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Polycystic ovary syndrome and type 2 diabetes mellitus.

Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple specialists together. Gynecologists, endocrinologists, cardiologists, pediatricians, and dermatologists are all concerned with PCOS patients and share research data and design clinical trials to learn more about the syndrome. Insulin resistance is a common feature of PCOS and is more marked in obese women, suggesting that PCOS and obesity have a synergistic effect on the magnitude of the insulin disorder. It leads to increased insulin secretion by beta-cells and compensatory hyperinsulinemia. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism and metabolic disturbances. If beta-cell compensatory response declines, relative or absolute insulin insufficiency develops which may lead to glucose intolerance and type 2 diabetes. Moreover, insulin resistance in PCOS may be considered a risk factor for gestational diabetes (GD).

Adult↗

Are NHS primary care performance indicator scores acceptable as markers of general practitioner quality?

BACKGROUND: In 2002 the Department of Health published a list of 20 indicators to judge the performance of the 302 primary care organisations (PCOs) in England during 2001-2002. General practitioners (GPs) have expressed doubts about the relevance, applicability and evidence base of these indicators for actual practice. AIMS: To fashion NHS performance indicators to be acceptable and relevant to practicing GPs. DESIGN OF STUDY: A Delphi technique followed by simple mathematical modelling. METHODS: We asked a group of 24 senior GP educators to place the Department of Health performance indicators in rank order as markers of quality in general practice. We found just seven indicators comprised 73% of the markers chosen and all seven were chosen by over three-quarters of the responders. Using a simple 'sign test' system, we then calculated a composite points score for all 302 PCOs. RESULTS: We found that there were almost twice as many PCOs at the upper and lower ends of performance and fewer in the middle than we predicted theoretically. The results suggest that pan-PCO or practice factors account for the low performance scores of 16 of 35 PCOs with extremely poor performance and for the high scores of 17 of the 36 PCOs with extremely high performance. CONCLUSION: We have developed a method that shows how numerous Department of Health performance indicators can be merged into a single composite performance score. We show that this composite performance score is easy to derive, simple to interpret, is acceptable to GPs, and has face validity.

Attitude of Health Personnel↗

[Ultrasound criterion for the diagnosis of polycystic ovary syndrome: ovarian stroma/total area ratio].

OBJECTIVE: To evaluate the diagnostic value of ultrasound parameters of ovarian stroma area (S), total ovarian area (A) and S/A ratio for polycystic ovarian syndrome (PCOS). METHODS: The A, S and S/A ratio were determined by use of transvaginal pelvic ultrasound, and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) were assayed in 58 PCOS patients and 60 controls. Of 58 PCOS patients, 32 underwent hyperinsulinemic euglycemic clamp technique (HGCT). RESULTS: Patients with PCOS showed significantly higher ovarian S and S/A ratio when compared to the control groups (P = 0.045, P = 0.001, respectively). S/A ratio and S were significantly related to HGCT results and T. CONCLUSION: The S/A ratio and S are of value in diagnosis of PCOS.

Adult↗

[Study on the (TAAAA)n repeat polymorphism in sex hormone-binding globulin gene and the SHBG serum levels in putative association with the glucose metabolic status of Chinese patients suffering from polycystic ovarian syndrome in Shandong province].

OBJECTIVE: To investigate the relationship of (TAAAA)n repeat polymorphism in the promoter of the sex hormone-binding globulin (SHBG) gene and SHBG serum levels to the glucose metabolic status of Chinese polycystic ovary syndrome (PCOS) patients in Shandong province. METHODS: GeneScan method was used to detect and identify (TAAAA)n repeat number (alleles) and genotypes for 156 controls and 157 patients who were divided into normal glucose tolerance without hyperinsulinemia (NIR group) and with hyperinsulinemia (HI group) and abnormal glucose metabolic (AGM) group according to the results of oral glucose test and insulin resistant test; IRMA was used to measure serum SHBG for part of them. RESULTS: Five alleles containing (TAAAA) 6-10 repeats and 14 genotypes including 6/6, 6/7, 6/8, 6/9, 6/10, 7/7, 7/8, 7/9, 7/10, 8/8, 8/9, 8/10, 9/9, 9/10 repeats genotypes were present in the subjects. Genotype distribution of 6/10 repeats genotype is lower in PCOS than that in control, and 8/9 repeats genotype vice versa (P < 0.01); among PCOS subgroups, the eight repeat genotypes in NIR group is more frequent than that in HI group (P < 0.01), and 7/9 genotype distribution in AGM group is higher than that in NIR group and HI group(P < 0.05-0.01). The serum SHBG levels in homozygous genotype groups exhibit a sequence of 8/8 > 9/9 > 6/6, 7/7 repeats and the fall of serum SHBG trend is in reversed relation with the increase in body mass index (BMI), Homa-IR, and blood pressure. Serum SHBG levels in AGM exhibit a sequence of HI group < NIR group < control but show no statistical difference between both groups. CONCLUSION: This study reveals that the repeat number, alleles, genotypes and their distributions in Chinese women are very different from these in foreigners. Some special genotypes and low serum SHBG levels may be associated with PCOS and its glucose metabolic status; some special genotypes may influence Chinese serum SHBG and need more studies, but both SHBG gene polymorphism genotype and serum SHBG are not good indicators to find out the PCOS individual at high risk.

Adult↗

Subclinical eating disorder, polycystic ovary syndrome- is there any connection between these two conditions through leptin- a twin study.

The genetic property of subclinical eating behaviour (SEB) and the link between SEB and polycystic ovary syndrome (PCOS) has been studied before but the role of leptin within this connection has never been investigated. The objective of this study was 1). to study the genetic property of SEB. 2). To find a link between leptin, SEB and PCOS. One hundred and fifty four (77 pairs) female-female Iranian twins including 96 MZ individuals (48 pairs) and 58 DZ individuals (29 pairs) participated in the study. Clinical, biochemical and ultrasound tools were used to diagnose polycystic ovary syndrome. BITE questionnaire was filled out for subjects. Eight percent of subjects were diagnosed for subclinical eating disorder. No significant difference was found between intraclass correlation of MZ and DZ (z = 0.57, P = 0.569). Serum leptin level correlated significantly with bulimia score (P < 0.007). The mean (+/-SD) value for bulimia score was found to be higher among PCOS(positive) subjects (3.27 +/- 5.51) in comparison with PCOS(negative) subjects (2.06 +/- 4.48) (P < 0.001). The genetic property of subclinical eating disorder was not confirmed as shared environment might have played a major role in likeliness of DZ twins as well as MZ. Leptin is linked with both subclinical eating disorder and PCOS.

Adult↗

[Evaluation of dopaminergic activity of the hypothalamus in patients with polycystic ovarian syndrome].

To evaluate the hypothalamic dopaminergic activity in patients with polycystic ovary syndrome (PCOS), we studied the PRL, TSH, LH and FSH responses to i.m. administration of sulpiride in five euthyroid women affected by PCOS and in five normal women. The mean basal PRL and TSH plasma levels resulted significantly higher (p less than 0.01) in PCOS subjects with respect to normal subjects. The incremental area under PRL and TSH profiles, after sulpiride administration, were significantly lower (p less than 0.05) in PCOS patients than in the control group; no significant variation of LH and FSH plasma levels resulted. Our data suggest a decrease dopaminergic activity in PCOS.

Dopamine Agents↗

Update on the management of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects 5% to 10% of women in reproductive age. It is the most simply defined as the association of hyperandrogenism (diagnosed clinically and/or biochemically) with chronic anovulation in the absence of specific ovarian, adrenal and pituitary gland diseases. Recent studies have revealed that PCOS is associated with hyperinsulinemia and insulin resistance. Both of them have been shown to play a substantial role in the increased risk of the cardiovascular events. The new data concerning the pathogenesis and management of PCOS have changed its treatment strategy. The management of PCOS is complex and includes lifestyle modification combined with dietary-induced weight loss, oral contraceptives, clomiphene citrate, gonadotropins, antiandrogens and insulin-sensitizing agents. Women with PCOS, diagnosed and managed properly, can benefit from the reduction or even reversal of the reproductive and metabolic morbidities and from the reduction of the risk factors for cardiovascular disorders. In this article, we describe all these treatment options. Although both standard and novel therapies are discussed, this review focuses on the progress made in the recent years.

Female↗

[Quality of life in women with polycystic ovary syndrome].

OBJECTIVE: To evaluate the Quality of life (QOL) in women with Polycystic ovary syndrome (PCOS) and to compare it with that of healthy controls. METHODS: This is a comparative study including 60 women - 30 with PCOS and 30 healthy controls. After calculating body mass index (BMI) all participants filled translated in bulgarian version of Health-related Quality of life Questionnaire (PCOSQ). The questionnaire includes 26 items from five domains - weight, hair, menstruation, infertility and emotions. RESULTS: Our study confirms the negative impact of PCOS on QOL. The decrease includes all 5 domains of PCOSQ. The most significant is decrease in weight domain with 45, 1% in comparison with controls, followed by hair and emotions. Cronbach's a coefficient that determines the internal consistency of a scale was 0,86 which means excellent reliability. CONCLUSION: PCOS has a negative impact on QOL. The Bulgarian version of PCOSQ is a reliable instrument for measuring QOL in women with PCOS.

Adolescent↗

The value of prolactin dynamics as a predictor of ovulation with bromocriptine in patients with polycystic ovary syndrome.

Six euprolactinemic polycystic ovary syndrome (PCOS) patients were subjected to a 24-hour study with serum sampling every 30 minutes and a perphenazine stimulation test. The serum prolactin (PRL) levels were compared with those of five healthy normoprolactinemic women whose cases were evaluated in a similar fashion. In addition to evaluating the PRL secretory pattern and lactotroph response, the PCOS individuals were given dopamine agonist therapy in a graduated dosage schedule, increasing each month, over a 3-month interval. The PCOS patients exhibited parallel but lower PRL levels than the control subjects during the late evening and early morning hours (P less than 0.0001) and were less responsive to perphenazine at the 6-hour sampling (P less than 0.05). Only one PCOS individual had suggestive evidence of ovulation over the 15 cycles the group was monitored. Therefore, we conclude that euprolactinemic PCOS patients who are nocturnal hyposecretors of PRL and who hyporespond to a perphenazine stimulation test are not likely to ovulate on bromocriptine in the dosages used in this study.

Adult↗

A twin study of polycystic ovary syndrome.

OBJECTIVE: To examine the role of genetic and environmental factors in polycystic ovary syndrome (PCOS) by using the classic twin model. SETTING: Outpatient clinic of the Royal Hospital for Women, Paddington, Sydney, New South Wales, Australia. PATIENTS: A group of 19 monozygotic (MZ) and 15 dizygotic (DZ) twin pairs identified from the national twin register. INTERVENTIONS: Ultrasound, clinical, and biochemical parameters were used to define PCOS. RESULTS: Eleven pairs of twins (5 MZ, 6 DZ pairs) were scan-discordant (i.e., one twin had scan-PCOS and the co-twin did not). Model-fitting analysis suggested that fasting insulin level, androstanediol glucuronide, and body mass index (BMI) were significantly influenced by genetic factors. CONCLUSION: This study suggests that PCOS is not the result of a single autosomal genetic defect, but rather environmental factors, perhaps both intrauterine and extrauterine, are involved in the pathogenesis of this disorder or that PCOS may be an X-linked disorder or the result of polygenic factors. However, fasting insulin level, androstanediol glucuronide, and BMI did appear to be under significant genetic influence.

Adolescent↗

[Responses of somatostatin, beta-endorphin and dynorphin A to A glucose load in two groups of women with polycystic ovarian syndrome].

OBJECTIVES: To investigate the relationship between elevated luteinizing hormone (LH), hyperinsulinemia and neuropeptides in patients with polycystic ovarian syndrome (PCOS). METHODS: An oral glucose (100g) tolerance test (OGTT) was performed in 15 normally menstruating women (control) and 30 PCOS women with LH/follicle stimulating hormone (FSH) ratio greater than 3 (group 1) and 25 PCOS subjects with the ratio < 3 (group 2). The responses of insulin, somatostatin (SS), beta-endorphin (beta-EP) and dynorphin A (Dyn A) during OGTT were measured by RIA. RESULTS: In basal state, significant negative correlations were found between LH and SS (r = -0.51, P < 0.05) in group 1 and between LH and beta-EP (r = -0.49, P < 0.05) in group 2. During OGTT, PCOS women had a greater beta-EP and Dyn A responses in group 1 and an impaired SS response in group 2 as compared with the control. CONCLUSION: These data suggested lower endogenous SS, higher beta-EP and Dyn A may lead to elevation of LH and insulin secretions in patients with PCOS.

Adult↗

Endometriosis and polycystic ovary syndrome: enhanced stimulatory effect of peritoneal fluid on progesterone release from human granulosa-lutein cells.

OBJECTIVE: To compare the activity of peritoneal fluid (PF) from women with and without endometriosis or polycystic ovary syndrome (PCOS) on P release from cultured human granulosa-lutein cells. DESIGN: Case-control study. SETTING: Medical school and hospital. PATIENTS: Women with mild to moderate endometriosis or PCOS and controls undergoing laparoscopic sterilizations. MAIN OUTCOME MEASURES: Human granulosa-lutein cells, obtained from the IVF clinic, were cultured with increasing volumes of steroid-extracted PF samples with and without hCG. Progesterone concentrations in the media after 72 hours culture were measured by RIA. RESULTS: Peritoneal fluid stimulated P release in a dose-dependent manner and, at the highest dose, the response was enhanced significantly by PF from women with endometriosis and PCOS compared with control samples. The effects of PF plus hCG were not simply additive. There was a large potentiation of the response, which was greater in women with endometriosis and PCOS. CONCLUSIONS: Peritoneal fluid contains factors that stimulate P release and potentiate the response to hCG. The increased activity of PF associated with endometriosis and PCOS in part may have some significance in abnormal ovarian function associated with these syndromes.

Adult↗

Management of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), also known as Stein-Leventhal Syndrome, is a condition that afflicts many women during their childbearing years. It is one of the leading causes of female infertility. Symptoms of PCOS are related to androgen excess and are not associated with estrogen deficiency. Classic symptoms include amenorrhea, hirsutism, acne, and obesity. Management of PCOS is directed by the client's concerns regarding symptoms, desire for pregnancy, and degree of morbidity related to androgen excess. First-line management of PCOS includes diet modification, weight loss, and stress management. First-line treatment for androgen excess is estrogen therapy, the combination of estrogen and progesterone being the drugs of choice. Uncomplicated amenorrhea in PCOS is managed with monthly or bimonthly administration of medroxyprogesterone. The antiestrogen clomiphene citrate has been the drug of choice for inducing ovulation. The success of any treatment plan will depend largely on the client's ability to reduce body weight.

Androgen Antagonists↗

[The polycystic ovary syndrome and insulin resistance].

The insulin resistance syndrome and the polycystic ovary syndrome (PCOS) appear to have some following coincidences: the existence of subclinical acanthosis nigricans in PCOS hyperinsulinemic women, correlation of insulin levels and free testosterone, insulin-like growth factor I binding protein (IGFIBP), and sex-hormone binding globulin. Insulin and IGFI act synergically with luteinizing hormone increasing the activity of cytochrome P450c17 and its enzymatic activity in the adrenals. The decrease in IGFI level and IGFI receptors in the ovarian granulosa cells reduce the steroids aromatisation. The increased expression of IGFI receptors in the theca cells favours the androgens' synthesis. Long-term insulin therapy results in an increase in ovary volume and the blood androgens levels. The deterioration of insulin resistance in PSOC women progresses also by the reduction of type I of skeletal muscle fibres which are sensitive to insulin, and the increase of type II fibres which are resistant to insulin in hyperandrogenemia. Testosterone deteriorates the skeletal as well as hepatic insulin sensitivity by both its facilitating effect on lipolysis and the increase of free fatty acids. Abdominal obesity seen in PCOS and insulin resistance is composed by adipocytes with glucocorticoid receptors, which after cortisol stimulation activate the lipoprotein lipase and fat accumulation. Gynoid obesity with the preferential aromatisation of steroids is not evolved because of the low estrogens and progesterone levels in PCOS. Low progesterone levels (with anticortisol effect) support the development of abdominal obesity. Ultimately, the early peak of insulin secretion (4-8 min) in PCOS is higher. This fact should testify a certain diabetic disposition. (Ref. 37.)

Female↗

Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in these women. Although ovulation and pregnancy have been achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been clearly demonstrated. OBJECTIVES: To assess the effectiveness of pulsatile GnRH administration in women with polycystic ovary syndrome (PCOS), in terms of ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched 13 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: All relevant published randomised clinical trials were selected for inclusion if treatment consisted of pulsatile GnRH administration versus another treatment for ovulation induction in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. All trials were screened and analysed for predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto method. MAIN RESULTS: Four randomised clinical trials involving 57 women were identified comparing four different treatments: GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus clomiphene citrate. This means that there was only one trial in any one comparison. In two studies, data of pre- and post-crossover were not described separately. All trials were small and of too short duration to show any significant differences in pregnancy results. The odds ratio for ongoing pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation syndrome was seen only in women allocated to ovulation induction with HMG. REVIEWER'S CONCLUSIONS: The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Female↗

Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis.

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). Increased levels of reactive oxygen species (ROS) derived from infiltrating macrophages and microglial cells have been shown to reduce the levels of endogenous antioxidants and to cause the oxidation of various substrates within the MS plaque. To determine whether oxidative damage takes place beyond visible MS plaques, the occurrence of total carbonyls (TCOs) and protein carbonyls (PCOs) in the normal-appearing white matter (NAWM) and gray matter (NAGM) of eight MS brains was assessed and compared with those of four control brains. The data show that most (7/8) of the MS-WM samples contain increased amounts of PCOs as determined by reaction with 2,4-dinitrophenylhydrazine and Western blot analysis. These samples also have high levels of glial fibrilary acidic protein (GFAP), suggesting that oxidative damage is related to the presence of small lesions. In contrast, we detected no evidence of protein thiolation (glutathionylation and cysteinylation) in the diseased tissue. To our surprise, MS-NAGM specimens with high GFAP content also showed three times the concentration of TCOs and PCOs as the controls. The increase in PCOs is likely to be a consequence of reduced levels of antioxidants, in that the concentration of nonprotein thiols in both MS-WM and -GM decreased by 30%. Overall, our data support the current view that both NAWM and -GM from MS brains contain considerable biochemical alterations. The involvement of GM in MS was also supported by the decrease in the levels of neurofilament light protein in all the specimens analyzed. To the best of our knowledge, this is the first study demonstrating the presence of increased protein carbonylation in post-mortem WM and GM tissue of MS patients.

Blotting, Western↗

Acute depletion of reduced glutathione causes extensive carbonylation of rat brain proteins.

This study was aimed at establishing whether oxidative stress induced by acute depletion of brain glutathione (GSH) is sufficient to generate protein carbonyls (PCOs). To this end, rat brain slices were incubated separately with the GSH depletors 1,3-bis[2-chloroethyl]-1-nitrosourea (BCNU) and diethyl maleate (DEM), and protein carbonylation was assessed on Western blots after derivatization with dinitrophenyl hydrazine. Incubation with 1 mM BCNU or 10 mM DEM for 2 hr decreased GSH levels by > 70%. Under these conditions the carbonylation of several proteins (40-120 kDa) increased by 2-3 fold. Isolation of carbonylated proteins showed that augmented PCOs represents a rise in the amount of oxidized protein. The iron chelator deferoxamine, the superoxide scavenger rutin and the H2O2 quencher dimethylthiourea all prevented DEM-induced protein carbonylation and lipid peroxidation (TBARS), indicating that the underlying mechanism involves the iron-catalyzed generation of hydroxyl radicals from H(2)O(2) (Fenton reaction). Inhibition of catalase activity with sodium azide and aminotriazole, and glutathione peroxidase activity with mercaptosuccinic acid did not increase PCOs or TBARS, suggesting that increased production of reactive oxygen species (ROS) rather than compromised cellular antioxidant defenses is the cause for the accumulation of H2O2 after GSH depletion. PCO formation was not affected by the xanthine oxidase inhibitor oxypurinol but it was reduced by SKF-525A and carbonyl cyanide 3-chlorophenylhydrazone, indicating that the microsomal monooxygenase system and the mitochondrial electron transport system are the major sources of ROS. Consistent with these findings, subcellular fractionation studies showed that mitochondria and synaptosomes are the major PCO-containing organelles. These results were also supported by the anatomic distribution of PCOs in brain. Our observations may be important in the context of multiple sclerosis where decreased GSH, mitochondrial dysfunction, excessive production of ROS, and increased protein carbonylation have all been reported.

Animals↗

Hyperinsulinemia in polycystic ovary syndrome: relationship to clinical and hormonal factors.

We analyzed the association between hyperandrogenism and hyperinsulinemia, and their relationship to body mass index, in a large series of patients with polycystic ovary syndrome (PCOS). A characteristic hormonal profile was sought in women with marked hyperinsulinemia. The patient group consisted of 73 women with PCOS, ranging in age from 16 to 29 years. The control group consisted of 34 healthy women with no evidence of hyperandrogenism, aged 19-30 years. None of the patients or control women had a body mass index above 27 kg/m2. Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, sex hormone binding globulin, 17-hydroxyprogesterone, and free cortisol were determined by radioimmunoassay. The free testosterone index was calculated. The oral glucose tolerance test was used to analyze basal insulinemia, maximum insulin peak, and the insulinemia/glycemia index. In the group with PCOS body mass index was greater, free testosterone index was higher, and levels of dehydroepiandrosterone sulfate, testosterone, 17-hydroxyprogesterone (P < 0.001) and androstenedione (P < 0.05) were higher than in the control group. Of the insulin parameters, basal insulinemia, maximum insulin peak, and insulinemia/glycemia index were higher in the patient group (P < 0.001). In patients with marked insulinemia, free testosterone index was more markedly elevated, and gonadotrophin levels were normal. Our data confirm that a characteristic pattern of hyperinsulinemia is associated with PCOS. We found no causal relationship between hyperinsulinemia and androgen levels. A characteristic hormonal pattern was found in patients with marked hyperinsulinemia.

Adolescent↗