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PubMed2001

Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population.

The aim of this study was to investigate the prevalence of diabetes mellitus, hypertension and cardiac complaints in a Dutch population with polycystic ovarian syndrome (PCOS) and to compare the results with the prevalence of these conditions in the Dutch female population, as retrieved from the Netherlands Health Interview Survey of Statistics Netherlands. A total of 346 PCOS patients were interviewed by telephone, with a mean age of 38.7 years (range 30.3--55.7) and a mean body mass index of 24.4 (range 17.5--55.8). Diabetes occurred in eight (2.3%), hypertension in 31 (9%) and cardiac complaints in three (0.9%) of the women. The prevalence of diabetes and hypertension differed significantly from the prevalence of these conditions in the Dutch female population (both P < 0.05). In PCOS women aged 45--54 years (n = 32) the prevalence of diabetes was four times higher (P < 0.05) and of hypertension 2.5 times higher (P < 0.01) than the prevalence of these conditions in the corresponding age group of the Dutch female population. Hypertension also occurred significantly (P < 0.05) more in the younger (35--44 years) PCOS group (n = 233), but this age group was significantly more obese (P < 0.01) when compared with figures of obesity of the Dutch female population. In conclusion, our data show that in a follow-up study of a relatively lean PCOS population, the prevalence of diabetes mellitus and hypertension was increased when compared with the Dutch female population, especially in women aged 45--54 years.

Adult↗

PubMed2003

Pregnancy outcome in women with PCOS and in controls matched by age and weight.

BACKGROUND: The aim of this study was to compare the pregnancy outcome, especially the prevalence of gestational diabetes mellitus (GDM), in a group of patients with polycystic ovary syndrome (PCOS), with a group of healthy weight-matched women. METHODS: Retrospectively, we evaluated the pregnancies of 66 women with PCOS, who had been treated for infertility and who delivered at our department. These were compared with a group of 66 age- and weight-matched controls. RESULTS: We did not find any significant differences in the prevalence of pregnancy complications such as gestational diabetes mellitus, pregnancy-induced hypertension (PIH) and premature deliveries between the group of PCOS patients and the controls. CONCLUSION: When differences in age and weight between PCOS patients and controls are negligible, PCOS is not associated with a higher risk of pregnancy complications.

Adult↗

PubMed2006

Low sex hormone-binding globulin is associated with low high-density lipoprotein cholesterol and metabolic syndrome in women with PCOS.

BACKGROUND: Decreased high-density lipoprotein cholesterol (HDL-C) and sex hormone-binding globulin (SHBG) levels, and the metabolic syndrome, are all closely associated with a higher prevalence of atherosclerotic cardiovascular disease. We investigated the association between HDL-C, SHBG and the metabolic syndrome in women with polycystic ovary syndrome (PCOS). METHODS AND RESULTS: Among 106 young Taiwanese women (mean age +/- SD, 24.9 +/- 4.8 years) with PCOS, 69 (65.1%) women had an HDL-C level <50 mg dl(-1). The level of HDL-C was highly correlated with that of serum SHBG (gamma = 0.6034, P < 0.0001). The SHBG level was significantly lower in subjects with an HDL-C <50 mg dl(-1) than that in subjects with an HDL-C > or =50 mg dl(-1). Using multiple linear regression models with adjustment for age, BMI and other anthropometric, metabolic, liver function and hormonal variables, we showed serum SHBG to be independently correlated with HDL-C. Based on logistic regression analysis with adjustment for age, the SHBG level was significantly lower in women with PCOS with the metabolic syndrome (odds ratio = 0.92, P = 0.003). CONCLUSIONS: Low levels of SHBG in women with PCOS were associated with low levels of HDL-C, independent of insulin resistance and obesity. The SHBG level was inversely related to the occurrence of metabolic syndrome, further strengthening the potential link between SHBG levels and cardiovascular disease in women with PCOS.

Adolescent↗

PubMed2006

Metformin treatment is effective in obese teenage girls with PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of menstrual disorders in teenage girls. Little information is available about the effects of metformin in adolescent girls with PCOS and its dose and its efficacy in regulating menstrual cyclicity and hyperandrogenic symptoms. We evaluated the effects of metformin treatment on ovulatory function, hirsutism, acne, hormonal patterns and body weight in adolescent girls with PCOS. METHODS: Eighteen girls, ranging in age from 15 to 18 years, were enrolled in the study. Clinical diagnosis of PCOS was based on the consensus criteria for PCOS accepted in May 2003 at Rotterdam. All subjects received 1700 mg/day metformin as tablets continuously for 6 months. They were then followed up for 6 months. RESULTS: Two patients complained of side effects for >2 weeks and interrupted treatment; they were not evaluated. All the others showed an improvement in menstrual cyclicity. Menstrual periods were ovulatory, with progesterone levels up to 6 ng/ml in luteal phase and a significant reduction in testosterone, androstenedione and free testosterone. BMI was restored within normal limits in all girls between 21 and 24 kg/m(2). Six months after the end of metformin treatment, menstrual cycles continued to be regular and ovulatory with normal BMI. Side effects were slight. CONCLUSIONS: The present results confirm the positive effects of metformin on menstrual periods and show that the drug can be administered to young women to improve ovulation and hyperandrogenic symptoms such as hirsutism, acne and weight gain.

Adolescent↗

PubMed2006

Is the PCOS diagnosis solved by ESHRE/ASRM 2003 consensus or could it include ultrasound examination of the ovarian stroma?

BACKGROUND: The clinical heterogeneity of polycystic ovary syndrome (PCOS) is mirrored by the unceasing debate on the most appropriate diagnostic criteria. METHODS AND RESULTS: To highlight differences and inconsistencies between NIH and ESHRE/ASRM criteria, we applied them to 375 patients with oligo/amenorrhoea and signs of hyperandrogenism. Among them, we identified 273 women with PCOS according to NIH, whereas up to 345 patients fulfilled ESHRE/ASRM criteria. The 72 patients, constituting the gap between the two classifications, exhibited a lower expression of clinical signs compared with the 273 patients matching both criteria. To the whole group, we then applied the ESHRE/ASRM criteria modified to include an easily reproducible ultrasound examination of the ovarian stroma (UCSC criteria). In this way, we identified 30 women who were healthy according to all criteria, 37 affected by PCOS according only to the ESHRE/ASRM Consensus, 35 affected according only to the UCSC and ESHRE/ASRM criteria and 273 who were considered to have PCOS by all criteria. These groups showed a progressively increasing expression of PCOS features. CONCLUSION: In the grey area between NIH and ESHRE/ASRM classifications, UCSC criteria could identify a subgroup of women, missed by NIH criteria, with more pronounced stigmas than those identified by ESHRE/ASRM criteria alone, and who may profit more from a targeted therapy.

Adolescent↗

PubMed2006

A novel SNP at exon 17 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS.

To investigate the association of single-nucleotide polymorphisms (SNPs) in exon 17 of the insulin receptor (INSR) gene with insulin resistance and INSR beta-subunit expression in polycystic ovary syndrome (PCOS) patients, a case-control study was carried out in an academic endocrinology clinic of China. One hundred and nine Chinese patients with PCOS and 107 healthy Chinese women as control were recruited. Their leukocytes and red blood cells were separated from blood samples, for SNP analysis with single-stranded conformation polymorphism and for the INSR beta-subunit expression detection by western blot analysis, respectively. A novel T/C SNP at codon Cys1008 (position 3128 of NM_000208) of INSR was found in two allele genotypes, i.e. the homozygous CC and the heterozygous TC. A higher frequency of the mutant homozygous CC was observed in the PCOS women with PCOS than that in the controls (21.1 versus 5.6%, P < 0.01). In contrast with the women with wild-type genotype, a significantly lower insulin sensitivity index in the women with each of the two mutant genotypes was revealed (CC: 0.335 +/- 0.026/TC: 0.346 +/- 0.027 versus TT: 0.367 +/- 0.029, P < 0.05). No relationship was found between the novel SNP and the INSR beta-subunit expression. We concluded that the novel T/C SNP at codon Cys1008 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS and that the association is not by the change of synthesis or secretion of INSR beta-subunit, but most possibly by the effects of this novel SNP on the function of INSR beta-subunit.

Adult↗

PubMed2025

Shared and divergent acute cardiovascular risk protein responses to lipid infusion in women with and without PCOS.

AIMS: Elevated circulating lipids are linked to cardiovascular disease (CVD), especially in insulin-resistant states like polycystic ovary syndrome (PCOS), but their effects on cardiovascular risk proteins (CVRPs) remain unclear. This study used a two-step approach to examine acute cardiovascular proteomic responses to lipid-induced metabolic stress. We first identified proteins altered by lipids and insulin in healthy control (HC) women, then assessed whether these responses were similar or divergent in women with PCOS. METHODS: In a randomised cross-over study, 10 healthy controls and 12 women with PCOS underwent 5-h saline (control) or intralipid infusions. After 3 h, a 2-h hyperinsulinemic-euglycemic clamp was initiated. Plasma CVRP expression was assessed at baseline, post-lipid (180 min) and post-clamp (300 min) using SOMAscan proteomics. STRING and pathway enrichment analyses were performed to explore functional associations. RESULTS: In the HC group, lipid infusion altered the expression of 11 out of 54 CVRPs including increases in RANK, IL2RA, TACI, SLAF5 and DCN (p <0.05) and decreases in THPO, BOC, SOD2, FGF23, and AgRP (p <0.05). Most changes reversed with insulin, but BOC, SOD2, MMP12, FGF23, and DCN remained dysregulated. In PCOS, responses mirrored the HC group except for lower AgRP following lipid infusion (p <0.01), and persistent elevation of SLAF5 and DCN following insulin (p <0.05). Enrichment analysis linked altered proteins to immune activation, cell proliferation, and cytokine-receptor signalling. CONCLUSION: Acute lipid infusion revealed shared and phenotype-specific proteomic responses linked to early vascular stress. In PCOS, persistent dysregulation suggests reduced metabolic adaptability, with exploratory signals that may complement established biomarkers of early cardiovascular risk.

Humans↗

PubMed2004

Clinical, biochemical and ultrasonographic characteristics of Scandinavian women with PCOS.

BACKGROUND: The aim was to investigate the clinical, biochemical and ultrasonographic characteristics of Scandinavian women with polycystic ovarian syndrome (PCOS), and to see whether there were any differences between eumenorrhoic and oligoamenorrhoic women. METHODS: Eighty women aged between 18 and 40 years with PCOS were investigated in a prospective study. The inclusion criteria were polycystic ovaries (PCO), body mass index (BMI) >25 kg/m(2) and at least one of the following: testosterone >2.5 nmol/L, sex hormone binding globulin (SHBG) <30 nmol/L, fasting C-peptide >1.0 nmol/L, oligoamenorrhea or hirsutism. RESULTS: Eumenorrhoic and oligoamenorrhoic women with PCOS did not differ in age, age at menarche, blood pressure, BMI, free testosterone index (FTI), insulin C-peptide or fasting glucose. A thicker endometrium and a smaller ovarian volume were found in eumenorrhoic compared to oligoamenorrhoic patients. There was linear association between BMI and the number of diagnostic criteria met. CONCLUSION: BMI was associated with the severity of the PCOS. There were no differences in basic clinical and biochemical parameters between eumenorrhoic and oligoamenorrhoic patients with PCOS.

Adult↗

PubMed2002

Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS.

We hypothesized that short-term calorie restriction would blunt luteinizing hormone (LH) hypersecretion in obese women with polycystic ovary syndrome (PCOS) and thereby ameliorate the anovulatory endocrine milieu. To test this hypothesis, 15 obese patients with PCOS and nine age- and body mass index-matched healthy women underwent 24-h blood sampling to quantitate plasma LH, leptin, and insulin levels. PCOS subjects were prescribed a very low caloric liquid diet (4.2 MJ/day) for 7 days and were then resampled. Basal and pulsatile LH secretion was threefold higher in PCOS subjects, but plasma insulin and leptin levels were not different in the calorie-replete state. Contrary to expectation, calorie restriction enhanced basal and pulsatile LH secretion even further. As expected, plasma glucose, insulin, and leptin concentrations decreased by 18, 75, and 50%, respectively. Serum total testosterone concentration fell by 23%, whereas serum estrone, estradiol, sex hormone-binding globulin (SHBG), and androstenedione concentrations remained unchanged. Enhanced LH secretion in the presence of normal metabolic and hormonal adaptations to calorie restriction points to anomalous feedback control of pituitary LH release in PCOS.

Adult↗

PubMed2006

The role of genes and environment in the etiology of PCOS.

Both genes and the environment contribute to PCOS. Obesity, exacerbated by poor dietary choices and physical inactivity, worsens PCOS in susceptible individuals. The role of other environmental modifiers such as infectious agents or toxins are speculative. Phenotype confusion has characterized genetic studies of PCOS. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, the follistatin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin receptor gene (but not involving this gene), as it has been identified in two separate studies, and perhaps most importantly has not yet been refuted by larger studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. To date, no gene has been identified that causes or contributes substantially to the development of a PCOS phenotype.

Cholesterol Side-Chain Cleavage Enzyme↗

PubMed2004

The molecular characteristics of polycystic ovary syndrome (PCOS) ovary defined by human ovary cDNA microarray.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders; it is characterized by polycystic ovaries, hyperandrogenism and chronic anovulation. To obtain a global view of those genes that might be involved in the development of this complex clinical disorder, we used recently developed cDNA microarray technology to compare differential gene expressions between normal human ovary and ovaries from PCOS patients. A total of 9216 clones randomly selected from a commercial human ovary cDNA library were screened. Among them, 290 clones showed differential expressions, including 119 known genes and 100 known or unknown expressed sequence tags (ESTs). Among 119 known genes, 88 were upregulated and 31 downregulated in the PCOS ovary, as compared with normal human ovary. These differentially expressed genes are involved in various biologic functions, such as cell division/apoptosis, regulation of gene expression and metabolism, reflecting the complexity of clinical manifestations of PCOS. The molecular characteristics established from our study will further our understanding of the pathogenesis of PCOS and help us to identify new targets for further studies and for the development of new therapeutic interventions.

Base Sequence↗

PubMed1994

Ovarian electrocautery in the treatment of women with polycystic ovary syndrome (PCOS). Factors affecting the results.

During the years 1979-91 252 women with polycystic ovarian syndrome (PCOS) have been treated with ovarian electrocautery through the laparoscope in Aker University Hospital. Ovulation was obtained in 92% of the total series, and pregnancy in 84% of the women with PCOS as the sole cause of their infertility. Additional treatment with clomiphene citrate to the non-responders increased the pregnancy rate to 89%. The response to ovarian electrocautery was influenced by body weight, with an ovulation rae of 96-97% in the slim and moderately obese women decreasing to 70% in the really obese ones. When ovulation was established, the pregnancy rate per se was independent of body weight-when ovulation was established, the pregnancy rates of slim and overweight women with PCOS being 92% and 95%, respectively. In the responders (who ovulated following ovarian electrocautery), the annual rate of cessation of ovulation was 3-4% only. Even after a period of contraceptive use following the ovarian electrocautery, ovulation was resumed and pregnancy obtained within a few months. Therefore, ovarian electrocautery is proposed as the primary treatment in women with PCOS undergoing laparoscopy for any reason, infertility being a present, future or hypothetical problem only. When, on the other hand, infertility is not an issue, PCOS per se constitutes no reason to perform laparoscopy.

Body Weight↗

PubMed1999

Growth hormone response to oral glucose tolerance and insulin tolerance tests in patients with PCOS.

Polycystic ovary syndrome (PCOS) is characterized by its heterogeneity. This is the reason for the diversity in the clinical manifestations and laboratory findings. In this study we examined the serum levels of growth hormone (GH) in 15 women with PCOS and 5 healthy volunteers following oral administration of 75 gr glucose (OGTT) and intravenous administration of insulin (ITT). The OGTT produced no significant difference between the two groups of women, in the ITT there was a difference between the GH response of the women with PCOS and that of the healthy women. The group with PCOS showed a later, more prolonged, higher response, indicating that the hypothalamus is probably involved in PCOS.

Adult↗

PubMed2003

Polycystic ovary syndrome (PCOS), insulin resistance and insulin-like growth factors (IGfs)/IGF-binding proteins (IGFBPs).

Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of ovarian function. Hyperinsulinemia with insulin resistance is believed to be a key link in the enigmatic generation of the symptoms of PCOS such as anovulatory infertility and hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinemia. A growing body of evidence suggests that PCOS patients with hyperinsulinemia have a higher risk to develop diabetes mellitus, hypertension and cardiovascular disease as compared to age-matched women. Although oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies, weight loss should also be vigorously encouraged to ameliorate the metabolic consequences of PCOS. In addition, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies to alleviate hyperinsulinemia in PCOS. Finally and most importantly, early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.

Androgen Antagonists↗

PubMed2003

Endocrine characteristics of polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is probably the most prevalent endocrinopathy in women and the most common cause of anovulatory infertility. Patients with PCOS have clinical and biochemical features consistent with the ultrasound diagnosis and they are likely to face the problems of hyperandrogenism, subfertility and recurrent miscarriage. The aim of the present review is to summarize our present knowledge on the hormonal background of this very prevalent syndrome and to give some clinical examples how the present knowledge can be applied to treat PCOS patients according to their current problem, such as menstrual cycle disorder, hirsutism, infertility or to prevent late consequences as diabetes mellitus. The etiology and pathogenesis of PCOS is still a matter of controversies, but it is apparent that inappropriate gonadotropin secretion, obesity, hyperinsulinism and insulin resistance are the major determining factors in the development of ovarian hyperandrogenism an chronic anovulation. Reversal of insulin resistance in PCOS constitutes the fundamental goal in the management of hyperandrogenic anovulatory infertility and in the prevention of long-term consequences. The value of the insulin sensitizer metformin therapy awaits further evaluation and it should be integrated in the spectrum of therapeutical options that include the discussed surgical methods and GnRH analogues as well.

Contraceptives, Oral, Hormonal↗

PubMed1997

[Polycystic ovary syndrome: PCOS].

Polycystic Ovary Syndrome(PCOS) was originally reported by Stein and Leventhal in 1935, as an syndrome with bilateral polycystic ovaries, menstrual abnormality, hirsutism and obesity etc. After this report the diagnosis of "Polycystic Ovary" was abused for the patient only with polycystic change of ovaries, so that, the concept or definition of PCOS has became unclear and controversial. In this review, a classification of PCOS according to the presence of hyperandrogenemia and/or hirsutism will be shown to reconstruct the concept or definition of PCOS. And usefulness of this classification will be revealed by showing endocrinological and morphological aspect of each class. Furthermore, new therapeutic approaches for PCOS with pure FSH injection in combination with GnRH analog against the onset of OHSS, or drillings of antral follicles with CO2 or KTP laser will be also shown in this review.

Female↗

PubMed2005

Metformin treatment of PCOS during adolescence and the reproductive period.

Insulin resistance is a common feature of PCOS. Hyperinsulinemia has been causally linked with all features of the syndrome, such as hyperandrogenism, reproductive disorders, and metabolic disturbances. Several insulin-sensitizing agents have been tested in the management of PCOS. Metformin is the only drug currently in widespread clinical use for PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of the menstrual cycle, less pronounced hyperandrogenism and cardiovascular risk factors, and some improvement in the response to therapies aimed at induction of ovulation. In adolescent girls who are anovulatory and moderately obese, metformin administration can have a normalizing effect on multiple aberrations within the endocrine-metabolic status. During the reproductive period, metformin administration can improve reproductive function and the establishment of pregnancy. A role of metformin in prevention of gestational diabetes and hypertensive complications of pregnancy has yet to be shown. Finally, any real benefit of insulin-lowering treatment in terms of lesser cardiovascular risk in women with PCOS women remains to be demonstrated.

Adolescent↗

PubMed2005

Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic?

OBJECTIVE: The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups. METHOD: In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI < 25) (n = 37); Group 2: normoinsulinemic, overweight (BMI: 25-29.9) (n = 19); Group 3: normoinsulinemic, obese (BMI > or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio < 4.5 mg/10(-4) U), lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments. RESULT(S): We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P < 0.05). The duration of the menstrual cycle significantly decreased in the normoinsulinemic obese sub-group on metformin therapy (P < 0.05). Metformin had a significant effect on hirsutism scores in hyperinsulinemic lean women (P < 0.05) and decreased DHEAS levels significantly in the lean hyperinsulinemic and normoinsulinemic groups (P < 0.05). Metformin had significant effects on ovulation in only lean hyperinsulinemic women (P < 0.05). CONCLUSIONS: Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.

Adiposity↗