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PubMed2006

Endocrinological markers for assessing hyperandrogenemia in women classified as having polycystic ovary syndrome (PCOS) according to the revised 2003 diagnostic criteria.

The aim of this study was to investigate whether free testosterone estimated by calculation from total testosterone and sex hormone-binding globulin or free androgen indexes were more appropriate markers for assessing hyperandrogenemia in patients with polycystic ovary syndrome (PCOS). 107 Caucasian women were presented at our Division of Gynecological Endocrinology and Reproductive Medicine because of their infertility and hirsutism. Hirsutism was quantitatively assessed using a modified Ferriman-Gallwey score; oligo-ovulation or/and anovulation were assessed; polycystic ovaries were assessed; afterwards women were classified as having PCOS according to the revised 2003 consensus on diagnostic criteria for PCOS or classified as controls; endocrinological parameters were assessed using commercial immunoassays or were calculated. 50 women were classified as having PCOS; 57 women were classified as controls because they did not fulfill the criteria of PCOS. Calculated free and bioavailable testosterone, FAI, total testosterone, free testosterone assessed by immunoassay and DHEAS were significantly increased in women classified as having PCOS. All endocrinological markers for assessing hyperandrogenemia were elevated in the PCOS group regardless if they were assessed using commercial immunoassays or were calculated. Calculated values showed no diagnostic advantage in this study.

Adult↗

PubMed2004

Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women.

The new optical device, the lipometer, enables the noninvasive, quick, safe, and precise determination of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe a SAT topography (SAT-Top) like an individual "fingerprint" of a subject. This SAT-Top was examined in 16 women with polycystic ovary syndrome (PCOS) and compared to the body fat distribution of 87 age-matched healthy controls and 20 type-2 diabetic women. SAT-Top differences of these three groups were described and, to render the possibility of visual comparison, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. All PCOS patients had an android body fat distribution with significantly thinner SAT layers on the legs as compared to healthy controls. Moreover, a hierarchical cluster analysis resulted in two distinctly different groups of PCOS women, a lean (PCOSL) and an obese (PCOSO) cluster: compared to healthy women, lean PCOS patients had significantly lower total SAT development, even though height, weight, and body mass index did not deviate significantly. Especially on the legs, their SAT layers were significantly lowered, indicating a more "apple-like" fat distribution type. Obese PCOS women showed a SAT-Top pattern very similar to that of women with type-2 diabetes, although the mean age difference between these groups was more than 30 years. Compared to healthy controls, the SAT-Top of these obese PCOS patients was strongly shifted into the android direction, appearing as "super-apples" with a significantly increased upper trunk obesity to 237.8% and a significantly decreased leg SAT development to 79.8%.

Adipose Tissue↗

PubMed2004

Presence of metabolic risk factors in non-obese PCOS sisters: evidence of heritability of insulin resistance.

This study was performed to determine whether phenotypically healthy sisters of women with polycystic ovary syndrome (PCOS) have evidence of insulin resistance. We studied 54 women: 17 with PCOS, 17 sisters of these probands and 20 control women with similar age, body mass index (BMI) and waist-to-hip ratio (WHR). The PCOS sisters had neither clinical nor laboratory evidence of hyperandrogenism. However, estimated insulin resistance indices indicated decreased insulin sensitivity in PCOS sisters compared with the controls. No difference of insulin resistance indices was detected between the PCOS and their sisters. This finding provides additional evidence that there is a hereditary trait regarding insulin resistance in the PCOS families.

Adult↗

PubMed2000

Ultrasound criteria in the diagnosis of polycystic ovary syndrome (PCOS).

Not all women with the polycystic ovary syndrome (PCOS) on ultrasound (US) will have the syndrome, and clinical and biochemical features of PCOS may be present without US features. The sensitivity of US in detecting PCOS was, therefore, prospectively determined in 72 women (32 PCOS and 40 controls). The most sensitive features were the presence of 10 or more follicles (82% and 69% in the left and right ovary) and a peripheral distribution of follicles (81.8% and 71.9% in the left and right ovary). Although ovarian enlargement and stromal brightness were not as sensitive as the previous criteria, stromal brightness was most specific. Combining all the criteria predicted a diagnosis of PCOS or control correctly in 86.4% of cases. This study shows that established US criteria of polycystic ovaries remain of value in the diagnosis of PCOS; however, the discrepancy between the left and right ovaries is an interesting but unexplained finding.

Female↗

PubMed1997

Short-term GnRH-analogue administration in patients with PCOS and its impact on hemodynamics and hormonal profile.

PURPOSE: The ovarian response to 14 days of GnRH-analogue (GnRHa) application in patients with polycystic ovary syndrome (PCOS) was evaluated by measuring hemodynamic parameters and hormonal profile. METHODS: Twenty patients with PCOS represented the study group, and 22 patients with normal menstrual cycle (NMC) the reference group. The resistance index (RI) of uteroovarian arterial blood flow and serum level of LH and androstendione were measured on days 4, 13, and 22 of the cycle and after 14 days of GnRHa administration. RESULTS: On day 22 of the cycle the RI in the uterine artery was 0.86 in the PCOS and 0.82 in the NMC group. Throughout the cycle the ovarian arterial blood flow in both ovaries in the PCOS group was similar to that in inactive ovaries in the NMC group. After the 14-day GnRHa administration the RI of uteroovarian blood flow and the serum level of androstenedione remained unchanged in the PCOS group. CONCLUSIONS: RI in the uteroovarian blood flow and serum androstendione level in the PCOS group are not affected by 14-day GnRHa administration.

Androstenedione↗

PubMed2005

Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. METHODS: Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. RESULTS: Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). CONCLUSIONS: Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.

Adult↗

PubMed2007

Why does ovarian surgery in PCOS help? Insight into the endocrine implications of ovarian surgery for ovulation induction in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogeneity of clinical and endocrine features. Ovarian surgery for ovulation induction has been used in the management of clomiphene citrate-resistant anovulatory women with PCOS. Various types of ovarian surgery have been employed (wedge resection, electrocautery, laser vaporization, multiple ovarian biopsies and others) and all procedures result in an altered endocrine profile after surgery. The mechanism behind the reversal of endocrinological dysfunction in PCOS after ovarian surgery remains incompletely understood. This review scans the literature systematically to identify the endocrine changes after ovarian surgery in PCOS, in order to glean some knowledge of the mechanism involved. After ovarian surgery in PCOS, a rapid reduction in serum levels of all ovarian hormones is seen, in combination with increased serum levels of pituitary hormones. Folliculogenesis is then initiated and ovarian hormone production increases, synchronically with a reduction of pituitary hormones. Continuation of follicle growth in subsequent cycles after ovarian surgery occurs in an environment with less androgens and lower LH and FSH levels compared with pretreatment levels. The endocrine changes found after ovarian surgery in PCOS women seem to be governed by the ovaries themselves. Rapid reduced secretion of all ovarian hormones restores feedback to the hypothalamus and pituitary, resulting in appropriate gonadotrophin secretion. Initiation of follicular development seems to be induced by increasing FSH levels following a reduction of the follicle excess and (intra-ovarian) androgen levels. Additionally, anti-Müllerian hormone and gonadotrophin surge attenuating factor probably have a role in the endocrine changes.

Endocrine System↗

PubMed2001

The balance between MMP-9 and MMP-2 and their tissue inhibitor (TIMP)-1 in luteinized granulosa cells: comparison between women with PCOS and normal ovulatory women.

Polycystic ovarian syndrome (PCOS) involves follicular atresia, formation of multiple ovarian cysts and is frequently associated with a higher abortion rate. Follicular development, ovulation, formation of corpus luteum and its regression involve extensive tissue remodelling. Mammalian ovaries express a number of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP). We assessed the differences in production of MMP-2, MMP-9 and TIMP-1 by cultured luteinized granulosa cells from women with PCOS and normal ovulatory women after ovarian stimulation for IVF treatment. In follicular fluid from women with PCOS, levels of MMP-9 and MMP-2 were higher than the normal group, as was the basal production of these proteins by cultured cells. Basal production of TIMP-1 by cultured cells was not different between PCOS and normal groups. A time-dependent increase in the production of MMP-9 was observed in cells from both normal and PCOS women, although the increase was more pronounced in the latter. Thus the MMP-TIMP balance is shifted toward greater MMP activity in luteinized granulosa cells from women with PCOS.

Adult↗

PubMed2000

Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins.

Our aims were: 1. To investigate if women with PCOS who become pregnant using gonadotrophins have a higher incidence of gestational diabetes mellitus (GDM) compared to spontaneously pregnant matched control women, 2. To compare the prevalence of GDM in PCOS women with that in women with hypo/eugonadotrophic hypogonadism and in unexplained infertility and 3. To investigate differences in pregnancy outcomes between the groups. This was a retrospective case-control study. Women with PCOS were matched with a control by age, BMI, and ethnicity. There were 60 women with PCOS, 11 with hypogonadotrophic hypogonadism, 6 with eugonadotrophic hypogonadism, and 12 with unexplained infertility. Control women were those who attended a major public hospital for antenatal care and delivery We found no difference in the prevalence of GDM between the PCOS (22%) and the controls (17%) or between the PCOS and other groups. Women with GDM (diet or insulin controlled) had a significantly higher BMI than women without GDM (p = 0.019). There was no difference in pregnancy outcomes between the groups. There was a significant dependence of babies' birthweight on mother's BMI (p<0.001).

Adult↗

PubMed1998

Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS).

OBJECTIVE: To develop a self-administered questionnaire for measuring health-related quality of life (HRQL) in women with polycystic ovary syndrome (PCOS). METHODS: We identified a pool of 182 items potentially relevant to women with PCOS through semistructured interviews with PCOS patients, a survey of health professionals who worked closely with PCOS women, and a literature review. One hundred women with PCOS completed a questionnaire in which they told us whether the 182 items were relevant to them and, if so, how important the issue was in their daily lives. We included items endorsed by at least 50% of women in the analysis plus additional items considered crucial by clinicians and an important subgroup of patients in a factor analysis. We chose items for the final questionnaire taking into account both item impact (the frequency and importance of the items) and the results of the factor analysis. RESULTS: Over 50% of the women with PCOS labelled 47 items as important to them. Clinicians chose 5 additional items from the infertility domain, 4 of which were identified as important by women who were younger, less educated, married, and African-American. The Cattell's Scree plot from a factor analysis of these 51 items suggested 5 factors that made intuitive sense: emotions, body hair, weight, infertility, and menstrual problems. We chose the highest impact items from these 5 domains to construct a final questionnaire, the Polycystic Ovary Syndrome Questionnaire (PCOSQ), which includes a total of 26 items and takes 10-15 minutes to complete. CONCLUSIONS: We have used established principles to construct a questionnaire that promises to be useful in measuring health-related quality of life. The questionnaire should be tested prior to, or concurrent with, its use in randomized trials of new treatment approaches.

Adult↗

PubMed2004

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).

Since the 1990 NIH-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include: menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.

Clinical Trials as Topic↗

PubMed2006

Endothelial dysfunction in PCOS: role of obesity and adipose hormones.

PURPOSE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines. METHODS: A prospective study in 50 young women with PCOS (age: 25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and resistin were measured. RESULTS: PCOS, IMT was increased (P <.01), FMD was decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05), whereas leptin and resistin were not different compared with matched controls. Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and QUICKI correlated positively and negatively with IMT (P <.01). There was a significant negative correlation between adiponectin and IMT (P <.05). These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters. CONCLUSIONS: These data suggest that young women with PCOS have evidence for altered endothelial function. Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin. Both insulin resistance and adiponectin appear to be important parameters. It is hypothesized that the type of fat distribution may influence these factors.

Adipocytes↗

PubMed2006

Pregnancy complications in PCOS.

Complications of pregnancy associated with maternal PCOS include increased prevalence of early pregnancy loss (EPL), gestational diabetes (GDM), pregnancy-induced hypertensive disorders (PET/PIH), and the birth of small-for-gestational-age (SGA) babies. Increased risk of EPL has been attributed to obesity, hyperinsulinaemia, elevated luteinizing hormone concentrations, and endometrial dysfunction. Avoiding obesity before pregnancy and treatment with metformin are therapeutic options, also for the increased prevalence of GDM. Administration of metformin throughout pregnancy is a contentious issue. Screening pregnant women with PCOS for GDM and PET/PIH-especially if they are obese-is recommended, although data for a firm association between PCOS and PET/PIH is weak. Impaired insulin-mediated growth and fetal programming are possible explanations for a higher prevalence of SGA infants in mothers with PCOS. Only prospective studies employing a large cohort of women with well-defined PCOS compared with a control group matched for BMI and parity can solve the remaining questions.

Abortion, Spontaneous↗

PubMed2005

Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.

Reactive hypoglycemia (RH), which is a postprandial hypoglycemic state, occurs within 2-5 h after food intake. It is classified as idiopathic, alimentary, or diabetic reactive hypoglycemia. We studied the incidence of reactive hypoglycemia and looked for any correlations between it and the presence of insulin sensitivity and/or beta cell function in young lean polycystic ovary syndrome (PCOS) patients. This study was designed as a cross-sectional study in 64 lean young women with PCOS (BMI < or = 25 kg/m2). Various indices of insulin sensitivity and beta cell function derived from the oral glucose tolerance test (OGTT) results were used. We found the rate of RH to be 50% in lean young women with PCOS. DHEA-S and PRL levels were found to be lower in subjects with RH (P < 0.05 and P > 0.05, respectively). Beta cell function indices such as the insulinogenic index (at 120 min), CIR (at 120 min) and HOMA beta cell index were found to be insignificantly higher in the RH group than the nonreactive hypoglycemia (NRH) group. The 4 h glucose level, but not the 3 h glucose level, was significantly correlated with insulin resistance indices, such as fasting insulin level, HOMA-IR, Quicky index, and FIRI in the RH group. Significantly decreased DHEA-S levels were an interesting finding. In conclusion, there is an urgent need to investigate RH in lean young women with PCOS. Our results indicate that more definite insulin resistance occurs in subjects with RH in the fourth hour of the OGTT than those with RH in the third hour. In addition, RH in the fourth hour together with a low DHEA-S level may be predictive of future diabetes in young women with PCOS even when they are not obese.

Adult↗

PubMed2006

[Rotterdam consensus in adolescent girls: which investigations and how to interpret them to make the diagnosis of PCOS?].

The polycystic ovary syndrome (PCOS) is the most frequent cause of hyperandrogenism and anovulation in adult women as well as in adolescent girls. Since 2003 the diagnosis of PCOS has been based on the association of hyperandrogenism, oligoanovulation and polycystic ovary (PCO) morphology at ultrasound (at least 2 items out of 3). In adolescents however, PCOS features may be difficult to distinguish from the symptoms of the end of puberty. Moreover, transvaginal ultrasound examination is seldom possible, and it is difficult to get precise imaging of the ovaries by abdominal route. However, the diagnosis of PCOS in a hyperandrogenic and/or oligomenorrheic adolescent requires on the strict application of the Rotterdam criteria, as in adult women. Priority should be given to clinical features whereas pelvic ultrasound must be considered as optional. Few hormonal assays will serve mainly to make the differential diagnosis, in addition to clinical findings. Once established, the diagnosis of PCOS in an adolescent girl must lead to the detection of the metabolic syndrome by means of simple investigations. This will allow early prevention of its complications.

Adolescent↗

PubMed2002

Strategies to elucidate the mechanism of excessive theca cell androgen production in PCOS.

Polycystic ovary syndrome (PCOS) is characterized by increased ovarian androgen production. We have developed a strategy to identify differentially transcribed genes in PCOS theca cells. Using long-term cultures of normal and PCOS theca cells, we are characterizing the complete repertoire of differentially transcribed genes, the common transcription factor mediators, and the signal transduction cascade(s) that are abnormal in PCOS theca cells. The latter will be interrogated for mutations/genetic variants linked to PCOS.

Androgens↗

PubMed2001

Clinical management of PCOS.

The polycystic ovary syndrome (PCOS) is a heterogeneous condition with genetic predisposition. It is characterized by a myriad of symptoms including oligomenorrhea or amenorrhea, anovulation or infertility, hirsutism or acne. Insulin resistance appears to be an important factor in PCOS though the lack of an etiology has led to symptom oriented therapy which includes lifestyle modification, the use of cyclical progestagens and antiandrogens. Ovulation induction by drug therapy and ovarian drilling aims to treat subfertility in women with PCOS. Therapeutic approaches to PCOS remain an ongoing source of debate. Insulin sensitizing agents may bring new hope in therapy. Future research is aimed at shedding light on the pathophysiology so as to optimize treatment of women with PCOS.

Contraceptives, Oral↗

PubMed2026

Integrated multi-omics analyses identify an RAS-SLC11A2-associated molecular framework linking iron metabolism with PCOS-related cardiometabolic risk.

INTRODUCTION: PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside. METHODS: Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and in vitro functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM. RESULTS: SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation. CONCLUSION: This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.

Humans↗