生殖内分泌相关疾病课件

1、Reproductive Endocrinology Related Diseases生殖内分泌相关疾病Zhejiang University School of Medicine,Womens HospitalWu Ruijin Mechanism of Normal Menses下丘脑垂体卵巢轴(hypothalamic-pituitary-ovarian axis,HPOA)调节和反馈正常卵巢正常（有足够始基卵泡和对Gn正常的反应性）子宫完整，子宫内膜对雌、孕激素有正常反应性下生殖道通畅Amenorrhea闭 经Definitionprimary amenorrhea（原发性闭经）：5%

2、 No period by age 16 regardless of the presence of normal growth and development or the appearance of 2nd sexual characteristics.(16岁，第二性征已发育，尚无月经来潮；) 或 No period by age 14, absence of growth or development of 2nd sexual characteristics;(14岁，无第二性征，无月经来潮)secondary amenorrhea（继发性闭经）：95% No period for

3、a length equivalent to at least 3 x previous cycles intervals or no periods for 6 months. (月经停止6个月，或自身3个周期以上)ClassificationClassicHormonal （1） Gonadotropins （按FSH水平分） 高FSH闭经：血清FSH30IU/L，提示卵巢功能衰退 低FSH闭经： FSH、LH5IU/，提示病变在下丘脑或垂体 （2）Estrogen （按雌激素水平分） 度闭经：子宫内膜已受一定雌激素影响，用孕激素后有撤退性出血（黄体酮试验） 度闭经：体内雌激素水平低落，子

4、宫内膜菲薄或萎缩，用孕激素后不出现撤退性出血 （3）Prolactin：高泌乳素血症“4- Compartment” (按解剖部位分) Outflow tractOvaryAnterior pituitaryHypothalamus 中枢神经-下丘脑垂体卵巢子宫PathogenesisPrimary Amenorrhea (原发性闭经)多由遗传学原因或先天性缺陷引起体内有一定雌激素水平则第二性征发育正常或接近正常体内无雌激素分泌第二性征缺乏Secondary Amenorrhea 继发性闭经1.Hypothalamic amenorrhea 下丘脑性闭经 （55%）：最常见, 功能性为主，Gn

5、RH 脉冲分泌频率、幅度、量的异常均可致闭经。 精神应急性（psychogenic stress） ：创伤、紧张、环境改变 体重下降、神经性厌食（weight loss，anorexia nervosa） 长期 过剧运动 ： 体脂减少 Leptin下降 药物： 可逆性 利血平、氯丙嗪 下丘脑多巴胺 垂体PRL 避孕药 抑制下丘脑GnRH颅咽管瘤： 瘤体压迫垂体柄，下丘脑GnRH和多巴胺运送受抑制Kallmann综合征（嗅觉缺失综合症）下丘脑GnRH先天性分泌缺陷伴有嗅觉丧失或减退低促性腺激素性性腺功能减退原发闭经、无性征发育、内生殖器分化正常2. Pituitary Amenorrhea 垂体

6、性闭经（20%）： hypophyseal tumor(垂体肿瘤):催乳激素细胞肿瘤,致闭经溢乳综合征hypophyseal infarct (垂体梗死)（Sheehan syndrome): 由于产后出血和休克导致垂体急性梗塞和坏死，使腺垂体丧失正常功能引起一系列腺垂体功能低下的症状，包括: 产后无乳、脱发、低促性腺激素闭经, 生殖器官萎缩，以及肾上腺皮质、甲状腺功能减退症状如低血压、畏寒、嗜睡等。empty sella syndrome(空蝶鞍综合征)：蝶鞍隔破坏，蛛网膜下腔向蝶鞍延伸，蝶鞍充满脑脊液3. Ovarian amenorrhea 卵巢性闭经（20%）XO syndrome o

7、r absence (先天性性腺发育不全或缺如)：Turners syndromepremature ovarian failure，POF(卵巢早衰)Ovaries histoclasia or resection (卵巢组织破坏或切除)Ovaries functional tumor (卵巢功能性肿瘤)Polycystic ovary syndrome, PCOS(多囊卵巢综合征)性腺先天性发育不全 占原发性闭经35性腺发育不全 、卵泡缺如、性征幼稚、雌激素水平低下， 属高促性腺激素闭经，75染色体异常，25染色体正常 染色体异常最常见Turners syndrome X染色单体45,XO

8、：性腺发育不全、第二性征发育不良；特殊体型：身材矮小（15.9nmol/l,提示有排卵),T; FSH40IU/L提示卵巢功能衰竭宫颈评分法阴道脱落细胞检查垂体功能测定垂体兴奋试验(GnRH刺激试验）：静脉注射GnRH刺激垂体，观察血FSH和LH变化垂体功能正常者刺激后30分钟比基值升高24倍反应低下或无反应垂体功能减退反应亢进PCOS激素：PRL25ug/L、FSH、LH头颅X片、CT其它检查 ： 染色体,甲状腺,肾上腺功能,腹腔镜,宫腔镜等闭经的诊断步骤 TreatmentsSystem treatments：diet regulation, psychotherapyMedicine：h

9、ormone supplemented or anti-excess 1）suppress PRL： Ergolactin 2）induce ovulation: CC、GnRH、GnRHa、HMG 3）HRT artificial cycle：用于II度闭经患者，目的维持性征，引起月经，防止骨质疏松 progestogen：适用于度闭经患者，目的保护子宫内膜 contraceptives：effective to PCOSOperation：structural disease 1）rectify malformation: atresia hymenalis (处女膜闭锁) 2）Asher

10、man syndrome ：adhesions isolation 3）tumor resection ：ovaries functional tumor, pituitary tumor ARTPolycystic Ovary Syndrome (PCOS)多囊卵巢综合症PCOS an outlineDefinition：以持续性无排卵、高雄激素或胰岛素抵抗为特征的内分泌紊乱的症候群。妇科内分泌临床常见疾患，占生育年龄妇女5-10%，我国的发病率尚缺少全国性、大样本、多中心研究。PCOS临床表现异质性，严重影响生殖功能，且雌激素依赖性肿瘤如子宫内膜癌发病率增加，相关的代谢失常包括高雄激素血症

11、、胰岛素抵抗、糖代谢异常、脂代谢异常、心血管疾病危险也增加。病因至今未明，诊断标准不统一，药物治疗方案混乱，对远期并发症缺乏合理防治措施。Origins of PCOS：1935 Stein-Leventhal描述闭经、多毛和双卵巢囊性增大的无排卵相关综合症（S-L征）。1990NIH制定PCOS诊断标准2003鹿特丹标准Obesity, fertility and PCOSGenetic aspects Intra-uterine Obesity AndrogensEnvironmental aspectsSingle gene PolygenicSteroid enzymesGonadot

12、rophinsCytokinesFat hormonesInsulin geneInsulin receptorInteractions of many factorsBirthweight Genetic Ovary genes Placental factors Dietary Placental Imprinting Leptin AromatisationEtiological factors of PCOSHot topics in aetiology of PCOSGenetic studiesRole of insulin in originsAndrogens and pren

13、atal exposurePrenatal growth and PCOSObesity, inflammation and environmentalDisorders of appetite and eatingPCOS perspective on phenotypeOligo- amenorrheaInfertilityObesityHirsutism （多毛）Acne（痤疮）Acanthosis nigricanes (黑棘皮症)Type 2 diabetesPrecocious puberty (性早熟)OtherEndocrinologistGynaecologistIntern

14、istDermatologistFertility expertfrom Fauser 2004Ultrasound of ovariesPCOS a problem of perspectiveTestosteroneLH:FSH ratioAnovulationInsulin resistancePCOS diagnostic criteria - 1990 NIH consensusChronic anovulationHyperandrogenism (clinical or biochemical)exclusion of other etiologiesDunaif. PCOS.

15、1992. Blackwell ScientificFauser 2004未将PCO作为诊断的主要症状Rotterdam consensus on PCOS 2003 ESHRE/ASRM meeting20 people with expertise on PCOSDiscussed diagnostic criteria for PCOSConsensus reached published 2004 oligoanovulation/anovulation hyperandrogenism (clinical and/or biochemical) polycystic ovaries

16、exclusion other aetiologies 2 out of 3 criteria wider criteria for family studiesFauser 2004Rotterdam consensus criteria for PCOSUltrasound consensus definitionsBalen et al Hum Reprod 9:505, 2003Technical issues: transvaginal, state of art equipment, well trained staff, D3-5 or following progestin b

17、leed, repeat scan if dominant follicle, calculate ovarian volume, count antral follicles, diameter 3 dimensions Either 12 or more follicles 2-9mm or ovarian volume over 10ml Subjective assessment follicle distribution should be ignored as well as stroma Only one ovary is adequate for diagnosis Does

18、not apply to OCP users: PCO does not mean PCOSWhat is the relationship between PCO and PCOS?Since 20-25% of women have PCO, we should not equate PCO with PCOS clinically as yet BUTPCO women get hyperstimulation like PCOS womenEvidence of similar degree of metabolic problems in women with PCO (no hyp

19、erandrogenaemia) (Norman et al 1995)Siblings of PCOS more hyperinsulinaemic (Norman et al 1995)Siblings of PCOS more insulin resistant, hyperandrogenaemic and more likely to get diabetes mellitus (Legro et al 2002, Yildiz et al 2003)More likely PCO is part of a spectrumWHO IIWHO II Anovulatory Infertility:Paradigm ShiftIrregular CyclesLHAndrogensInsulin& ObesityPCOPCOSL