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PubMed2006

Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: A preliminary report.

BACKGROUND: In the Systematic Treatment Enhancement Program for Bipolar Disorder, we showed that valproate is associated with new-onset menstrual-cycle irregularities and hyperandrogenism in 10.5% of 86 women. We now determine whether polycystic ovarian syndrome (PCOS) features reverse on valproate discontinutation. METHODS: Women with valproate-associated PCOS and those at risk for PCOS (valproate use < or =6 months) were re-evaluated for PCOS. RESULTS: Follow-up (mean 17 months) assessments were completed in 14 women (5 with treatment-emergent PCOS, 9 on valproate < or =6-month). Of seven women who developed valproate-associated PCOS, PCOS reproductive features remitted in three of four discontinuing valproate and persisted in all 3 continuing valproate. Menstrual-cycle irregularities improved among valproate-discontinuers whose PCOS features remitted (p = 0.01). There was a trend toward lower serum testosterone (p = 0.06). Body-weight and polycystic ovarian morphology did not change. CONCLUSIONS: In the first longitudinal bipolar-disorder study of valproate-associated PCOS, most valproate-discontinuers had improved reproductive features of PCOS despite static body-weight.

Adolescent↗

PubMed2005

Outcome of intracytoplasmic sperm injection in patients with polycystic ovary syndrome or isolated polycystic ovaries.

OBJECTIVE: To determine the intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) performance of patients with polycystic ovary syndrome (PCOS) and isolated polycystic ovarian (PCO) morphology. DESIGN: Case-control study. SETTING: IVF Center, Hacettepe University Faculty of Medicine. PATIENT(S): Ninety-nine consecutive infertile women (n = 109 cycles) with PCOS and 58 patients (n = 58 cycles) with isolated PCO morphology were recruited. The control group consisted of 210 patients (n = 232 cycles) with isolated male factor infertility necessitating ICSI. All three groups were matched for female age and body mass index. INTERVENTION(S): Controlled ovarian hyperstimulation and ICSI. MAIN OUTCOME MEASURE(S): Oocyte number, fertilization rate, embryo quality, clinical pregnancy rate, implantation rate, and ovarian hyperstimulation syndrome (OHSS). RESULT(S): Six (5.5%) cycles in the PCOS group, 6 (10.3%) cycles in the PCO-only group, and 10 cycles (4.3%) in the control group were canceled. Despite a significantly lower total FSH dose used, a significantly higher serum E2 level was attained in both the PCOS and the PCO-only groups compared to the control group. The PCOS and PCO-only groups had significantly higher numbers of retrieved oocyte-cumulus complexes and metaphase II oocytes compared to the control group. The fertilization rates did not differ among the three groups. The mean number of embryos transferred was comparable among the three groups; however, the mean number of grade 1 embryos was significantly higher in the PCOS and PCO-only groups compared to the controls. The clinical pregnancy rates per ET of both the PCOS (66%) and the PCO-only (60%) groups were significantly higher than that of the control group (44%). However, the implantation rates were comparable among the three groups. Four cycles (3.7%) in the PCOS group had OHSS necessitating hospitalization. The respective figures in the PCO-only and the control groups were 1 (1.7%) and 3 (1.3%). CONCLUSION(S): Patients with the full-blown picture of PCOS or isolated PCO-only morphology behave exactly in the same manner during all stages of assisted reproduction. Owing to the availability of more fertilized oocytes and grade 1 embryos, patients with PCOS or PCO-only morphology are associated with higher clinical pregnancy rates per ET compared to patients with isolated male factor infertility.

Adult↗

PubMed2006

Polymorphism in HSD17B6 is associated with key features of polycystic ovary syndrome.

OBJECTIVE: To investigate polymorphisms in androgen metabolism regulators that are implicated in the etiology of polycystic ovary syndrome (PCOS) in vitro; to investigate HSD17B6 and GATA6 to determine whether these genes are associated with susceptibility to PCOS or key phenotypic features of patients with PCOS. DESIGN: Case-control association study. SETTING: Participants with PCOS were recruited from a clinical-practice database, and controls, from the general community. PATIENT(S): One hundred seventy-three patients with PCOS and who were of Caucasian descent and conformed to the National Institutes of Health (NIH) diagnostic criteria; 107 normally ovulating women of Caucasian descent from the general community. INTERVENTION(S): Drawing of blood for DNA extraction. MAIN OUTCOME MEASURE(S): Frequency of HSD17B6 and GATA6 polymorphisms in cases and controls. Association of single-nucleotide polymorphisms from HSD17B6 in subjects with PCOS with key phenotypes of PCOS: androgen status, insulin resistance, and body mass index. RESULT(S): Allele distribution for the single-nucleotide polymorphism rs898611 in HSD17B6 was significantly different between PCOS and control subjects (P=.03). Presence of the polymorphic allele was associated with reduced fasting glucose-insulin ratio (P=.02) and increased homeostasis model assessment (P<.01) and body mass index (P<.001) as well as with reduced T (P=.03) in the PCOS group. No association was seen between GATA6 and any of the variables studied. CONCLUSION(S): These data suggest that polymorphisms in the HSD17B6 gene are associated with PCOS and key clinical phenotypes of the disorder.

Adult↗

PubMed2004

Insulin secretion in women who have polycystic ovary syndrome and carry the Gly972Arg variant of insulin receptor substrate-1 in response to a high-glycemic or low-glycemic carbohydrate load.

OBJECTIVE: We evaluated metabolic parameters in Chilean women with polycystic ovary syndrome (PCOS) who were carriers and non-carriers of the glycine-to-arginine substitution at codon 972 (Gly972Arg) variant of insulin receptor substrate-1 and to assess insulin response after oral high- and low-glycemic loads METHODS: In 146 women with PCOS and 97 healthy women (HW), Gly972Arg genotypes were obtained by polymerase chain reaction, and an oral glucose tolerance test was performed with glucose and insulin measurements. An insulinogenic index, a homeostasis model assessment for insulin resistance, and whole-body insulin sensitivity index (composite) were calculated. Eight carriers and eight non-carriers (four PCOS and four HW, respectively) underwent a 50-g glucose (high glycemic) or 50-g fructose (low glycemic) load with serum glucose and insulin measurements at 15-min intervals for 3 h. RESULTS: The frequency of the Gly972Arg variant was higher in PCOS patients than in HW (P < 0.05). The insulinogenic index was lower in HW carriers than in non-carriers (P < 0.05). In PCOS carriers, 2-h insulin was higher than in those without the mutation. In overweight PCOS carriers, the homeostasis model assessment for insulin resistance was higher and the insulin sensitivity index was lower than in PCOS patients without the mutation. In HW carriers, a delay in the maximal response of insulin secretion was observed, with a decrease of 26.7% in insulin concentrations 30 to 60 min after the 50-g glucose load. Glucose concentrations increased by 19.7% between 60 and 120 min. Glucose concentrations between 0 and 120 min were 14.9% higher in PCOS carriers than in non-carriers after the 50-g glucose load. CONCLUSIONS: In HW, this polymorphism appears to be associated with a decrease in insulin secretion; in PCOS women, this polymorphism interacts with obesity to influence insulin resistance, thus contributing to the pathogenesis of the metabolic component of PCOS.

Adolescent↗

PubMed2000

Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome.

OBJECTIVE: To determine whether testosterone levels change as women with the polycystic ovary syndrome (PCOS) grow older. DESIGN: A follow-up cross-sectional study of a cohort of women with PCOS identified up to 20-25 years ago. SETTING: Women with PCOS were recruited primarily from practice records between 1970 and 1990. Voter registration tapes and household directories were used to identify age-, race-, and neighborhood-matched controls. PARTICIPANT(S): Eighty-four women with PCOS, 20-57 years of age, and 37 age-matched controls participating in a study of the risk for cardiovascular disease in women with PCOS. INTERVENTION(S): Clinical data were collected by questionnaire and fasting blood samples were obtained randomly throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Total and non-SHBG-bound testosterone levels. RESULT(S): Total and non-SHBG-bound testosterone levels were similar in women with PCOS who were 20-42 years of age but were reduced by approximately 50% among women 42-47 years of age and remained stable in women older than 47 years of age. Testosterone levels were increased in younger and older women with PCOS compared with controls but were similar to controls in women 42-47 years of age. CONCLUSION(S): Hyperandrogenism partly resolves before menopause in women with PCOS. This change may explain the tendency of women with PCOS to cycle regularly as they grow older. Testosterone levels remain elevated in older women with PCOS, however, and may contribute to their increased risk for cardiovascular disease, endometrial cancer, and other diseases.

Adult↗

PubMed1997

Responses of polycystic ovarian syndrome and related variants to low-dose follicle stimulating hormone.

OBJECTIVE: To determine whether patients with classical polycystic ovarian syndrome (PCOS) respond differently to low-dose FSH therapy in comparison with anovulatory patients (PCOS-like) where only some features of PCOS are present. METHODS: Two groups of patients were studied. The PCOS group (25 patients, 51 cycles) and the PCOS-like group (38 patients, 57 cycles) were treated with the same protocol of purified FSH, commencing with an initial dosage of 75 IU/day and increasing by 37.5 IU/day after 14 days, where necessary. Estradiol levels and ultrasonographic evidence of follicular development were used for monitoring. RESULTS: PCOS patients required more ampules of FSH, needed more days of gonadotropin stimulation, secreted higher levels of E2 and had increased numbers of intermediate follicles compared to the PCOS-like group. CONCLUSIONS: This study demonstrated significant differences between PCOS and other PCOS-like conditions when treated with low-dose FSH. Classification of the subvariants of PCOS may have therapeutic implications.

Adult↗

PubMed1999

Pseudo-cyclic oligonucleotides: in vitro and in vivo properties.

We have designed and studied antisense oligodeoxynucleotides (oligonucleotides; oligos) which we call 'pseudo-cyclic oligonucleotides' (PCOs). PCOs contain two oligonucleotide segments attached through their 3'-3'- or 5'-5'-ends. One of the segments of the PCO is an antisense oligo complementary to a target mRNA, and the other is a short protective oligo that is 5-8 nucleotides long and complementary to the 3'- or 5'-end of the antisense oligo. As a result of complementarity between the antisense and protective oligo segments, PCOs form intramolecular pseudo-cyclic structures in the absence of the target RNA. The antisense oligo segment of PCOs used for the studies described here is complementary to an 18-nucleotide-long site on the mRNA of the protein kinase A regulatory subunit RIalpha (PKA-RIalpha). Thermal melting studies of PCOs in the absence and presence of the complementary RNA suggest that the pseudo-cyclic structures formed in the absence of the target RNA dissociate, bind to the target RNA, and form heteroduplexes. The results of RNase H cleavage assays suggest that PCOs bind to complementary RNA and activate RNase H in a manner similar to that of an 18-mer conventional antisense PS-oligo. In snake venom (a 3'-exonuclease) or spleen (a 5'-exonuclease) phosphodiesterase digestion studies, PCOs are more stable than conventional antisense oligos because of the presence of 3'-3'- or 5'-5'-linkages and the formation of intramolecular pseudo-cyclic structures. PCOs with a phosphorothioate antisense oligo segment inhibited cell growth of MDA-MB-468 and GEO cancer cell lines similar to that of the conventional antisense PS-oligo, suggesting efficient cellular uptake and target binding. The nuclease stability studies in mice suggest that PCOs have higher in vivo stability than antisense PS-oligos. The studies in mice showed similar pharmacokinetic and tissue distribution profiles for PCOs to those of antisense PS-oligos in general, but rapid elimination from selected tissues.

Animals↗

PubMed2004

Leptin and its association with polycystic ovary syndrome: a twin study.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy with symptoms such as obesity, insulin resistance and hyperandrogenemia. PCOS might be the result of a genetic disorder. Genetic discrepancy in the production of leptin, a product of the obesity gene, may lead to various endocrinopathies such as PCOS. The objective of this study was first, to ascertain the incidence of PCOS, using the gold standard; second, to ascertain the genetic property of leptin; and third, to evaluate the association between leptin concentration and PCOS. A total of 154 Tehran-resident female-female twins were studied. They included 48 pairs of monozygotic (MZ) and 29 pairs of dyzygotic (DZ) twins, aged 15-45 years. Clinical, ultrasound and biochemical findings were used to diagnose PCOS. The incidence of PCOS using biochemical and clinical features was 16.2%. The correlation coefficient between serum leptin levels of MZ twins was higher than that of the DZ twins. The serum level of leptin was similar between subjects with or without PCOS, irrespective of their zygosity. It was concluded that the incidence of PCOS is high among twins, and that leptin is likely to be genetically determined, although the effect of environmental factors cannot be denied. This study did not find any association between the diagnosis of PCOS and leptin level. However, the link between the two may lie with other entities such as eating disorders and/or obesity.

Adolescent↗

PubMed2006

Adiponectin is an independent determinant of insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is frequently associated with insulin resistance and a consequent increased risk of metabolic diseases. The aim of the present study was to investigate the role of adiponectin in insulin resistance in PCOS women. MATERIALS AND METHODS: Forty-seven patients with PCOS and 23 control subjects, matched for age and body mass index (BMI), were enrolled in the study. Clinical, metabolic and hormonal parameters and adiponectin levels were measured, and HOMA-IR score (homeostasis model assessment-insulin resistance index) was calculated for each subject. RESULTS: There was no difference in adiponectin levels between PCOS patients and the control group. However, adiponectin levels were negatively correlated with obesity-associated parameters and HOMA-IR score in PCOS patients and controls. As adiponectin is modulated by BMI we adjusted for BMI among the PCOS patients, and found a negative correlation between adiponectin levels and HOMA-IR score (r = -0.51, p < 0.001). Adiponectin and BMI were independent determinants of insulin resistance in PCOS patients (adjusted R2 = 0.66, p < 0.001). CONCLUSION: Adiponectin did not seem to be actively involved in the pathogenesis of PCOS. However, adiponectin levels were independently associated with insulin resistance in PCOS patients, suggesting that adiponectin might play a role in the complicated metabolic abnormalities of PCOS.

Adiponectin↗

PubMed1998

Acute insulin response to intravenous glucagon in polycystic ovary syndrome.

In order to evaluate the acute insulin response after i.v. injection of glucagon in polycystic ovary syndrome (PCOS), 35 women affected by PCOS and 11 normo-ovulatory controls underwent a 75 g oral glucose tolerance test (OGTT) and, 2 days later, a glucagon test (1 mg i.v.). Patients were analysed according to their degree of obesity; the insulin release after glucagon injection for lean PCOS subjects and control women was not statistically significantly different. Conversely obese PCOS patients had higher insulin secretion after both i.v. glucagon and OGTT when compared to the other groups. Moreover the insulin secretory patterns were heterogeneously represented in lean and obese PCOS women. When the patients were analysed according to their insulinaemic response to OGTT, normoinsulinaemic PCOS women and control subjects had a similar insulin response to i.v. glucagon whereas the hyperinsulinaemic PCOS group had a higher insulin response (P < 0.0001). Moreover, a highly significant relationship was found between the insulin response to OGTT and to glucagon administration in the PCOS population (P < 0.0001; r = 0.73), which was maintained also after controlling for obesity. Our results are consistent with the hypothesis that PCOS patients could have an insulin hyper-response to glucagon administration, that is partially independent from obesity and related to their insulinaemic status. Moreover, the glucagon test could represent an effective alternative to OGTT in screening insulin disorders of PCOS patients (at least in the absence of other risk factors), due to its reliability, simplicity, and speed of performance.

Administration, Oral↗

PubMed2001

Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome.

BACKGROUND: Activin promotes ovarian follicular development, inhibits androgen production and increases FSH and insulin secretion. Follistatin, an activin-binding protein, neutralizes activin bioactivity. Therefore, a decrease in the ratio of activin/follistatin might encourage characteristic features of polycystic ovary syndrome (PCOS). We investigated whether women with PCOS showed disordered follistatin and/or activin serum concentrations. METHODS: The study group included 24 obese and 20 non-obese (body mass index vertical line and <27 kg/m2 respectively) clomiphene-failure PCOS patients. The control group included 16 obese and 46 non-obese patients with normal ovulatory cycles. Blood samples were obtained from the patients on day 3-5 of a progesterone-induced or spontaneous cycle and were assayed for LH, FSH, testosterone, 17-hydroxy-progesterone, androstenedione, follistatin, activin A, fasting glucose and insulin. RESULTS: Follistatin concentrations were comparable between obese and non-obese PCOS patients (mean +/- SE; 1171 +/- 103 and 1045 +/- 159 pg/ml respectively) and significantly higher than their respective controls (628 +/- 61 and 592 +/- 49 pg/ml, P < 0.0001 and P < 0.02 respectively). Activin A concentrations were comparable between the four groups (590 +/- 35, 513 +/- 74, 661 +/- 87 and 595 +/- 43 pg/ml in obese and non-obese PCOS and controls respectively). Stepwise regression analyses for relationships between follistatin or activin A levels and all other variables indicated that follistatin was significantly and independently positively affected by PCOS (P < 0.0001), age (P < 0.02), androstenedione (P < 0.03) and weight (P < 0.05). Activin A was significantly and independently negatively affected by PCOS (P < 0.003) and FSH (P < 0.03), and positively affected by weight (P < 0.009) and androstenedione (P < 0.02). CONCLUSIONS: Serum follistatin is increased in PCOS patients, regardless of obesity. PCOS is the most significant variable that relates to high follistatin and low activin A serum concentration. A high follistatin/activin ratio could well contribute to the pathophysiology of PCOS.

17-alpha-Hydroxyprogesterone↗

PubMed2001

Leptin concentrations in hirsute women with polycystic ovary syndrome or idiopathic hirsutism: influence on LH and relationship with hormonal, metabolic, and anthropometric measurements.

BACKGROUND: The known association between leptin, obesity and insulin action suggests that leptin may have a role in polycystic ovarian syndrome (PCOS) but this has only been addressed peripherally. METHODS: We assessed the influence of leptin on LH and investigated the relationship between leptin and body mass index (BMI), waist:hip ratio (WHR), androgen concentrations, fasting insulin and insulin:glucose ratio (IGR) in 27 women with PCOS and in 20 age- and weight-matched women with regular, ovulatory menstrual cycles and idiopathic hirsutism (IH). RESULTS: Leptin concentrations were significantly higher in obese PCOS women than in normal weight women with either PCOS or IH (P = 0.0028), but did not differ between obese women with PCOS and IH. WHR, insulin concentrations and IGR were significantly higher in obese PCOS patients in comparison with the three other groups. In IH patients, the association between leptin concentrations and WHR was lost after adjustment for BMI. In PCOS patients, a significant correlation was observed between leptin and fasting insulin concentrations, IGR, WHR and LH. After adjustment for BMI, only the correlation with LH remained significant. A stepwise regression model was set up with LH as the dependent variable to test the hypothesis that the concentrations of leptin might be modulating the concentrations of LH in PCOS patients. The relationship of LH concentrations with IGR was found to be BMI dependent. In contrast, leptin concentrations contributed negatively and significantly to LH concentrations, independently of either BMI or IGR. CONCLUSIONS: We speculate that the known attenuation in basal or stimulated response of LH in obese PCOS patients might be related to leptin resistance, which could influence LH hypersecretion. In IH ovulatory patients, normal LH concentrations suggest the presence of preserved regulatory mechanisms of GnRH pulsatility. Further studies are needed to specifically investigate the proposed correlation between leptin and GnRH modulation in PCOS.

Adolescent↗

PubMed2002

Polycystic ovarian syndrome and thrombophilia.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is associated with insulin-induced plasminogen activator inhibitor-1 (PAI-1) elevations. Since thrombophilic states correlate with high miscariage rates, as does PCOS, this study aimed at looking for thrombophilic predisposition in PCOS women compared with non-PCOS controls. METHODS: The prevalence of antithrombin III, protein S and protein C deficiencies, as well as factor V Leiden, prothrombin G20210A factor and methylene tetrahydrofolate reductase (MTHFR) mutations, was compared between two different groups of women, one with PCOS (n = 30) and one without PCOS (n = 45). RESULTS: Median proportions of activated protein C, S and antithrombin III as well as the activated protein C ratios were within normal ranges in both samples. There was no evidence that the genetic analysis for factor V Leiden or prothrombin factor differed between the two samples. The odds ratio (OR) of bearing a mutation on the MTHFR gene was 1.2-fold higher [95% confidence interval (CI) 0.470-3.065] in women with PCOS than in women without (P = 0.83). Although this difference is not statistically significant, it might indicate a slightly higher prevalence of heterozygous genotypes in women with PCOS (OR = 1.197, 95% CI 0.473-3.034). CONCLUSIONS: Molecular risk factors of hereditary thrombophilia do not show increased prevalence in women with PCOS in comparison with women in the general population. The existence of a possible trend towards higher prevalence of MTHFR mutation in women with PCOS needs further study, particularly regarding homocysteine levels.

Adult↗

PubMed2005

Birth weight in offspring of mothers with polycystic ovarian syndrome.

BACKGROUND: A relationship between reduced fetal growth and the polycystic ovary syndrome (PCOS) has been proposed in girls with PCOS. However, the birth weight in the offspring of PCOS mothers has not been systematically investigated. The aim of this study was to establish the birth weight of newborns of mothers with PCOS and to compare it with a control group of newborns of normal women matched by age and weight at the beginning of pregnancy. METHODS: The birth weight of 47 infants born from singleton pregnancies in women with well-documented PCOS was compared with 180 infants born from singleton pregnancies in healthy controls. RESULTS: The prevalence of small for gestational age (SGA) infants was significantly higher in the PCOS group compared to the control group (12. 8% versus 2.8%, respectively, P<0.02). Moreover, SGA infants born to PCOS mothers were smaller than those born to control mothers (P<0.05). The prevalence of large for gestational age infants (LGA) was similar in both groups, but birth length of LGA newborns was greater in PCOS women than controls (P<0.05). CONCLUSIONS: PCOS mothers showed a significantly higher prevalence of SGA newborns which cannot be completely attributed to pregnancy complications, and seems to be more related to the PCOS condition of the mother.

Adult↗

PubMed2005

A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome.

This meta-analysis was conducted to compare outcomes of conventional IVF in women presenting with polycystic ovary syndrome (PCOS) and non-PCOS patients. Studies in which PCOS patients undergoing IVF were compared with a matched--no male factor--control group were considered for this review. A definition consistent with the Rotterdam consensus criteria of PCOS was required, and all patients within a given study had to be treated with the same ovarian stimulation protocol. Information regarding patient characteristics and pregnancy outcome was also required. Nine out of 290 identified studies reporting data on 458 PCOS patients (793 cycles) and 694 matched controls (1116 cycles) fulfilled these inclusion criteria. PCOS patients demonstrated a significantly reduced chance of oocyte retrieval per started cycle, odds ratio (OR) = 0.5 [95% confidence interval (CI) = 0.2-1.0]. However, no difference was observed in chance of embryo transfer per oocyte retrieval between the groups (OR = 0.7, 95% CI = 0.4-1.3). Significantly more oocytes per retrieval were obtained in PCOS patients compared with controls [random effects estimate 3.4 [95% (CI) = 1.7-5.1)]. The number of oocytes fertilized did not differ significantly between PCOS patients and controls, weighted mean difference (WMD) 0.1 oocytes (95% CI = 21.4-1.6). No significant difference was observed in the clinical pregnancy rates per started cycle, OR = 1.0 (95% CI = 0.8-1.3). The incidence of ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval was rarely reported. This meta-analysis demonstrates an increased cancellation rate, but more oocytes retrieved per retrieval and a lower fertilization rate in PCOS undergoing IVF. Overall, PCOS and control patients achieved similar pregnancy and live birth rates per cycle.

Female↗

PubMed1992

The role of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) in the pathogenesis of polycystic ovary syndrome.

The objective of this study was to elucidate the relationship and role of insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), insulin and luteinizing hormone (LH) in the pathogenesis of polycystic ovary syndrome (PCOS). In a pilot study, serum concentrations of IGF-1 were determined in women with PCOS (n = 10), hypopituitarism (n = 12) and normal controls (n = 10). In the main study, serum concentrations of IGF-1, IGFBP-1, insulin and LH in women with anovulation associated (n = 23) and not associated (n = 47) with PCOS were determined. Serum concentrations of IGF-1 were not different in women with PCOS, anovulatory non-PCOS and healthy women but were low in those with hypopituitarism. Mean serum IGFBP-1 in PCOS (33.8 +/- 21.2 micrograms/l) was decreased compared with anovulatory non-PCOS (60.0 +/- 22 micrograms/l) (P = 0.0001), and correlated negatively with insulin concentrations (r = -0.67, P = 0.0006). Patients with PCOS could be separated into those with high LH and those with high insulin levels. It was concluded that women with PCOS have normal serum IGF-1 concentrations but IGFBP-1 levels, regulated by insulin, are low. Hyperinsulinaemia and raised LH are independently capable of stimulating ovarian androgen production. Growth factors may have an important role in the pathogenesis of PCOS.

Adult↗

PubMed1993

Hyperinsulinaemia in the polycystic ovary syndrome confirmed with a specific immunoradiometric assay for insulin.

OBJECTIVE: Hyperinsulinaemia in the polycystic ovary syndrome (PCOS) has previously been defined using polyclonal radioimmunoassays (RIA) in which partially processed insulin-like molecules cross-react. This study aimed to reassess hyperinsulinaemia in women with PCOS using specific immunoradiometric assays (IRMA) for insulin, proinsulin and 32-33 split proinsulin. DESIGN: Patients attended for 75 g oral glucose tolerance tests and were divided into groups depending on their degree of obesity and fasting insulin status determined by RIA. IRMA measurements for insulin-like molecules in plasma from patients with PCOS and controls were compared. PATIENTS: Thirty-four patients with ultrasound diagnosed PCOS presented to a reproductive endocrinology clinic. A control group comprised women with normal ovaries on ultrasound. Four groups were constructed, two with normal fasting insulin concentrations (lean PCOS and controls) and two with hyperinsulinaemia (lean and obese PCOS). MEASUREMENTS: Plasma glucose, insulin (RIA and IRMA), proinsulin and 32-33 split proinsulin concentrations were measured at time 0, 30 and 120 minutes of an oral glucose tolerance test. RESULTS: Hyperinsulinaemia determined by RIA in lean and obese women with PCOS was confirmed using a specific IRMA assay for insulin. Plasma proinsulin and 32-33 split proinsulin concentrations were higher in hyperinsulinaemic women with PCOS compared with women with normal insulin concentrations. The proportion of circulating insulin-like molecules represented by proinsulin and 32-33 split proinsulin was similar in all groups studied. CONCLUSIONS: Hyperinsulinaemia in PCOS is likely to reflect insulin resistance because the raised concentrations of proinsulin and 32-33 split proinsulin were in proportion to the raised insulin concentrations. Hyperinsulinaemia in PCOS, defined by RIA, therefore differs from that in non-insulin dependent diabetes mellitus where it is largely accounted for by disproportionate hyperproinsulinaemia.

Blood Glucose↗

PubMed1995

Diurnal variation of sex hormone binding globulin and insulin-like growth factor binding protein-1 in women with polycystic ovary syndrome.

OBJECTIVES: The aim of this study was to examine (1) the diurnal variation in SHBG and (2) the inter-relationships of insulin, IGF-I, SHBG and IGFBP-1 over 24 hours in 10 women with anovulatory PCOS and compare them with weight-matched ovulatory controls. PATIENTS AND METHODS: The two groups comprised 10 anovulatory women with PCOS (as defined by clinical, ultrasound and biochemical criteria) and 10 weight matched controls. Serum samples were taken at two-hourly intervals for 24 hours and stored for measurement of SHBG, IGFBP-1, insulin and IGF-I. Differences between the groups were compared using the Wilcoxon ranked paired tests of the individual peak and trough concentrations in each group. The variation in insulin, IGFBP-1 and SHBG concentrations over 24 hours was tested using two-way analysis of variance with the factors time and subject. Spearman's correlation coefficient was calculated from the subjects' median value over 24 hours. RESULTS: The median (interquartile range) body mass index (BMI) was 25.2 (22.2-29.3) in the PCOS group and 24.3 (23.2-25.7) kg/m2 in the control group. Serum testosterone (T) and LH levels were significantly raised in the PCOS group compared to the control group; T 3.8 (2.9-5.6) vs 1.9 (1.9-2.5) nmol/l (P < 0.007) and LH 12 (10-15) vs 4.1 (3.6-4.5) IU/I (P < 0.005) respectively. There was no diurnal variation in SHBG. The median (interquartile ranges) of the peak SHBG concentrations was lower in the PCOS group: 29.4 (14.9-39.4) vs 52.1 (39.4-61) nmol/l in the control group (P < 0.01). The fasting levels of insulin at 0600 h (median (interquartile ranges)) were not significantly different between the groups; 6.6 (5.4-9.8) and 6.2 (1.9-7.6) mU/l, respectively, although the peak median concentrations were significantly different; PCOS 66.1 (50.9-129.2) vs 40 (36.1-74.2) mU/l (P < 0.05). Two-way analysis of variance showed a diurnal variation in insulin concentrations in the control group (P = 0.001) but not in the PCOS group (P = 0.1). The diurnal variation in IGFBP-1 was similar in the two groups but the peak median levels were lower in the women with PCOS 54.9 (22.3-79.2) vs 71.5 (60.5-99.3) micrograms/l (P < 0.03). The decline in IGFBP-1 concentrations correlated with the increase in insulin concentrations. The IGF-I concentrations were similar in the two groups. There was a significant negative correlation between SHBG and insulin (P < 0.05) and between insulin and IGFBP-1 (P < 0.01). CONCLUSION: This study demonstrates that there is no diurnal variation in SHBG concentrations and confirms the finding of a marked diurnal variation in the concentration of IGFBP-1. Women with PCOS who are anovulatory have an abnormal pattern of insulin secretion with an absence of diurnal variation compared to weight matched controls. This provides further evidence of the relative insulin resistance which is independent of weight found in women with anovulatory PCOS. The inverse correlations of insulin concentrations with SHBG and IGFBP-1 support the role of insulin as a possible regulator of the circulating levels of these binding proteins although the difference in the time course of their response makes it unlikely that they are co-regulated.

Circadian Rhythm↗