胎儿期雄激素过多与多囊卵巢综合征

多囊卵巢综合征(PCOS)是引起育龄妇女不孕的主要原因。近年来动物实验揭示:出生前暴露于过多雄激素中,可导致雌性胎儿成年后产生PCOS样改变,包括高雄激素血症、LH/FSH比值升高、高胰岛素血症、卵巢多囊样改变和无排卵等。因此,有学者提出胎儿期雄激素过多可能是PCOS的致病因素之一,即胎儿时期受高雄激素的影响可导致成年后产生PCOS的症状与体征。     

多囊卵巢综合征高雄激素血症的治疗与研究进展

多囊卵巢综合征(PCOS)是一种高度异质性的临床内分泌疾病,以持续无排卵、高雄激素血症、卵巢多囊样改变为典型特征,常伴有胰岛素抵抗。体内过高水平的雄激素可导致卵泡的发育成熟过程受限,从而影响排卵。高雄激素血症形成原因复杂,其机制目前尚未完全阐明。本文主要从胰岛素、神经、体液调节与高雄激素血症形成的关系,肾上腺、脂肪等组织与高雄激素血症形成的关系,及基因多态性与高雄激素血症形成的关系等进行综述。同时介绍了目前针对PCOS高雄激素血症的治疗方法,包括西药治疗、中药治疗和中西医联合治疗等进展。     

多囊卵巢综合征高雄激素特征及管理

高雄激素是多囊卵巢综合征（PCOS）的主要临床特征之一，其可通过实验室检测雄激素水平及高雄激素的临床表现进行诊断。鉴于高雄激素影响卵泡发育，导致排卵障碍和月经紊乱以及引起多毛和痤疮等，而且与子宫内膜癌、糖尿病和心血管疾病的发生密切相关。因此，充分认识PCOS高雄激素特征并对其进行管理势在必行，此为PCOS综合治疗中的重要一环。     

多囊卵巢综合征的高雄激素血症及其治疗

据统计，65％～85％的高雄激素血症患者为多囊卵巢综合征（PCOS）患者。高雄激素血症在PCOS的发病过程中起到了重要作用。一方面，卵巢内高雄激素浓度抑制卵泡成熟，不能发育成优势卵泡，从而导致多个闭锁卵泡，使卵巢呈多囊性改变（PCO）；另一方面，由于雄激素增多造成的下丘脑-垂体-促性腺激素轴功能紊乱，以及增高的胰岛素的直接刺激，促使PCOS患者黄体生成激素（LH）增高，增高的LH又促进卵巢和肾上腺分泌雄激素，从而形成了一个雄激素过多，持续无排卵的恶性循环。[第一段]     

PCOS是卵巢对胰岛素超敏的综合征

多囊卵巢综合征(PCOS)以胰岛素抵抗或高胰岛素血症导致高雄激素血症为主要发病机制。卵巢内胰岛素调节雄激素合成的信号传导途径亢进,即卵巢局部组织对胰岛素作用的敏感性升高。胰岛素可以刺激正常妇女和PCOS妇女卵巢产生雄激素,但在体外PCOS妇女卵巢细胞对胰岛素刺激雄激素合成的反应性更高。多囊卵巢对促性腺激素的刺激敏感性也升高,即卵巢的反应性增强。部分发展为PCOS的妇女是由于卵巢内雄激素合成通路选择性的和特异性地对胰岛素敏感性增强引起的。因此,卵巢内部雄激素合成对胰岛素信号通路的过度敏感是一部分多囊卵巢妇女发展为PCOS的病因。     

双酚A对多囊卵巢综合征发病机制的影响

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是以高雄激素表型为典型特征的育龄期女性常见的内分泌疾病,其发病机制尚不明确,现多认为雄激素对其发病具有重要影响。双酚A(bisphenol A,BPA)作为环境内分泌干扰物,能够上调相关雄激素合成酶的表达,通过过量雄激素暴露来诱导PCOS的发生。研究表明BPA暴露能够抑制芳香化酶的活性,阻止雄激素与受体的结合,从而诱导高雄激素血症。BPA还可通过氧化应激、雌激素相关途径、下丘脑-垂体-卵巢轴以及对肥胖和胰岛素抵抗的调节等途径调控PCOS患者的卵巢功能。综述BPA通过调控高雄激素诱发PCOS的神经内分泌机制及相关信号通路,以期阐述BPA具体的生物学功能,为后续研究提供参考。     

多囊卵巢综合征远期并发症的预防策略

多囊卵巢综合征（PCOS）是育龄妇女最常见的内分泌疾病,肥胖、胰岛素抵抗、高胰岛素血症、高雄激素血症、血脂异常和月经异常作为PCOS的基本特征,互为因果、相互促进,可导致PCOS一系列远期并发症的发生。正确有效地干预上述因素可以明显改善患者的预后。     

多囊卵巢综合征患者高雄激素血症的诊治

多囊卵巢综合征（PCOS）高雄激素血症（高雄）临床特点是血清具生物学活性的雄激素水平超过正常值水平,并可具有痤疮、多毛、脂溢性皮炎、脱发等高雄的临床体征。病因主要是由于黄体生成激素（LH）分泌亢进及（或）胰岛素抵抗所致的高胰岛素血症。诊断可根据临床症状和血清学检测,须与其他引起高雄的内分泌疾病相鉴别。治疗应根据引起高雄的激素原因及治疗要求选择药物。     

多囊卵巢综合征胰岛素抵抗新进展

多囊卵巢综合征(PCOS)是一种常见的影响育龄期女性生殖和内分泌功能的特殊疾病,其临床表现异质性,以慢性无排卵、卵巢多囊样改变、高雄激素血症为主要临床表现.胰岛素抵抗是其发生、发展的重要病理生理机制之一,也是导致高雄激素血症和卵巢功能改变的重要原因.近年来,PCOS患者胰岛素抵抗的分子机制得到深入研究,为临床治疗提供了...     

多囊卵巢综合征胰岛素抵抗新进展

多囊卵巢综合征（PCOS）是一种常见的影响育龄期女性生殖和内分泌功能的特殊疾病,其临床表现异质性,以慢性无排卵、卵巢多囊样改变、高雄激素血症为主要临床表现。胰岛素抵抗是其发生、发展的重要病理生理机制之一,也是导致高雄激素血症和卵巢功能改变的重要原因。近年来,PCOS患者胰岛素抵抗的分子机制得到深入研究,为临床治疗提供了理论依据。综述PCOS胰岛素抵抗的分子机制研究和药物治疗进展。     

The role of the adrenal cortex in polycystic ovary syndrome

Adrenal androgen excess affects approximately 25% of PCOS patients. The exact etiology of this excess in PCOS patients is unclear. Some evidence that adrenal androgen excess may be a genetic trait. The adrenal androgen response to ACTH is highly individualized, and the relative response seems to be constant over time. In addition, there is a strong familial component to adrenal androgen levels in normal individuals and PCOS patients. It is possible that the tendency to overproduce adrenal androgens is an inherited risk factor for the development of PCOS. Overall, few hyperandrogenic patients actually have isolated deficiencies of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11-hydroxylase. The ovarian hormonal secretion in PCOS can affect adrenal androgen secretion and metabolism, although this factor accounts for only part of this abnormality. More likely, the adrenal androgen excess results from a generalized hyperresponsiveness of the adrenal cortex to ACTH, but without an increase in CRH or ACTH sensitivity. Although glucocorticoid administration may improve the ovulatory function of these patients, the results are modest and cannot be predicted by the circulating androgen levels.     

胚胎发育期高雄激素诱导多囊卵巢综合征患者内分泌紊乱的中枢机制

多囊卵巢综合征是一种育龄女性常见的内分泌紊乱疾病,以雄激素过多和胰岛素抵抗为主要特征,病理生理突出表现为卵泡发育不良.其发病原因至今尚不明确,现多认为雄激素在其发病中起重要作用.在胚胎早期发育过程中,过量雄激素暴露影响卵巢外神经内分泌系统,类固醇激素负反馈途径缺陷与促性腺激素释放激素神经元活性异常引起下丘脑-垂体-性腺...     

Umwelteinflüsse beim polyzystischen Ovarsyndrom

Background

With a prevalence of 6–20?%, polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathies among fertile women. It is characterized by hyperandrogenism and chronic anovulation and is highly associated with insulin resistance. Women with PCOS suffer from menstrual irregularity resulting probably in subfertility and from hirsutism, acne, and androgenetic alopecia. Furthermore, obesity is common in PCOS. Women with PCOS report a significant decrease in quality of life. Multiple factors are involved in the pathophysiology of PCOS. Besides a genetic background, environmental factors seem to influence development.

Aim

This article outlines the role of selected environmental factors in the pathophysiology of PCOS and describes the influence of intrauterine exposure to androgens, obesity, and endocrine disruptors like bisphenol A (BPA) on the PCOS phenotype.

Results and discussion

Intrauterine exposure to androgen excess due to hyperandrogenism of the mother may lead to the development of the PCOS phenotype including metabolic derangements. Obesity does not seem to cause PCOS, but is highly associated with a more severe phenotype of PCOS and aggravates metabolic risks associated with PCOS. BPA may enhance androgen synthesis and activity.

     

Irisin与多囊卵巢综合征代谢紊乱的研究进展

多囊卵巢综合征(PCOS)是育龄期妇女常见的生殖障碍及代谢功能紊乱性疾病,常伴有肥胖、胰岛素抵抗、雄激素过多和血脂异常等代谢异常,PCOS代谢紊乱比单纯的生殖障碍更复杂。鸢尾素(Irisin)为新近发现的在PCOS患者体内异常表达的肌肉因子,其主要作用机制为诱导白色脂肪组织的"褐变",增加产热和能量消耗,已有研究表明Irisin在肥胖、2型糖尿病、脂质代谢和心血管疾病、非酒精性脂肪肝等代谢障碍性疾病中发挥保护作用,但Irisin在PCOS的发生、发展中的作用尚不明确。本文综述Irisin在PCOS患者代谢紊乱发病机制中的作用,为PCOS的诊治提供新思路。     

Polycystic ovary syndrome,adipose tissue and metabolic syndrome

Purpose

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD).

Methods

A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulinresistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included.

Results

PCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle.

Conclusion

The high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.

     

Adrenocortical hyperresponsiveness to corticotropin in polycystic ovary syndrome patients with adrenal androgen excess

OBJECTIVE: To test the hypothesis that adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) is due to a generalized exaggeration in AA output in response to adrenocorticotropic hormone (ACTH), and that this abnormality is due to an identifiable alteration in the biosynthesis of AAs. DESIGN: Cross-sectional prospective controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Patients with PCOS (n = 9) and without (n = 9) AA excess and controls (n = 12) without hyperandrogenism, matched for age and body mass. INTERVENTION(S): Acute 60-minute ACTH test was performed on patients. MAIN OUTCOME MEASURE(S): Basal levels of dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, and basal (Steroid(0)) and the 60-minute ACTH-stimulated levels (Steroid(60)) of pregnenolone (PREG), progesterone (P4), 17-hydroxypregnenolone (17-HPREG), 17-hydroxyprogesterone (17-HP), dehydroepiandrosterone (DHEA), and androstenedione (A4) were measured. Adrenocortical activities of 17-hydroxylase (17-OH), 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase were estimated from product to precursor ratio, using Steroid(60) values. RESULT(S): Compared with PCOS patients without AA excess, PCOS patients with AA excess demonstrated significantly greater levels of DHEA(0) and A4(60). PCOS patients with AA excess had significantly higher activity of delta(5)17-OH, compared with PCOS patients without AA excess. CONCLUSION(S): Adrenal androgen excess in PCOS is associated with a greater delta(5)17-OH activity in response to ACTH.     

地塞米松对伴有肾上腺雄激素分泌过多的PCOS患者的疗效观察

目的:探讨地塞米松对伴肾上腺雄激素分泌过多PCOS患者的疗效。方法:采用前瞻、随机、对照的研究方法,将60例经达英-35治疗后高雄激素和临床表现仍然未能明显改善且伴有肾上腺雄激素分泌过多的PCOS不孕患者作为研究对象,将患者随机分成对照组(达英-35+安慰剂)和实验组(达英-35+地塞米松),所有患者治疗3个月,比较2组患者性激素水平、临床表现。随后给予氯米芬(CC)及人绝经期促性腺激素(hMG)促排卵治疗,比较分析临床结局。结果:所有患者治疗后雄烯二酮(A2)均降低,下降率组间无差异(P>0.05),实验组硫酸脱氢表雄酮(DHEAS)降低率、性结合球蛋白(SHBG)提高率明显好于对照组(P<0.05);实验组较对照组的痤疮及多毛症状改善明显(P<0.05),而体质量指数(BMI)及腰臀比(WHR)的改变不明显(P>0.05)。实验组比对照组的成熟卵泡率、排卵率及妊娠率效果更好(P<0.05)。结论:经用达英-35治疗后高雄激素血症和临床表现仍然未能明显改善,并伴肾上腺雄激素分泌过多的PCOS不孕患者,加用地塞米松,较单纯应用达英-35更能有效抑制高雄激素血症,提高SHBG,改善临床表现,提高成熟卵泡率、排卵率及妊娠率。     

济南市汉族育龄妇女PCOS患病状况的初步调查

目的:探讨济南市汉族育龄妇女多囊卵巢综合征(PCOS)患病状况及其临床特点。方法:以2003年ESHRE/ASRM建议诊断标准,按流行病学整群抽样方法调查济南市1027例育龄妇女中PCOS的患病状况。结果:(1)以ESHRE/ASRM 3条指标符合2条的原则检出PCOS 85例,群体患病率为6.46%;(2)检出的PCOS中稀发排卵、多囊样卵巢(PCO)、高睾酮(T)血症、临床高雄(F-G≥6多毛和痤疮)分别占89.4%、72.94%、57.65%、38.8%(1.18%和38.8%);每两项指标组合:稀发排卵+PCO、稀发排卵+高T、PCO+高T分别占60%、45.9%、38.8%;符合3条指标而临床、生化高雄仅有其一者占48.2%,两者均有占11.8%;不孕占7.06%、肥胖占8.23%。按汉族妇女F-G≥2分标准,群体PCOS中多毛率为37.65%。结论:(1)PCOS占济南市汉族育龄妇女的6.46%。(2)ESHRE/ASRM标准总体上是适合济南汉族育龄妇女PCOS检出的标准,多项指标可提高检出的特异度;(3)多毛作为临床高雄指标F-G≥2分更适于汉族人群。     

Neuroendocrine effects of androgens in adult polycystic ovary syndrome and female puberty

In addition to hyperandrogenism and ovulatory dysfunction, polycystic ovary syndrome (PCOS) is characterized by neuroendocrine abnormalities including a persistently rapid gonadotropin-releasing hormone (GnRH) pulse frequency. Rapid GnRH pulsatility favors pituitary secretion of luteinizing hormone (LH) over that of follicle-stimulating hormone (FSH). Excess LH stimulates ovarian androgen production, whereas relative deficits in FSH impair follicular development. The rapid GnRH pulse frequency is a result of reduced progesterone-mediated feedback inhibition of the GnRH pulse generator secondary to infrequent luteal phase increases in progesterone, as well as reduced hypothalamic sensitivity to progesterone feedback. Progesterone sensitivity is restored by treatment with the androgen receptor blocker flutamide. As such, hyperandrogenemia appears to play an important pathophysiologic role in PCOS. Adolescent hyperandrogenemia is believed to be a precursor to adult PCOS. In addition to increased LH concentrations and pulse frequency, some girls with elevated androgen levels also demonstrate reduced hypothalamic sensitivity to progesterone feedback. We hypothesize that excess peripubertal androgens may reduce the sensitivity of the GnRH pulse generator to sex steroid inhibition in susceptible individuals, resulting in increased GnRH pulse frequency and subsequent abnormalities in gonadotropin secretion, ovarian androgen production, and ovulatory function. Over time, these abnormalities may progress to the clinical hyperandrogenism and chronic oligo-ovulation typical of adult PCOS.     

青春期多囊卵巢综合征诊断与治疗中的过度与不足

现在的多囊卵巢综合征(PCOS)诊断标准都是针对成人而制定的,而青春期所表现出来的生理特点与PCOS的诊断标准有交叉,将针对成年人的PCOS诊断标准套用于青春期女性,势必造成过度诊断和过度治疗。建议对青春期女性暂不进行PCOS诊断,但不诊断并不意味着对她们不进行治疗,针对青春期出现的各种高雄、月经紊乱症状和代谢问题仍应积极进行相应的治疗。