子与凝固因子平衡失调. 理由: 精液不液化与雄激素水平低下有关精液的产生直接受睾酮的控制。效果：液化改善雄激素的适用症及用法(3) 慢性前列腺炎患者伴有不育 理由：雄激素制剂在男性不育症合并睾丸发育不良及雄激素水平低下的患者中是明确的治疗应用适应症特发性少弱精症：精浆果糖浓度低下精子质量不好，活力弱畸精症，精液内有大量生殖细胞脱落精液质量异常雄激素& 男科疾病雄激素& PADAM 雄激素& ED 雄激素& 不育症雄激素& 克氏综合症雄激素& 前列腺炎雄激素的安全性尿流量( ml / 秒) 年Gooren, J Androl 1994; 15: 212 ~5 正常范围口服十一酸睾酮10 年安全性研究( 性腺功能低下病人的尿流量变化) 睾酮对前列腺的作用 TU 160 mg/d ，12 个月，老年性腺机能低下男子PSA 水平的变化(ng/L) 国际前列腺评分的变化(IPSS) Andriol (N=39) Andriol (N=39) Placebo (N=37) Placebo (N=37) N.S.P = 0.47 Wittert et al. J Gerontol 2003;58A:618-625 N.S.P = 0.25 安特尔对前列腺的影响 十一酸睾酮160 毫克/ 天治疗中年男性8 个月Holm ng et al. Prostate 1993;23:99-106 尿流量峰值(mL/sec) 尿量(mL) * p<0.01 vs 治疗前* * 睾酮治疗PADAM 对前列腺的作用睾酮治疗试验中老年男子前列腺癌的发生率在相关的*睾酮治疗研究中，在8,501 个治疗月中有4 例新发生的前列腺癌( 约1 per 177 man-years), 在3,228 个对照月中未报道前列腺癌在Massachusetts Male Aging Study ( 未治疗的老年男子), 在1,576 名男子被随访8 年后，有70 例前列腺癌发生( 约1 per 180 man-years) Mohr et al. Urology 2001;57:930-935 * 3 months treatment in 10 aging males and active prostate monitoring TRT 和前列腺癌Rhoden & Morgentaler review. NEJM.2003M. Algarte-Genin et al. European Urology. 2004  	 	 Rhoden & Morgentaler: 	“There appears to be no compelling evidence at present to suggest that men with higher testosterone levels are at greater risk of prostate cancer or that treating men who have hypogonadism with exogenous androgen increases this risk” 目前没有证据表明，内源性睾酮水平较高、或使用外源性雄激素治疗的男性发生前列腺癌的风险会增加。结论小结: 雄激素在男科的应用PADAM: 全面改善症状ED: 不仅仅是改善性欲不育: 有利于精子活力改善(?) 克氏综合症：有助于男性第二性征发育慢性前列腺炎: 改善精液液化状态(?) 谢谢!! 谢谢！* 睾酮在体内作用于不同的靶器官, 产生不同的生理作用. 正是由于睾酮具有如此多的靶器官及生理功能, 如临床上发生睾酮缺乏, 就会产生大量的症状. * 强调: 男子更年期的临床表现不仅是性功能方面的症状, 还有其他许多方面, 例如: 精神心理症状, 生理体能症状及血管舒缩症状. 调查显示: 男子更年期的临床表现中, 18%的表现为骨及关节痛, 40%表现为各种各样的精神心理症状, 30%为躯体体能症状, 性功能障碍的表现仅为6 ~ 8%. * * * 先生们、女士们，这里做一下最后的总结，第一，越来越多的文献证明了中老年男性性腺功能减退其生活质量会受到明显的影响这一观点。第二，患者通常会无视、医生通常会忽视对性腺功能减退的认知、评估与治疗，应该通过对患者适当的问诊、适当的体检来辨别是否有性腺功能减退的症状和体征，并且通过生化检查测定睾酮浓度来确诊。同样，有充分的依据支持这一观点：这些患者在接受了适当的睾酮补充治疗后，其迟发性性腺功能减退症状会得到明显缓解。* NOTES An increased incidence of erectile dysfunction has been reported with aging. Longitudinal results from the Massachusetts Male Aging Study, where 1156 men between 40 and 69 years with an average follow-up of 8.8 years, a have show that the annual incidence rate increased from 12 cases (40-49 years) to 46 cases (60-69 years) per 1000 man-years. Erectile dysfunction was associated with lower education, diabetes, heart disease and hypertension1. The etiology of erectile dysfunction in aging men is usually multifactorial1-3, and late-onset hypogonadism is a contributing factor in a minor part (8-15%) of cases3,4. There is a relationship between testosterone level and frequency, duration and degree of spontaneous erections occurring during sleep5. Although some studies found no relationship with testosterone levels in older men6,7, three other studies reported lower testosterone levels in patients with erectile dysfunction than in age-matched, healthy controls (p<0.05)2,3,8 References 1. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40-69 years old: longitudinal results from the Massachusetts Male Aging Study. J Urol 2000;163:460-4632. Jannini EA, Screponi E, Carosa E, Pepe M, Lo Giudice F, Trimarchi F, Benvenga S. Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone. Int J Androl 1999;22:385-3923. Kaiser FE, Viosca SP, Morley JE, Mooradian AD, Stanik Davis S, Korenman SG. Impotence and aging: clinical and hormonal factors. J Am Geriatr Soc 1988;36:511-5194. Buvat J, Lemaire A. Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy. J Urol 1997;158:1764-17675. Granata ARM, Rochira V, Lerchl A, Marrama P, Carani C. Relationship between sleep-related erections and testosterone levels in men. J Androl 1997;18:522-5276. Korenman SG, Morley JE, Mooradian AD, Stanik Davis S, Kaiser FE, Silver AJ, Viosca SP, Garza D. Secondary hypogonadism in older men: its relation to impotence. J Clin Endocrinol Metab 1990;71:963-9697. Rhoden EL, Tel ken C, Sogari PR, Vargas Souto CA. The relationship of serum testosterone to erectile function in normal aging men. J Urol 2002;167:1745-17488. Ahn HS, Park CM, Lee SW. The clinical relevance of sex hormone levels and sexual activity in the aging male. Br J Urol Int 2002;89:526-530 * Historically,it has been always recognized that androgens play in maintaining sexual activity was thought to be via it role mainly on sexual interest. But with accumulating evidence both animals and humans to androgen’s local effects: Animal studies showed that expression of nitric oxide synthase (NOS) gene inside the penis depends on the presence of adequate androgen levels (Penson et al. 1996, Mills & Lewis 1999; mills et al. 1999) Castration may also affect PDE5 gene expression (Traish et al. 1999) In humans, it has been observed that the efficacy of erectile dysfunction (ED) therapy with PDE5 inhibitors (PDE5i) may be blunted in patients with subclinical hypogonadism in whom androgen levels have not been previously normalized (Guay et al. 2001) In general, evidence indicate that testosterone is involved in the maintenance of sexual activity at multiple sites (Anderson et al. 1992) and that adequate blood testosterone concentration are necessary to keep intact molecular machinery of penile