GnRH脉冲泵治疗难治性低促性腺激素性男性不育4例报道

本文报道GnRH脉冲泵输注戈那瑞林治疗经双促性腺激素诱导精子失败后的低促性腺激素性男性不育患者的临床效果并文献回顾。4例患者均以低促性腺激素性性腺功能减退性不育为主要表现,均曾经过双促性腺激素(HCG+HMG)治疗7~18个月,未成功诱导出精子,改用GnRH脉冲泵输注戈那瑞林治疗2~7个月,促性腺激素和性激素水平明显上升,雄激素缺乏症状显著改善,4例患者均有精子生成,1例患者配偶自然妊娠,1例患者人工授精妊娠,2例期待自然妊娠或人工助孕。通过本文病例分析和复习文献资料发现,GnRH脉冲泵输注戈那瑞林不仅是低促性腺激素性性腺功能减退男性不育的有效治疗方法,还可以作为促性腺激素诱导精子失败后的补充疗法。     

促性腺激素释放激素及其类似物的研究进展

促性腺激素释放激素 (GnRH) ,是由下丘脑分泌的十肽激素 ,其受体为钙离子动员受体。GnRH脉冲式释放刺激垂体促性腺激素的合成和分泌从而调节性激素的分泌 ,是性腺轴系的原动力 ,此外对性腺还可能具有直接作用。对GnRH分子结构修饰而合成的结构类似物 ,已经在生殖内分泌疾病治疗、计划生育等方面得到应用。     

特发性低促性腺激素性性腺功能减退症不同治疗方案的研究进展

特发性低促性腺激素性性腺功能减退症(IHH)是临床上逐渐被认识的发育异常疾病,随着医学的不断发展,其治疗方法也逐渐趋于规范.对于IHH的治疗,男性的目前治疗方案主要包括睾酮替代、促性腺激素治疗和GnRH脉冲治疗.这三种方案可根据患者年龄、生活状态和需求进行选择,并可互相切换.女性在无生育需求时,予周期性雌、孕激素联合替...     

评价各种控制性卵巢刺激方案中垂体的功能状态

一、正常月经周期中下丘脑-垂体-卵巢的调节垂体促性腺激素细胞同时分泌黄体生成素(LH)和卵泡刺激素(FSH),对下丘脑分泌的促性腺激素释放激素(GnRH)脉冲性释放产生反应.GnRH系统是促进促性腺激素(Gn)的原发性机制,下丘脑的其他肽类激素[催产素、促肾上腺皮质激素释放因子(CRF)、神经肽Y、肝丙肽]直接或间接的影响FSH和LH的分泌.     

HCG、FSH联合治疗低促性腺激素性性腺功能减退症29例报告

目的 探讨人绒毛膜促性腺激素(HCG)和促卵泡激素(FSH)联合治疗男性低促性腺激素性性腺功能减退症的有效性和安全性.方法 29例男性低促性腺激素性性腺功能减退症23例,Kallmann综合征6例.治疗方案:采用联合HCG 2000 IU,2次/周;FSH 75 IU,3次/周,肌肉注射,连续用药至少3个月. 结果治疗后所有患者体力改善,体质增强;22例患者出现胡须、阴毛和(或)腋毛.睾丸体积治疗前(2.68±1.44)ml,治疗后(8.93±3.24)ml(P<0.01);促卵泡激素(FSH)、促黄体激素(LH)和睾酮(T)水平有所提高(P<0.05);12例患者出现遗精现象,8例有精子生成.结论 对男性低促性腺激素性性腺功能减退症,用HCG和FSH治疗能促进青春期第二性征发育,并可使部分睾丸恢复产生雄激素和生成精子功能.     

GnRH的功能、作用机制及其在肿瘤治疗中的应用

促性腺激素释放激素 (gonadotropin releasinghormone ,GnRH ) ,以前也称LHRH ,促黄体激素生成激素 ,是一种由脑组织分泌以调控生殖系统功能的信号分子。GnRH10肽小分子由下丘脑的神经内分泌细胞分泌入门静脉系统 ,随血流进入垂体 ,在那里刺激垂体细胞分泌黄体生成激素 (luteininghormone ,LH)和卵泡刺激激素 (follicle stimulatinghormone ,FSH)。它必须与高亲和力的跨膜受体结合才能发挥作用 ,这些跨膜受体属于七次跨膜受体家族[1] 。促性腺激素依次调控配子的形成和性腺的内分泌功能。近来 ,在中枢神经系统和周围组织中也发现了Gn…     

降调节COS方案中的卵泡发育不同步

1988年Palermo等[1]第一次在12例反复控制性卵巢刺激(COS)失败的妇女采用黄体期短效促性腺激素释放激素激动剂(GnRH-a)长方案(500～600 ug/d喷鼻)联合促性腺激素(Gn)治疗获得多卵泡发育,获卵数由(3.2±0.1)个增加到(8.0±0.3)个.由此提出GnRH-a给药早期的垂体激发作用有利于血清黄体生成素(LH)和卵泡刺激素(FSH)水平升高、增加卵泡募集,促进卵泡发育的同步化.     

精子发生的内分泌激素调节

下丘脑-垂体-睾丸轴系对男性生殖功能起着关键性作用,精子发生是这个轴系精密调节的结果。下丘脑促性腺激素释放激素(GnRH)脉冲式释放控制了卵泡刺激素(FSH)和黄体生成素(LH)的波动性分泌,GnRH脉冲频率的变化调节垂体促性腺细胞分泌两种不同的激素,是一种独具一格的机制。促性腺激素抑制激素(GnIH)于2000年首次从鹌鹑垂体鉴定出来。GnIH的发现使我们更深入地了解下丘脑激素对垂体促性腺细胞的调节。哺乳动物的GnIH神经元定位于下丘脑背内侧核,轴突延伸至正中隆突。GnIH通过其受体GPR147抑制垂体促性腺细胞的功能。成年男子的精子发生需要FSH和睾酮的共同作用,任何二者之一缺失会损害Sertoli细胞的分化和功能以及生精细胞在精子发生过程的发育。睾酮至少从4个方面促进精子发生:(1)紧密连接(tight junction)的形成和功能;(2)附睾的发育和功能;(3)生精细胞的发育;(4)精子释放。在体研究提示,雌激素亦对精子发生起重要作用,雌二醇调节小鼠精原细胞系和精母细胞系调亡和抗调亡之间的平衡。     

LHRH对灌流的雄性大鼠垂体细胞分泌LH的自身激发作用

为了研究LHRH(促黄体激素释放激素)对雄性大鼠垂体细胞分泌LH(促黄体激素)是否有自身激发作用,我们用不同幅度(1×10~(-10)～1×10~(-8) mol/L)和不同频率(1～4脉冲/小时)的LHRH脉冲刺激灌流的SD雄性大鼠垂体前叶细胞,观察了在灌流系统中细胞LH的分泌反应。结果表明,在高幅度(1×10~(-9)mol/L或更大)和高频率(3脉冲或更高)LHRH脉冲作用下,灌流的垂体细胞可表现自身激发作用,即在LHRH刺激一定时间后,同样的LHRH刺激产生更大的LH释放。但是,低幅度(1×10~(10)mol/L)LHRH即使在高频率下也不能显著地改变LH反应性。上述实验说明:离体成年雄性大鼠垂体前叶细胞存在对LHRH的自身激发作用,这种自身激发作用的产生主要依赖于LHRH脉冲的幅度和频率。     

促性腺激素对于下丘脑-垂体性闭经不育患者助孕治疗的疗效观察

目的总结下丘脑-垂体性闭经不育患者进行辅助生育治疗的结局及治疗特点。方法收集2001年2月至2009年2月在北京协和医院辅助生育中心行助孕治疗的76例下丘脑-垂体性闭经患者的临床资料,回顾性分析促性腺激素刺激卵巢进行诱导排卵或行体外受精(IVF)的反应性及治疗结局。结果 76例患者共进行了136个促性腺激素刺激卵巢周期(诱导排卵周期127个,IVF周期9个)。总有效治疗周期124个(有效的诱导排卵周期115个,IVF周期9个),因各种原因取消的周期12个,诱导排卵的有效率90.55%(115/127)。生化妊娠周期1个,临床妊娠周期57个,每个有效治疗周期的临床妊娠率为45.97%(57/124)。76例患者中,73例获得了有效治疗周期,共有53例临床妊娠,患者的累计妊娠率为72.6%(53/73);40例患者在第1个有效治疗周期即成功妊娠,即第一个治疗周期的妊娠率为54.8%(40/73)。结论应用外源性促性腺激素是治疗下丘脑-垂体原因无排卵不育的有效方法,可获得较好的排卵率和妊娠结局。     

Change of serum adrenal androgens in prostatic cancer patients after bilateral orchidectomy or LHRH agonist treatment

Bilateral orchidectomy (ORX) or administration of luteinizing hormone releasing hormone agonist (LHRH) for prostatic cancer patients causes suppression of testicular androgens. However, the suppression of adrenal androgens by these treatments is controversial. We measured serum concentrations of testosterone (T), 4-androstene-3, 17-dione (A-dione), dehydroepiandrosterone (DHEA), LH, follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) and cortisol before and after 3-12 months of the first hormonal treatment in 17 prostatic cancer patients who had received ORX (8 cases) or LHRH (9 cases). ORX and LHRH decreased serum T to the castration level significantly (ORX: p < 0.001, LHRH: p < 0.0001). ORX increased serum LH and FSH significantly (LH: p < 0.001, FSH: p < 0.001), whereas LHRH decreased LH and FSH significantly (LH: p < 0.05, FSH: p < 0.05). Neither treatment caused any significant change in ACTH or cortisol. ORX and LHRH decreased the serum A-dione significantly (ORX: p < 0.01, LHRH: p < 0.001). LHRH decreased the serum DHEA significantly (p < 0.01), whereas ORX did not decrease serum DHEA. These data suggest that "medical" and "surgical" castration, especially LHRH agonist, may decrease not only testicular androgens but also adrenal androgens.     

碱性成纤维细胞生长因子用于治疗特发性少弱精子症的临床意义(附57例疗效观察)

为了探讨碱性成纤维细胞生长因子（ｂＦＧＦ）对特发性少弱精子症患者的作用,本研究对５７例确诊为将发性少弱精子症的患者用ｂＦＧＦ治疗,分别在治疗前后进行血生殖激素测定和精液质量分析。结果发现治疗后血生殖激素（ＰＲＬ、ＦＳＨ、ＬＨ、Ｔ）水平升高,精子密度及顶体酶活性显著提高（Ｐ〈０．０１）,精子活动力和成活率上升、畸形率下降（Ｐ〈０．０５）,生育能力提高。因此认为ｂＦＧＦ是治疗特发性少弱精子症的有效药物。     

The physiological significance of pulsatile LHRH secretion in man: gonadotrophin responses to physiological doses of pulsatile versus continuous LHRH administration

This study tested whether pulsatile LHRH stimulation of the pituitary is required for normal gonadotrophin secretion in man. Four men with idiopathic hypogonadotrophic hypogonadism (IHH) and presumed endogenous LHRH deficiency were taken off all hormonal replacement for 5-6 weeks, then 5 micrograms LHRH was administered every 2 h for 1 week in order to prime pituitary gonadotrophin responsiveness. A physiological dose of LHRH (10 micrograms every 2 h) was then administered in both pulsatile and continuous regimens, in varying order, to each man. Pulsatile LHRH was capable of stimulating LH (as measured by bioassay) and FSH secretion, while continuous administration of LHRH was not. Serum LH, measured by RIA and bioassay, and FSH and free alpha-subunit levels, measured by RIA, increased significantly (P less than 0.05) over pretreatment levels during pulsatile LHRH administration. In contrast, bioactive LH and immunoactive FSH did not change significantly compared to pretreatment values during continuous infusion of the same total LHRH dose, although immunoactive LH and free alpha-subunit levels did increase significantly (P less than 0.05). The ratio of LH bioactivity to immunoactivity was significantly lower during the continuous compared to pulsatile LHRH regimen (P less than 0.001). Similar serum LHRH levels were achieved during pulsatile and continuous infusions. Serum testosterone and oestradiol levels did not increase significantly from pretreatment levels during either regimen of LHRH administration. It is concluded that a pulsatile LHRH signal pattern is essential for normal pituitary gonadotrophin secretion in men with IHH. Continuous infusion of a physiological dose of LHRH, which produced serum LHRH levels which were indistinguishable from those found during pulsatile administration, failed to stimulate FSH or bioactive LH secretion.     

MPA和MPA+TU对雄性大鼠生精功能和生殖激素的影响

目的 :观察单独使用醋酸甲孕酮 (MPA)和联合应用MPA与十一酸睾酮 (TU)对雄性大鼠血清FSH、LH、T和生精功能的影响。　方法 :2 0只大鼠随机均分为 4组 :A组为对照组 (给予生理盐水 ) ,B组小剂量MPA组 (37.5mg/kg) ,C组大剂量MPA组 (75mg/kg) ,D组为MPA +TU(MPA 75mg/kg ,TU 2 5mg/kg) ,肌肉注射 ,每月 1次 ,共 3个月。测定各组大鼠给药前后血清FSH、LH、T水平及各组大鼠精子计数和形态。　结果 :与对照组相比 ,处理组大鼠生精功能均明显受到抑制 ;单用MPA组的FSH、LH水平均显著降低 ;MPA +TU组的FSH、LH、T水平均明显下降 ,睾丸明显萎缩 ;与单用MPA组相比 ,MPA +TU组精子计数下降更显著 ,但血清FSH和LH受抑制的程度差异无显著性。　结论 :单独使用MPA可以抑制雄性大鼠血清FSH、LH水平并阻抑其生精功能 ;MPA +TU比单用MPA抑制生精效应更强。MPA +TU抑制生精的机制不仅仅在于反馈抑制促性腺激素 ,而且可能对睾丸本身有直接的抑制作用     

Andropause: incidence and pathogenesis

One hundred forty-five male volunteers, 60 to 91 years old, without any hepatic, renal, or metabolic pathology, and not under any steroid therapy for at least 1 year were studied. Plasma luteinizing hormone (LH), Follicle Stimulating hormone (FSH), Testosterone (T), 17-beta-Estradiol (E2), Androstenedione (A), Maximal increase (MI) of LH and FSH after luteinizing hormone releasing hormone (LHRH) (50 gamma iv), and pulsations (P) of LH and FSH over a 3 hr period were measured by radioimmunoassay (RIA). The patients were divided in four groups according to LH and T levels. Group I: (46% of our subjects) showed no signs of hypogonadism with normal LH, T, E2, A, MI of LH and FSH, and normal P-LH, P-FSH. Group II: (15%) with high LH but normal T, showed high FSH, MI-LH, MI-FSH, P-LH, and P-FSH, but normal A and E2. Group III: (22%) with classical signs of hypergonadotropic hypogonadism (high LH and low T) showed high FSH, MI-LH, MI-FSH, and P-FSH, normal P-LH and E2, but low A. Group IV: (16.5%) with signs of hypogonadotropic hypogonadism (low LH and low T) had also low MI-LH, MI-FSH and A, but normal FSH, P-LH, P-FSH, and E2. Contrarily to menopause in women, andropause is not an obligatory event in men, and when it does occur, its pathogenesis and hormonal aspects are very variable.     

醋酸棉酚对男子垂体－性腺轴功能的影响

报道２２例长期停服棉酚男子性激素的水平及其对ＬＨＲＨ和ｈＣＧ刺激的反应。２２例中，１１例生精功能未恢复者（无精子症组）的ＦＳＨ和ＬＨ基础值及其对ＬＨＲＨ刺激反应均显著高于正常对照组（１１例），而睾酮（Ｔ）基础值和Ｔ／ＬＨ比值及Ｔ对ｈＣＧ刺激反应显著低于正常对照组。生精功能恢复组（１１例）的ＦＳＨ基础值及其对ＬＨＲＨ刺激在应均显著高于正常对照组。但是，ＬＨ和Ｔ基础值及其对ＬＨＲＨ和ｈＣＧ刺激反应，二者差异不显著。这些结果说明，不适当的棉酚治疗所引起的永久无精子症者，全睾丸细胞受到严重损害，垂体－睾丸轴系功能调节发生紊乱；而适量的棉酚所引起的暂时无精子症，生精功能恢复以后，睾丸内分泌一般均正常     

Recovery of spermatozoa after rFSH/hCG treatment, and subsequent ICSI/IVF, in a male with testicular atrophy due to severe congenital hypogonadotrophic hypogonadism

A 47-year old man attending at an in vitro fertilization clinic for infertility was diagnosed with congenital idiopathic hypogonadotrophic hypogonadism. No palpable testes and no spermatozoa in the ejaculate were found. Endocrinologically serum FSH, LH and testosterone was undetectable. A retroperitoneal magnetic resonance imaging confirmed the testicular absence. rFSH/hCG treatment was initiated. At four months almond-sized testes had developed and puncture with testicular sperm extraction (TESE) showed occasional immobile spermatozoa. Six months after initiation of treatment occasional mobile spermatozoa in semen were successfully used for intracytoplasmic sperm injection (ICSI) and one oocyte was fertilized and transferred. After 12 months sperm count revealed 10(5) mobile spermatozoa and three oocytes were fertilized. The embryo transfers did not result in a clinical pregnancy. As far as we know, this is the first time that objectively diagnosed testes atrophy could be successfully treated with FSH/hCG.     

男性甲亢患者治疗前后血清性激素水平观察

目的:探讨男性甲亢患者治疗前后血清性激素水平的变化及其临床意义。方法:采用化学发光免疫法测定68例男性甲亢患者治疗前后血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)和雌二醇(E2)的水平,并与对照组比较,进行统计学分析。结果:男性甲亢患者治疗前血清T和E2的水平明显高于对照组,差异有显著性(P<0.05);FSH、LH的水平与对照组相比差异无显著性(P>0.05)。男性甲亢患者治疗后血清FSH、LH、T和E2的水平与对照组相比差异无显著性(P>0.05)。结论:男性甲亢患者存在性激素代谢紊乱;患者血清T和E2水平的增高是机体为了适应高代谢环境,下丘脑-垂体-性腺轴所产生的适应性变化;随着甲亢得到控制,其水平恢复正常。     

特发性无精子症与精索静脉曲张无精子症的生殖内分泌及睾丸病理学研究

对特发性无精子症50例、精索静脉曲张无精子症16例及对照57例分别从血FSH、LH和T,睾丸体积,曲细精管直径、管壁厚度、管内上皮及间质病变情况进行了比较。二类无精子症的FSH、LH及T水平无显著差异,但特发性的FSH、精索静脉曲张的LH有较对方升高更多的趋势。二类无精子症的睾丸体积、曲细精管直径及管壁厚度无明显差异,但精索静脉曲张无精子症曲细精管内细胞脱落严重并伴有间质水肿及小血管病变,而特发性无精子症则曲细精管内生精阻滞明显。提示间质病变及有可能继发于之的曲细精管内细胞脱落是精索静脉曲线无精子症有别于特发性无精子症的重要特征。