多囊卵巢综合征病理生理的一些新认识

多囊卵巢综合征（PCOS）是以长期无排卵及高雄激素为特征的内分泌综合征,以不孕、多毛、无排卵、月经不调等为主要临床表现。PCOS超声下卵巢呈明显多囊性改变,并伴促性腺激素分泌异常。雄激素过多合成在PCOS发病中起关键性作用,膜细胞对颗粒细胞反应性增高、垂体分泌促黄体激素增多以及高胰岛素血症可能是卵巢雄激素合成过多的机制。胰岛素抵抗和肥胖的出现则可能使PCOS临床症状加剧。雄激素、胰岛素、促性腺激素和肥胖间的相互作用促成PCOS患者的生殖表型。     

多囊卵巢综合征

多囊卵巢综合征(PCOS)是妇科及生殖内分泌临床的一种常见疾病,可能是一些内分泌疾病的终点。常见主诉为多毛、肥胖、月经失调(主要是月经稀发)及不育,无排卵常见,经常需要用诱发排卵药物治疗其不育症。 PCOS患者雄激素水平升高,造成痤疮及多毛;卵巢内雄激素升高影响滤泡生成,参与了无排卵病理发生过程。虽然过量雄激素来源于卵巢,肾上腺也分泌一部分。垂体释放黄体生成激素(LH)增多,LH峰值有较大振幅。促性腺激素释放激素(GnRH)的释放过频导致LH出现脉冲,垂体敏感性增加,接受外源性GnRH时垂体促性腺激素(GTH)分泌增加,以致LH脉冲振幅增高。     

伴有雌激素生成的无排卵

慢性无排卵是以无周期的下丘脑-垂体-卵巢系统为特征的一组紊乱,其垂体促性腺激素分泌有3种方式:促性腺激素分泌过少;促性腺激素分泌正常;LH与FSH比例的不恰当增加。Yen将慢性无排卵综合征按病因分为4种:(1)下丘脑性-因LHRH不恰当地分泌所致;(2)垂体性一受体异常或α、β亚单位合成缺陷所引起的促性腺激素缺陷;(3)不恰当的反馈-使用性腺甾体激素(如口服避孕药),性腺外雌激素产生过剩,功能性雄激素过剩,产生雄激素或雌激素的肿瘤;(4)其它内分泌或代谢性功能紊乱-柯兴氏综合征、甲状腺素不足或过剩、催乳素或生长激素过多及营养不良。慢性无排卵综合征有多种临床、生化和形态学异常。临床表现从功能性子宫出血到月经过稀和闭     

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。     

多囊卵巢综合征

多囊卵巢综合征(PCOS)的内分泌学特点是中枢分泌过多的LH,及卵巢合成分泌过多的雄激素(A)及雌激素(E)的分泌异常.日本妇女所患的PCOS无A过多的男性化特征,使PCOS的临床问题更为复杂.本文目的是尽量明确PCOS的概念与定义,在病生理所见的基础上,提出诊断程序.对此症的治疗最近主要是用氯菧酚、糖皮质激素、促性腺激素等,而卵巢楔性切除     

17-β雌二醇对卵巢抗促性腺激素综合征患者血浆促性腺激素的影响

Savage综合征(卵巢抗促性腺激素综合征)是以闭经、促性腺激素分泌过多以及卵巢始基卵泡存在为特征的。卵巢抗促性腺激素综合征可能是由于:(1)垂体分泌无生物学活性的促性腺激素;(2)卵泡膜上促性腺激素受体的数目不足;(3)促性腺激素与卵泡膜上的促性腺激素受体的结合发生改变。据报告,患这种病症的妇女在卵巢长期衰     

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。     

高浓度雄激素诱导KNDy神经内分泌紊乱在多囊卵巢综合征发病机制中的研究进展

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是全世界女性最常见的生殖障碍性疾病之一,其症状主要表现为排卵、内分泌和代谢异常。尽管PCOS发病机制尚未明确,但是目前越来越多的研究证明高浓度雄激素诱导的神经内分泌紊乱在PCOS的发病中发挥作用,而下丘脑区域的KNDy神经元对女性的生殖功能有着重要的调控作用。近年研究发现,高浓度雄激素可能改变下丘脑区域KNDy神经元网络对促性腺激素释放激素的调节,从而干扰下丘脑-垂体-卵巢/肾上腺/脂肪细胞轴,使下游靶器官生成更多的雄激素即雄激素的恶性循环,加重PCOS的症状。因此,或许可通过在关键发育窗口期降低雄激素对神经内分泌的影响、恢复类固醇反馈的敏感性以及调整促性腺激素释放激素的分泌,进而使黄体生成素/卵泡刺激素（luteinizing hormone/follicle-stimulating hormone,LH/FSH）脉冲正常化来治疗PCOS。     

二甲双胍联合氯米芬-促性腺激素治疗多囊卵巢综合征

多囊卵巢综合征（PCOS）是排卵障碍性不孕的重要原因，与患者体内高雄激素、高胰岛素或胰岛素抵抗有关。其中部分患者经氯米芬治疗后能获得妊娠。但仍有相当数量的PCOS患者对氯米芬治疗无效。对此类患者使用氯米芬联合促性腺激素（CC—hMG／hCG）是目前治疗中常用的诱发排卵方法之一，但对PCOS患者使用促性腺激素治疗容易发生卵巢过度刺激综合征（OHSS），严重者可威胁患者生命。我们采用胰岛素增敏剂-二甲双胍联合氯米芬-促性腺激素治疗PCOS，取得肯定疗效，现报道如下。     

Cardiovascular risk factors are reduced with a low dose of acarbose in obese patients with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is defined by menstrual irregularity, hyperandrogenism, chronic anovulation, and enlarged ovaries with multiple follicles. Polycystic ovary syndrome is highly prevalent in women, affecting up to 10% of all women of reproductive age and reducing the possibility of spontaneous conception. In addition to altering reproductive function, PCOS has systemic implications, especially in the cardiovascular system. Cardiovascular risk (CVR) in PCOS patient increases because of insulin resistance, elevated androgen levels, and association with obesity. Those alterations promote cardiovascular risk factors, such as endothelial dysfunction, elevated homocysteine levels, left ventricular hypertrophy, and reduced high-density lipoprotein (HDL) cholesterol (1).     

Polycystic ovary syndrome: early detection in the adolescent

The primary clinical manifestations of polycystic ovary syndrome (PCOS) are hirsutism and irregular menstrual bleeding due to ovarian androgen excess and chronic anovulation. Historically, these features emerge late in puberty or shortly thereafter. The presence of insulin resistance or obesity, both commonly associated with this disorder, seems to further amplify the severity of the presentation. Perhaps, the most important finding is that of progressive hirsutism. Irregular menstrual bleeding is less reliable unless the duration of menstrual irregularity is persistent. However, mild hair growth and chronic anovulation are also regarded as normal components of the late stages of puberty and early adolescence and may persist for several years. It is for this reason that the diagnosis is often not made until later in life when endocrine and metabolic dysfunctions have been firmly established. The evolution of PCOS during early adolescence is not well-understood, but seems to involve abnormal activation of the hypothalamic-pituitary-ovarian-adrenal axis accompanied by specific morphologic changes of the ovary. Efforts to minimize the clinical features of PCOS in young adolescent girls depend on early diagnosis and timely suppression of excess ovarian androgen production.     

Hirsutism in a Gynaecological Context

Investigation of patients presenting with hirsutism to a gynaecological endocrine clinic revealed a high incidence of anovulation, obesity and elevated androgen levels. The underlying abnormality was polycystic ovarian syndrome (PCOS) in the majority of patients. Low levels of sex hormone binding globulin were common; these increased with oestrogen treatment. Treatment with a combined oral contraceptive pill and low dose spironolactone was often effective in reducing symptoms.     

The impact of obesity on reproduction in women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.     

Type 2 diabetes and polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) have multiple factors that contribute to increased diabetes risk, including: insulin resistance, beta-cell dysfunction, obesity, especially centripetal obesity, family history of type 2 diabetes, and personal history of gestational diabetes. Additionally there is some evidence to suggest that polycystic ovaries and chronic anovulation per se are risk factors. Identifying glucose intolerance and treating it are important aspects of the care for women with PCOS.     

A practical approach to the diagnosis of polycystic ovary syndrome

The diagnosis of polycystic ovary syndrome (PCOS) is primarily achieved through clinical history and physical findings. The principle features are hirsutism or biochemical evidence of excess androgen production and irregular menstrual bleeding caused by the chronic anovulation. Associated findings include insulin resistance with compensatory hyperinsulinemia and obesity. Ultrasound imaging of the ovary has facilitated the diagnosis. It is important to exclude conditions that may mimic PCOS, such as hyperthecosis, congenital adrenal hyperplasia, 21-hydroxylase deficiency, Cushing's syndrome, and androgen-producing neoplasms. These disorders are usually revealed by appropriate laboratory assessment. Screening tests include measurement of serum total testosterone, DHEA sulfate, and 17-hydroxyprogesterone. In addition, in the obese individual, determinations of glucose and insulin levels, as well as a lipid profile, are highly recommended.     

Association of metformin and pregnancy in the polycystic ovary syndrome. A report of three cases

BACKGROUND: Infertility is a common manifestation of the polycystic ovary syndrome (PCOS), a condition characterized by chronic anovulation, hyperinsulinemia and hyperandrogenism. Hyperinsulinemia leads to increased ovarian androgen production, resulting in follicular atresia and anovulation. Metformin, a medication that improves insulin sensitivity and decreases serum insulin levels, restores menstrual cyclicity and ovulatory function and may improve fertility rates in women with PCOS. We present three consecutive cases from our clinic that support this premise. CASES: Three patients were seen in the reproductive endocrinology clinic with documented PCOS, long-standing infertility and clinically diagnosed insulin resistance. The first patient had hyperandrogenic, insulin-resistant acanthosis nigricans syndrome and had been resistant to multiple courses of clomiphene citrate; the second exhibited hypertension, hyperlipidemia and glucose intolerance along with anovulation; and the third presented with poorly controlled type 2 diabetes and a desire to conceive. Each patient received metformin, which led to restoration of menstrual cyclicity and conception in all three cases. CONCLUSION: These three patients reflect the heterogeneous nature of PCOS, and treating their underlying insulin resistance with metformin resulted in pregnancy. These findings suggest that metformin may be a useful adjunct for treatment of infertility in patients with PCOS.     

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.

     

PCOS: diagnosis and management of related infertility

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is characterised by a combination of hyperandrogenism (either clinical or biochemical), chronic oligo/anovulation, and polycystic ovaries. It is frequently associated with insulin resistance and obesity. PCOS receives considerable attention because of its high prevalence and possible reproductive, metabolic, and cardiovascular consequences. It is the most common cause of anovulatory infertility. Ovulation induction with an aromatase inhibitor or anti-oestrogen is the first-line medical treatment. The aim of ovulation induction is monofollicular growth to avoid multiple pregnancy. The second-line treatments include gonadotrophins and laparoscopic ovarian drilling. The role and benefit of metformin in ovulation induction is uncertain. Woman with PCOS undergoing IVF are at significant risk of ovarian hyperstimulation syndrome. Women with PCOS are also at an increased risk of developing gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia.