Reproductive endocrinology of adolescent polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive-aged women, and it typically presents during adolescence. The objective of this review is to describe the clinical manifestations of PCOS in adolescent girls and the underlying basis for the altered reproductive physiology. Recognising adolescents at risk for PCOS and taking the appropriate steps to reduce circulating androgen levels is critical in reducing the clinical symptomatology of this disorder, and the development of adulthood infertility, diabetes, and metabolic syndrome in patients with PCOS.     

Adipose tissue,metabolic syndrome and polycystic ovary syndrome: from pathophysiology to treatment

In the last few years, polycystic ovary syndrome (PCOS) has deserved major attention because it is linked to the same cluster of events that promote the metabolic syndrome. This review will point out the relationships between fat excess, insulin resistance and the metabolic syndrome. Adipocytes are actually considered as endocrine cells that synthesize and release molecules (adipokines) that play an endocrine/paracrine role, such as adiponectin, atrial natriuretic peptide, leptin, resistin, tumour necrosis factor alpha (TNFα). Metabolic syndrome is a chronic low-grade inflammatory condition in which adipokines play a major role. Isolated adipocytes from women with PCOS express higher mRNA concentrations of some adipokines involved in cardiovascular risk and insulin resistance. However, environmental factors and lifestyle play a major role in determining the appearance of the phenotypes of PCOS. In morbid obese women with PCOS, bariatric surgery decreases bodyweight and fat excess and reverses hyperandrogenism and sterility. In lean or overweight women with PCOS, changes in lifestyle in combination with drugs reducing visceral fat and insulin resistance reverse the symptoms and signs of PCOS. Promising treatments for PCOS seem to be insulin sensitizers such as metformin and glitazones.     

Role of kisspeptin in polycystic ovary syndrome (PCOS)

Objective: Due to the complex relationship between kisspeptin and the hypothalamic-pituitary-gonadal axis, the study was planned to measure the kisspeptin levels in polycystic ovary syndrome (PCOS) and to analyze the correlations between kisspeptin and PCOS-related reproductive, metabolic changes.

Methods: The study was designed as a prospective study in Dokuz Eylul University between December 2011 and September 2013. A total of 285 PCOS cases and 162 controls were recruited. After the antropometric measeruments and physcial examination, blood samples were taken for biochemical analysis.

Results: PCOS group’s mean BMI was 24.32?±?3.40 and for the control group, BMI value was 23.44?kg/m²?±?4.08 (p?=?0.351). PCOS patients’ FSH level was 5.10?±?2.01 mIU/L, LH value was 7.75?±?4.31 mIU/mL, LH/FSH ratio was 1.70?±?1.28, DHEAS value was 221.84?±?105.02?mg/dl, total testosterone value was 50.51?±?27.93?ng/ml, free testosterone value was 2.52?±?1.05?pg/ml, SHBG was 63.74?±?45.62?nmol/L, LDL was 102.56?±?23.45?mg/dL, HDL value was 51.36?±?12.15?mg/dL, total cholesterol value was 214.85?±?39.27?mg/dL, triglyceride value was 112.95?±?46.88?mg/dL, Apo A1 value was 171.30?±?35.35?mg/dL, Apo B value was 71.08?±?19.07?mg/dL, Apo B/A1 ratio was 0.42?±?0.14, free androgen index was 13.77?±?14.15, fasting glucose value was 80.68?±?13.80?mg/dL, fasting insulin levels was 14.13?±?9.11 μiU/mL, HOMA-IR index was 2.76?±?2.34, AMH value was 5.93?±?3:33 in ng/ml, and found to be significantly higher (p?Conclusion: In this study, kisspeptin had a positive correlation with LH and leptin levels in PCOS. In fact, the serum levels of kisspeptin and leptin does not differ statistically between PCOS and healthy women. There are limited data in the literature with regard to changes in kisspeptin levels and its relation with metabolic and hormonal disturbances.     

Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS

OBJECTIVE: To determine the rate of clinically evident polycystic ovary syndrome (PCOS) among first-degree female relatives within families with a proband affected by PCOS. DESIGN: Clinical and biochemical evaluation of the mothers and sisters of 93 patients with PCOS. The diagnosis of PCOS was established by: [1] a history of oligomenorrhea, [2] clinical evidence (i.e., hirsutism) or biochemical evidence (i.e., elevated total or free T) of hyperandrogenism, and [3] the exclusion of related disorders. SETTING: Tertiary care university. PATIENT(S): Patients with PCOS and their mothers and sisters. INTERVENTION(S): Interview, physical examination, and hormonal testing on blood samples were performed for all subjects. MAIN OUTCOME MEASURE(S): The presence of hirsutism and hyperandrogenemia was determined in the mothers and sisters of the patients with PCOS. RESULT(S): Of the 78 mothers and 50 sisters evaluated clinically, 19 (24%) and 16 (32%) were affected with PCOS, respectively. A higher rate of PCOS was observed when only premenopausal women not taking hormones (i.e., untreated) were considered (i.e., 35% of mothers and 40% of sisters), consistent with amelioration of symptoms with hormonal therapy or aging. These rates of PCOS are significantly higher than that observed in our general population (approximately 4%) and suggest the involvement of a major genetic component in the disorder. CONCLUSION(S): The rates of PCOS in mothers and sisters of patients with PCOS were 24% and 32%, respectively, although the risk was higher when considering untreated premenopausal women only.     

High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS)

C-reactive protein (CRP) is a risk marker for type 2 diabetes mellitus and cardiovascular diseases. In polycystic ovary syndrome (PCOS), limited data are available on high-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of PCOS especially in Indian women. The objective was to determine serum hs-CRP concentration in adolescent women with and without PCOS and to assess possible correlations of serum hs-CRP levels with components of PCOS in Indian women. One hundred and sixty women with PCOS and sixty non-PCOS women having normal menstrual cycles were included. Clinical assessment included anthropometry, Ferriman–Gallwey (FG) score and blood pressure (BP) measurement. Laboratory evaluation included estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, hs-CRP, lipid profile, and insulin, and glucose after 2-h oral glucose tolerance test. Homeostasis Model Assessment Insulin resistance index (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) and glucose intolerance was calculated. FG score, LH, FSH, total Testosterone, HOMA-IR and QUICKI were significantly different among women with or without PCOS (p?p?>?0.05). A significant and positive correlation was found between hs-CRP and body mass index (BMI) (r?=?0.308, p?per se be associated with PCOS, rather can be related to fat mass in this subset of subjects.     

Androgens and insulin--two key players in polycystic ovary syndrome. Recent concepts in the pathophysiology and genetics of polycystic ovary syndrome

Androgens and insulin are endocrine key players in the pathophysiology of polycystic ovary syndrome (PCOS), a heterogenic condition of unexplained etiology and a suspected genetic background. Androgens mediate the clinical phenotype of the disease. Therefore,all criteria of the recent PCOS consensus definition are based on their biological effects. Insulin resistance, followed by compensatory hyperinsulinemia, is frequently found in patients with PCOS. Insulin resistance is correlated with a risk of metabolic complications of PCOS, and recent research has focused on possible long-term health consequences of the syndrome. Newest molecular genetic findings at the receptor level of both androgens and insulin support their pivotal role in PCOS. These results could help to better characterize the heterogenic disorder, enabling a refinement of existing individualized therapeutic strategies.     

The polycystic ovary syndrome

Much is known about the pathophysiology and pathogenesis of the polycystic ovary syndrome (PCO). The key clinical features are inappropriate gonadotropin secretion, altered production rates, binding and metabolism of steroids and androgen excess, all resulting in defeminization, anovulatory infertility, obesity and endometrial hyperplasia. Management should be based on the patient's reproductive goals. Adjunct measures can control hirsutism.     

多囊卵巢综合征患者的辅助生殖治疗结局

多囊卵巢综合征(PCOS)是育龄期妇女常见的内分泌紊乱性疾病,发病率达6%~10%。由于稀发排卵或无排卵,常常伴发不孕的问题。近年来,辅助生殖技术(ART)越来越多地应用于此类患者。研究表明不同类型的PCOS患者,如肥胖、高促黄体生成激素(LH)、高雄激素及胰岛素抵抗(IR),其ART助孕结局均较非PCOS患者差,虽然发生机制各有特点,但不同的病理生理异常相互作用,最终多反映为卵子质量下降,表现为PCOS患者ART治疗的临床妊娠率低、早期自然流产率高。本文就不同类型的PCOS患者的辅助生殖治疗结局以及影响其结局的因素进行论述,并探讨能够改善PCOS患者辅助生殖治疗结局的措施。     

Involvement of growth factors in the pathophysiology of polycystic ovary syndrome.

The etiology of polycystic ovary syndrome (PCOS) has not yet been fully elucidated but involves a disruption of normal ovarian function and multisystem sequelae. A combination of abnormally functioning genes whose expression is influenced by environmental, extra-ovarian factors determines the symptoms. Growth factors are heavily involved in the pathophysiology, either contributing to or as a consequence of the arrested development of follicles, abnormal steroidogenesis and hyperinsulinemia. Hyperactivity of a--transforming growth factor (TGFa) and epidermal growth factor (EGF) may block stimulation of aromatase and attenuate apoptosis of follicles and other factors may interface with the insulin-like growth factor (IGF) system preventing arrested follicles from becoming atretic and preventing the selection of a dominant follicle. IGF-binding protein concentrations are decreased by insulin, freeing biologically active IGF-I which augments the action of luteinizing hormone (LH) by inducing LH receptors, hyperactivating the enzymes P450c17a and 17,20 lyase resulting in hyperandrogenism. Growth hormone itself may be involved in the pathophysiology, as in normoinsulinemic PCOS patients it is hypersecreted and its actions on growth factors and their binding proteins are similar to those of insulin.     

Diet and nutrition in polycystic ovary syndrome (PCOS): pointers for nutritional management.

PCOS patients are not always markedly overweight but PCOS is strongly associated with abdominal obesity and insulin resistance. Effective approaches to nutrition and exercise improve endocrine features, reproductive function and cardiometabolic risk profile--even without marked weight loss. Recent studies allow us to make recommendations on macronutrient intake. Fat should be restricted to < or =30% of total calories with a low proportion of saturated fat. High intake of low GI carbohydrate contributes to dyslipidaemia and weight gain and also stimulates hunger and carbohydrate craving. Diet and exercise need to be tailored to the individual's needs and preferences. Calorie intake should be distributed between several meals per day with low intake from snacks and drinks. Use of drugs to either improve insulin sensitivity or to promote weight loss are justified as a short-term measure, and are most likely to be beneficial when used early in combination with diet and exercise.     

The role of plasma renin activity in distinguishing patients with polycystic ovary syndrome (PCOS) from oligomenorrheic patients without PCOS

All the components of the renin-angiotensin system have been identified in the human ovary. Renin plays a major role in folliculogenesis, and possibly in follicular atresia. Polycystic ovary syndrome (PCOS) is characterized by early follicular atresia. We studied whether assessment of plasma renin activity would be useful for diagnosing PCOS and distinguishing PCOS and non-PCOS in oligomenorrheic patients. Patients were divided into three groups: PCOS group (group 1, n = 40), non-PCOS oligomenorrheic group (group 2, n = 30) and ovulatory control group (group 3, n = 30). Plasma renin activity was determined in the early follicular phase of the menstrual cycle. Baseline serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, aldosterone and androgens (total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and 17α hydroxyprogesterone) were determined in all groups. The mean LH level was lower (4.94 ± 4.65 mIU/ml) in control patients than in PCOS patients (12.9 ± 1.75 mIU/ml) and non-PCOS oligomenorrheic patients (10.8 ± 1.65 mIU/ml). There was no statistically significant difference between the groups regarding FSH levels. The mean plasma renin activity was 3.47 ± 0.29 ng/ml in the PCOS group. The mean plasma renin activity was 1.59 ± 0.21 ng/ml the non-PCOS oligomenorrheic group (statistically significiant differrence). There was no statistically significant difference between the non-PCOS oligomenorrheic (1.59 ± 0.21 ng/ml) and control groups (1.2 ± 0.16 ng/ml). Use of plasma renin activity alone as a diagnostic marker in PCOS is not useful, because the clinical findings of PCOS are heterogeneous and the pathogenesis is unclear. However, it can be used together with other variables to diagnose women with PCOS and to distinguish non-PCOS oligomenorrheic women from those with PCOS.     

The metabolic syndrome in polycystic ovary syndrome

Approximately one-third to one-half of all women and adolescent girls with polycystic ovary syndrome (PCOS) has the metabolic syndrome, associated with increased risk for cardiovascular disease and type 2 diabetes. Evidence suggests that insulin resistance is the likely link between PCOS and the metabolic syndrome. Early screening for impaired glucose tolerance, even in adolescents, is recommended. Lifestyle modification with increased physical activity and weight reduction remains first-line therapy. Insulin-sensitizing drugs may also ameliorate features of the metabolic syndrome in PCOS but long-term prospective studies are needed to determine the role of these drugs in the prevention of the metabolic syndrome.     

The treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women in reproductive age. As for the treatment of this disease the lack of a clear etiology for PCOS has led to a symptom-orientated treatment. However, the overall aims of treatment are to induce ovulation for women desiring conception, to reduce androgen levels, to reduce body weight and to reduce long-term health risks of diabetes mellitus and cardiovascular disease. Clomiphene citrate (CC) is recommended as first line treatment for induction of ovulation in patients with PCOS by virtue of its efficacy, safety, and ease of administration. Alternatives for CC-resistant patients include gonadotrophin therapy (better with low-dose step-up protocol) and laparoscopic ovarian diathermy. Recently, recombinant FSH (rFSH) has been introduced in clinical practice and it seems more effective than urinary FSH as demonstrated by a significantly higher number of follicles recruited and embryos obtained with a shorter treatment period. The addition of GnRH-agonist to the stimulation protocol for women affected by PCOS could reduce premature luteinization and increase cycle fecundity. Other drugs under investigation are metformin and cabergoline. Hirsutism is the manifestation of hyperandrogenemia in PCOS. The primary goal of the treatment of hirsutim is central or peripheral androgen suppression using 3 groups of drugs: inhibitors of androgen production (oral contraceptives, GnRH analogues), peripheral androgen blockers (cyproterone acetate, flutamide, finasteride and spironolactone), and insulin-sensitizing agents (metformin). Weight reduction and exercise could also improve not only menstrual disturbances and infertility, but also insulin resistance and its adverse metabolic con-sequences.     

The genetics of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder. There is evidence for a genetic component in PCOS based on familial clustering of cases. The majority of the evidence supports an autosomal dominant form of inheritance. Steroidogenesis has been shown to be upregulated in PCOS theca cells, suggesting that the genetic abnormality in PCOS affects signal transduction pathways controlling the expression of a family of genes. Although a number of candidate genes have been proposed, the putative PCOS gene(s) has yet to be identified. Linkage and association studies implicate a region near the insulin receptor gene at chr 19p13.3. New genetic approaches, such as microarray technology, hold promise for elucidation of the pathophysiology underlying PCOS.