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PubMed2004

Screening for and treatment of polycystic ovary syndrome in teenagers.

Polycystic ovary syndrome (PCOS) usually arises during puberty and is marked by hyperinsulinemia and hyperandrogenism. Adolescents with PCOS are at an increased risk of developing health problems later on in life such as type 2 diabetes, cardiovascular disease, and infertility. Furthermore, the physical signs of PCOS can be detrimental to a teenage girl's self-image. Early diagnosis and treatment of PCOS in adolescents are essential in ensuring adulthood health and restoring self-esteem. Treatments for an adolescent with PCOS include diet and exercise, metformin, and oral contraceptive pills. Each of these options has been shown to be effective in improving certain aspects of PCOS, and probably the best treatment plan involves some combination of them.

Adolescent↗

PubMed2025

Association of CYP19 gene SNPs (rs7176005 and rs6493497) with polycystic ovary syndrome susceptibility in Northern Chinese women.

PURPOSE: The objective of this study was to elucidate the relationship between two single nucleotide polymorphisms (SNPs) rs7176005 and rs6493497 in CYP19 gene and the risk of polycystic ovary syndrome (PCOS) in Northern Chinese women. METHODS: In this case-control study, a total of 340 women with PCOS and 340 matched healthy controls were recruited. Polymerase chain reaction ligase detection reaction (PCR-LDR) method was used to investigate two SNPs (rs7176005 and rs6493497) in the 5'-flanking region of CYP19 gene exon 1. RESULTS: We observed a significant association of rs7176005 and rs6493497 with reduced risk of PCOS. Compared with CC genotype, a significant association of CT genotype (p = 0.019), TT genotype (p < 0.001) and combined CT + TT genotype (p < 0.001) with reduced risk of PCOS was observed. The result of linkage disequilibrium analysis showed that these two SNPs are in complete linkage disequilibrium (r2 = 1). For rs7176005 SNP, compared with CC genotype, CT, TT and CT + TT genotypes reduced the risk of PCOS. The age, BMI-adjusted OR were 0.650 (95% CI = 0.460-0.917), 0.158 (95% CI = 0.066-0.376) and 0.545(95% CI = 0.391-0.759), respectively. CONCLUSIONS: These findings highlight a significant association between CYP19 gene polymorphisms and PCOS susceptibility, implying potential protective effects of T and A alleles. Of course, the major limitation of this study is the sample size of the case-control study. Larger cohort studies are needed to confirm these findings and investigate the underlying causes.

Adult↗

PubMed2003

Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study.

Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35 microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin during a 75-g oral glucose tolerance test; early phase insulin and C-peptide secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment. Metformin did not have any effect on glucose tolerance or insulin sensitivity, but fasting insulin concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P = 0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P = 0.01), and hepatic insulin clearance increased during the treatment. Furthermore, metformin decreased serum testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2 nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any significant effect on glucose tolerance, serum insulin levels, or insulin sensitivity, but it increased slightly the body mass index (P = 0.09) and significantly serum leptin concentrations (P < 0.001) and decreased serum testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on insulin and glucose metabolism also have to be taken into consideration in nonobese subjects. Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with anovulation may also benefit from metformin treatment.

Adult↗

PubMed2003

Homocysteine levels and C677T polymorphism of methylenetetrahydrofolate reductase in women with polycystic ovary syndrome.

The aim of this study was to investigate the homocysteine (Hcy) levels and the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), a crucial factor of the Hcy metabolism in young women with polycystic ovary syndrome (PCOS). Seventy young women with PCOS and another 70 healthy women with low folate intake were enrolled. Cases and controls were matched for age, body mass index, and allele frequency. Hcy, vitamin B(12), and folate levels were measured, and a genetic analysis of 5,10-MTHFR at nucleotide 677 was performed in all subjects. No difference in mean Hcy levels was observed between PCOS women in comparison to the control group. Considering the different MTHFR polymorphism, no significant difference was found in serum Hcy levels between subjects with PCOS and controls showing CC (10.4 +/- 3.1 vs. 9.7 +/- 2.9 micromol/liter +/- SD) and CT genotypes (10.9 +/- 3.8 vs. 11.0 +/- 3.2 micromol/liter +/- SD). In subjects with a TT homozygous state, a significant (P < 0.05) difference was observed between PCOS and control women (11.5 +/- 3.9 vs. 22.0 +/- 7.8 micromol/liter +/- SD). In conclusion, our data show that in PCOS women, the serum Hcy levels are normal, and the C677T polymorphism of MTHFR does not influence the Hcy levels like in controls.

Adolescent↗

PubMed2003

Beyond adrenal and ovarian androgen generation: Increased peripheral 5 alpha-reductase activity in women with polycystic ovary syndrome.

Hyperandrogenism, a main clinical feature of polycystic ovary syndrome (PCOS), is thought to result from enhanced ovarian and adrenal androgen generation. To investigate the contribution of peripheral steroidogenesis, we used an oral challenge with dehydroepiandrosterone (DHEA) and analyzed its downstream conversion toward androgens in eight women with PCOS (age, 20-32 yr; body mass index, 20-41 kg/m(2)) and eight healthy women matched for age and body mass index. They underwent frequent serum sampling and urine collection for 8 h on three occasions: at baseline, and after 4 d of dexamethasone (Dex; 4 x 0.5 mg/d), followed by ingestion of 100 mg DHEA or placebo. Dex induced similar significant suppression of circulating steroids in both groups. The oral DHEA challenge led to similar significant increases in the area under the concentration-time curve (0-8 h after Dex) of serum DHEA, DHEA sulfate, androstenedione, and testosterone. However, after oral DHEA, PCOS women had significantly higher increases in serum 5 alpha-dihydrotestosterone (P < 0.01), its main metabolite androstanediol glucuronide (P < 0.05), and the 5 alpha-reduced urinary androgen metabolite androsterone (P < 0.05). PCOS women also had significantly higher baseline excretion of 5 alpha-reduced glucocorticoid (P < 0.01) and mineralocorticoid metabolites (P < 0.05). Taken together, these data indicate enhanced peripheral 5 alpha-reductase activity in PCOS. Thus, not only ovary and adrenal, but also liver and peripheral target tissues, significantly contribute to steroid alterations in PCOS.

Adult↗

PubMed2003

Increased luteinizing hormone secretion in women with polycystic ovary syndrome is unaltered by prolonged insulin infusion.

In PCOS women with insulin resistance, hyperinsulinemia may contribute to inappropriate gonadotropin secretion. To determine whether insulin influences gonadotropin release in PCOS, pulsatile LH secretion and gonadotropin responses to GnRH were evaluated before (phase 1) and during (phase 2) insulin infusion. In phase 1, 11 PCOS and 9 normal women on separate days underwent 1) frequent blood sampling (q 10 min) for 12 h and 2) gonadotropin stimulation by successive doses of GnRH, 2 microg, 10 microg, and 20 microg, administered i.v. at 4 h intervals over a continuous 12 h. In phase 2, studies were repeated 2 h after initiation of a 12-h hyperinsulinemic-euglycemic clamp (80 mU/m(2).min). Administration of insulin to both groups failed to alter mean serum gonadotropin concentrations, LH pulse frequency, or LH pulse amplitude. Moreover, gonadotropin responses to GnRH were unchanged by insulin infusion. In PCOS and normal women, a significant reduction of serum androstenedione was associated with insulin administration, whereas no differences were noted for the remaining androgens and estrogens measured. These findings demonstrated that in PCOS women, LH secretion and gonadotropin responses to GnRH were not influenced by insulin administration. Insulin infusion had little effect on steroid hormone production with the possible exception of androstenedione. These results suggest that inappropriate LH secretion in PCOS is not a direct consequence of insulin resistance and compensatory hyperinsulinemia.

Adult↗

PubMed2004

The hormonal phenotype of Nonclassic 3 beta-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females is associated with insulin-resistant polycystic ovary syndrome and is not a variant of inherited HSD3B2 deficiency.

To test our hypothesis that the hormonal phenotype of mild 3beta-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females (HF) is related to insulin-resistant polycystic ovary syndrome (PCOS), we compared insulin sensitivity and gonadotropin secretion in HF with compromised ( downward arrow ) adrenal HSD3B phenotype despite normal HSD3B2 genes (n = 6) to those in HF with classic PCOS (n = 9) of similar ages (14-36 yr). The same was examined in premature pubarche (PP) girls with (n = 4) and without the descending HSD3B phenotype (n = 5). The descending HSD3B phenotype was defined by ACTH-stimulated Delta(5)-precursor steroid levels and Delta(5)-precursors to Delta(4)-product steroid ratios higher than those in normal females (n = 30 for adult, n = 12 for pubertal). Classic PCOS HF had elevated testosterone levels and normal ACTH-stimulated hormonal profiles. The insulin sensitivity index determined by the frequently sampled iv glucose-tolbutamide test (FSIVGTT) in all HF with descending HSD3B phenotype and in all HF with classic PCOS, regardless of body mass index (BMI), was lower than in all eight normal BMI and five high BMI normal females. Integrated incremental insulin determined by FSIVGTT, the area under the curve for insulin, and fasting and 2 h glucose load insulin levels determined by an oral glucose tolerance test in both HF groups were higher (P < 0.01-0.0001) than those in normal females with normal or high BMI. LHRH-stimulated LH levels and LH/FSH ratios in both HF groups were higher (P < 0.01) than those in normal females. No statistical differences were found in the insulin sensitivity and gonadotropin parameter between the two PP girl groups. The insulin sensitivity index in each half of PP girls with the descending HSD3B phenotype was lower than or similar to that in control PP girls with a similar weight length index. The fasting glucose to insulin ratio in three of four PP girls with the descending HSD3B phenotype was lower than that in control PP girls, but one of four with the descending HSD3B phenotype had a higher fasting glucose to insulin ratio than the control PP girls. The findings of insulin sensitivity and gonadotropin data in both HF with the descending HSD3B phenotype and classic PCOS indicate significant insulin resistance and LH hypersecretion in both. These suggest that the descending HSD3B phenotype in HF is associated with a variant of insulin-resistant PCOS. The variable insulin sensitivity parameter in the small number of PP girls with the descending HSD3B phenotype warrants a further large scale study to examine this phenotype association with childhood insulin resistance.

3-Hydroxysteroid Dehydrogenases↗

PubMed2004

Assessment of insulin sensitivity from measurements in the fasting state and during an oral glucose tolerance test in polycystic ovary syndrome and menopausal patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) and menopausal subjects are characterized by an increased cardiovascular and type 2 diabetes mellitus risk, at least partially related to insulin disturbances. The evaluation of insulin resistance in these patients could be useful as primary prevention. The aim of the study was to verify the validity of several indexes of insulin sensitivity in PCOS and menopausal subjects by comparing the data obtained by these indexes to those of euglycemic-hyperinsulinemic clamp studies. METHODS: One hundred PCOS and 110 menopausal subjects were analyzed; all subjects underwent an oral glucose tolerance test (75 g) and euglycemic-hyperinsulinemic clamp study. Seven PCOS patients and 13 menopausal subjects had impaired glucose tolerance or type 2 diabetes mellitus and were excluded from the study. After analysis of correlation coefficients between the evaluated indexes and the clamp studies, the sensitivity and specificity of different cut-off values for each parameter were analyzed by receiver operating characteristic (ROC) curves. RESULTS: The best correlation coefficients with clamp studies were obtained with the Avignon insulin sensitivity index (SiM) (R(s) = 0.7812) in PCOS patients and the Matsuda and De Fronzo index (R(s) = 0.6178) in menopausal patients. The best predictive index of insulin resistance in PCOS was a Avignon insulin sensitivity basal index (SibB) value of 62 or less (78% sensitivity, 95% specificity) and an insulin area under the curve (AUC) of 7,000 microIU/ml or more (>/=50,225 pmol/liter) x 120 min (83% sensitivity, 90% specificity). In the menopausal population, the best predictive performance was obtained by an insulin AUC of 10,000 microIU/ml or more (>/=71,750 pmol/liter) x 240 min (70% sensitivity, 88% specificity). CONCLUSIONS: The presence of high correlation coefficients does not necessarily mean that the indexes of insulin resistance have an optimal predictive performance; this is probably due to the presence of many borderline values. The simple evaluation of insulin AUC seems to effectively replace the euglycemic-hyperinsulinemic clamp in routine clinical practice, allowing results superimposable to those obtained by minimal model analysis.

Adolescent↗

PubMed2004

Stability of adrenocortical steroidogenesis over time in healthy women and women with polycystic ovary syndrome.

Adrenocortical secretion is up-regulated in women with polycystic ovary syndrome (PCOS), and absolute adrenal androgen (AA) excess is evident in approximately 25% of these patients. We hypothesized that AA biosynthesis is an inherited trait and that, as for other inherited traits, AA biosynthesis remains stable over time. To test this hypothesis, we prospectively studied 23 off-treatment PCOS patients and seven age- and body mass index-matched control women on two separate occasions 3-5 yr apart (45.0 +/- 19.0 months and 47.4 +/- 21.3 months, respectively; P > 0.05). All subjects underwent an acute adrenal stimulation using 0.25 mg ACTH-(1-24), and dehydroepiandrosterone (DHEA), androstenedione, and cortisol (F) were measured 0 and 60 min post ACTH; basal levels of total and free testosterone (T), SHBG, and DHEA sulfate (DHEA-S) were also assessed. Among PCOS patients, the mean DHEA-S levels during the repeat study were significantly lower when compared with the initial assessment (170 +/- 107 microg/dl vs. 134 +/- 79 microg/dl, respectively; P = 0.02). However, only patients with initial DHEA-S levels above the median (high DHEA-S) experienced a net decrease in the levels of this metabolite (252.5 +/- 99.2 microg/dl vs. 174.3 +/- 82.5 microg/dl; P = 0.001) over the time of the study; patients with initial DHEA-S levels in the lower half (low DHEA-S) did not experience a change in DHEA-S (94.6 +/- 28.9 microg/dl vs. 97.7 +/- 56.5 microg/dl; P = 0.85). In patients, the total T levels tended to be higher at the second study, although SHBG levels were also higher, resulting in unchanged free T levels over time. Among controls, no significant changes in basal androgens were observed over the time of the study. There were no significant differences in either the basal or ACTH-stimulated levels of DHEA, androstenedione, or F over the time of the study in either PCOS or control women. We conclude that the adrenocortical secretion of AAs or F in PCOS and control women remains stable over time, supporting the hypothesis that the adrenal response to ACTH may be an inherited trait. Alternatively, a decrease in DHEA-S levels over time was observed but only among PCOS patients whose initial levels of this metabolite were above the group median, suggesting that the activity of sulfotransferase in these patients may be up-regulated by factors other than those affecting adrenocortical biosynthesis and that such regulatory influences attenuate over time.

Adrenal Cortex Hormones↗

PubMed2005

Resistin stimulation of 17alpha-hydroxylase activity in ovarian theca cells in vitro: relevance to polycystic ovary syndrome.

CONTEXT: A newly discovered hormone resistin has been shown to be increased in women with polycystic ovary syndrome (PCOS). OBJECTIVE: The purpose of this study was to confirm increased resistin concentrations in women with PCOS and to test the direct effect of resistin on human theca cell androgen production. DESIGN: Resistin was measured in fasting serum samples by RIA. To test the direct effects of resistin on ovarian androgen biosynthesis, human theca cells were cultured with resistin for 3 d in the presence and absence of forskolin and insulin. PATIENTS: Fasting serum samples were obtained from 45 women with PCOS and 74 regularly cycling premenopausal control women in the follicular phase of their menstrual cycles, and ovarian theca cell cultures were established from two control women. RESULTS: The mean serum resistin concentration was increased (40%) in women with PCOS. Serum resistin concentrations correlated positively with body mass index and testosterone in PCOS women but not in controls. There were no significant correlations between resistin and fasting insulin or indicators of insulin resistance when corrected for body mass index. In cultured human theca cells, basal 17alpha-hydroxylase activity was unchanged by resistin alone, but resistin enhanced 17alpha-hydroxylase activity in the presence of forskolin or a combination of forskolin plus insulin. Resistin (> or =1 ng/ml) augmented forskolin and forskolin plus insulin stimulation of CYP17 mRNA expression in a concentration-dependent manner. CONCLUSION: These data indicate that abnormal resistin secretion in PCOS may play a role in causing ovarian hyperandrogenism.

Adult↗

PubMed2005

Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span.

CONTEXT: The polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of reproductive-aged women today, affecting approximately 6.6% of unselected reproductive-aged women (approximately 4 million women in the United States) (1990 National Institutes of Health criteria), and potentially represents a significant financial burden to our health care. OBJECTIVE: The objective of the study was to define, using current definitions and prevalence or incidence data, the minimal economic burden that PCOS in reproductive-aged women represents for the United States. DESIGN: The study design was a literature review. SETTING: The study was conducted at a tertiary care center. PATIENTS OR OTHER PARTICIPANTS: There were no patients or other participants. INTERVENTION(S): We performed a systematic review of the published medical literature to identify studies evaluating epidemiology of reproductive-age PCOS and its clinical consequences and costs. We tied general societal cost data for the different health consequences to reproductive-age PCOS costs, using prevalence data. MAIN OUTCOME MEASURE(S): The main measure in the study was total health care-related economic costs. RESULTS: We estimated the mean annual cost of the initial evaluation to be dollar 93 million (2.1% of total costs), that of hormonally treating menstrual dysfunction/abnormal uterine bleeding to be dollar 1.35 billion (31.0% of total), that of providing infertility care to be dollar 533 million (12.2% of total), that of PCOS-associated diabetes to be dollar 1.77 billion (40.5% of total), and that of treating hirsutism to be dollar 622 million (14.2% of total). CONCLUSIONS: The total cost of evaluating and providing care to reproductive-aged PCOS women in the United States is dollar 4.36 billion. Because the cost of the diagnostic evaluation accounted for a relatively minor part of the total costs (approximately 2%), more widespread and liberal screening for the disorder appears be a cost-effective strategy, leading to earlier diagnosis and intervention and possibly the amelioration and prevention of serious sequelae.

Adolescent↗

PubMed2005

Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) and the metabolic syndrome have many features in common and may share the same pathogenesis. OBJECTIVE: This study was performed to determine the prevalence and predictors of the metabolic syndrome in PCOS. DESIGN: The clinical, hormonal, and oral glucose tolerance test results were analyzed in 394 PCOS women who were screened for participation in a multicenter trial to evaluate the effects of troglitazone on ovulation and hirsutism. SETTING: A multicenter clinical trial is presented. PATIENTS OR OTHER PARTICIPANTS: The subjects were women with PCOS who had or lacked the metabolic syndrome. MAIN OUTCOME MEASURES: Waist circumference, fasting glucose, high-density lipoprotein cholesterol and triglyceride concentrations, and blood pressure were the main outcome measures. RESULTS: Twenty-six (6.6%) subjects had diabetes; among the 368 nondiabetics, the prevalence for individual components comprising the metabolic syndrome were: waist circumference greater than 88 cm in 80%, high-density lipoprotein cholesterol less than 50 mg/dl in 66%, triglycerides greater than or equal to 150 mg/dl in 32%, blood pressure greater than or equal to 130/85 mm Hg in 21%, and fasting glucose concentrations greater than or equal to 110 mg/dl in 5%. Three or more of these individual criteria were present in 123 (33.4%) subjects overall. The prevalence of the metabolic syndrome did not differ significantly between racial/ethnic groups. The prevalence of the metabolic syndrome from lowest to highest quartile of free testosterone concentration was 19.8, 31.3, 46.9, and 35.0%, respectively [P = 0.056 adjusted for body mass index (BMI)]. None of the 52 women with a BMI less than 27.0 kg/m2 had the metabolic syndrome; those in the top BMI quartile were 13.7 times more likely (95% confidence interval, 5.7-33.0) to have the metabolic syndrome compared with those in the lowest quartile. Thirty-eight percent of those with the metabolic syndrome had impaired glucose tolerance compared with 19% without the metabolic syndrome (P < 0.001). CONCLUSIONS: The metabolic syndrome and its individual components are common in PCOS, particularly among women with the highest insulin levels and BMI. Hyperinsulinemia is a likely common pathogenetic factor for both PCOS and the metabolic syndrome.

Adult↗

PubMed2005

The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery.

CONTEXT: The polycystic ovary syndrome (PCOS) is frequently associated with obesity. However, there are very few data about PCOS in morbid obesity, especially with regard to its evolution after bariatric surgery. OBJECTIVE: The objective of this study was to evaluate the response of PCOS to the sustained and marked weight loss achieved by bariatric surgery in morbidly obese women. DESIGN: This was a longitudinal prospective nonrandomized evaluation. SETTINGS: The study was performed at an academic hospital. PATIENTS: Thirty-six consecutive premenopausal women submitted to bariatric surgery were screened for PCOS, which was present in 17. INTERVENTIONS: Bariatric surgery was performed. MAIN OUTCOME MEASURES: Hyperandrogenism, menstrual function, and insulin resistance were estimated before and at least 6 months after bariatric surgery in 12 patients with PCOS. RESULTS: Weight loss (41 +/- 9 kg after 12 +/- 5 months) was paralleled by decreases in the hirsutism score (from 9.5 +/- 6.8 to 4.9 +/- 4.2; P = 0.001), total (69 +/- 32 to 42 +/- 19 ng/dl; P < 0.02) and free testosterone (from 1.6 +/- 0.7 to 0.6 +/- 0.3 ng/dl; P < 0.005), androstenedione (from 4.1 +/- 1.5 to 3.0 +/- 0.9 ng/ml; P < 0.02), and dehydroepiandrosterone sulfate (from 2000 +/- 1125 to 1353 +/- 759 ng/ml; P < 0.005); amelioration of insulin resistance estimated by homeostasis model assessment (from 6.0 +/- 3.0 to 1.6 +/- 1.0; P < 0.001); and restoration of regular menstrual cycles and/or ovulation in all patients. CONCLUSIONS: The PCOS is a frequent finding in women with morbid obesity and may resolve after weight loss induced by bariatric surgery.

Adult↗

PubMed2005

Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome.

CONTEXT: Despite its frequency, the polycystic ovary syndrome (PCOS) is still a difficult diagnosis in endocrinology, gynecology, and reproductive medicine. To help solve this issue, the Rotterdam consensus conference proposed to include the ultrasonographic follicle count as a new diagnostic criterion, in addition to hyperandrogenism and oligo-anovulation. Unfortunately, its assessment does not offer sufficient reliability worldwide. OBJECTIVE: The aim of our study was to check whether anti-Müllerian hormone (AMH) measurement in the serum could be a surrogate for antral follicle count in the diagnostic criteria of PCOS. DESIGN, SETTING, AND PATIENTS: Serum AMH was measured with a second-generation immunoassay in a cohort of 73 PCOS patients and 96 controls, and its diagnostic power was evaluated by receiver operating characteristic curves. PCOS was diagnosed according to the Rotterdam definition. RESULTS: Serum AMH levels were 3-fold higher in PCOS patients than in controls (81.6 vs. 33.5 pmol/liter; P < 0.001) and were significantly related to the follicle number in the two groups. The area under the receiver operating characteristic curve for the AMH assay was 0.851, indicating a good diagnostic potency. Setting the threshold at 60 pmol/liter offered the best compromise between specificity (92%) and sensitivity (67%). CONCLUSIONS: The serum AMH level is an accurate marker of the ovarian early antral follicle number and offers a good diagnostic potency. In situations where accurate ultrasonographic data are not available, AMH could thus be used instead of the follicle count as a diagnostic criterion and incorporated as such in the Rotterdam definition of PCOS.

Adolescent↗

PubMed1993

Normal basal and insulin-stimulated fuel metabolism in lean women with the polycystic ovary syndrome.

Many reports have suggested that hyperandrogenaemic patients with the polycystic ovary syndrome (PCOS) may be insulin resistant. However, there have also been suggestions that their insulin resistance may relate to obesity and android fat distribution. To assess whether PCOS induces metabolic disturbances independently of obesity, we studied seven lean patients with PCOS (age, 27.1 +/- 2.0 yr; body mass index, 22.2 +/- 0.78 kg/m2; waist/hip ratio, 0.79 +/- 0.02; fat-free mass, 46.38 +/- 1.13 kg) and seven normal women (age, 25.7 +/- 1.4 yr; body mass index, 21.3 +/- 0.69 kg/m2; waist/hip ratio, 0.74 +/- 0.02; fat-free mass, 50.1 +/- 1.51 kg) for 3 h in the basal period and 2 h during a hyperinsulinemic (0.4 mU/kg.min) euglycemic clamp. In the basal state, comparable metabolic indices were recorded: serum insulin, 35.9 +/- 7.7 (PCOS) vs. 37.3 +/- 2.87 pmol/L (controls); plasma C-peptide, 364.1 +/- 66.2 vs. 397.2 +/- 66.2 pmol/L; plasma glucose, 4.95 +/- 0.09 vs. 4.77 +/- 0.09 mmol/L; forearm arterio-venous difference in glucose, 0.17 +/- 0.04 vs. 0.15 +/- 0.07 mmol/L; isotopically determined endogenous glucose production, 1.9 +/- 0.1 vs. 2.0 +/- 0.1 mg/kg.min; and serum nonesterified fatty acids, 545 +/- 40 vs. 617 +/- 54 mumol/L (all P > 0.05). During the clamp, all recordings were again similar: serum insulin, 282.7 +/- 21.5 vs. 270.5 +/- 13.6 pmol/L; plasma C-peptide, 331.0 +/- 33.1 vs. 364.1 +/- 66.2 pmol/L; plasma glucose, 4.99 +/- 0.07 vs. 4.99 +/- 0.05 mmol/L; glucose arterio-venous difference, 1.01 +/- 0.18 vs. 0.85 +/- 0.12 mmol/L; endogenous glucose production, -0.9 +/- 0.1 vs. -0.5 +/- 0.2 mg/kg.min; amount of exogenous glucose necessary to maintain euglycemia, 4.0 +/- 0.4 vs. 3.8 +/- 0.5 mg/kg.min; and nonesterified fatty acids, 205 +/- 7 vs. 246 +/- 18 mumol/L (all P > 0.05). By showing normal basal and insulin-stimulated substrate metabolism in lean hyperandrogenemic PCOS patients, these data suggest that insulin resistance may be an epiphenomenon, rather than a primary feature of PCOS.

Adult↗

PubMed1994

Expression of the genes encoding the insulin-like growth factors (IGF-I and II), the IGF and insulin receptors, and IGF-binding proteins-1-6 and the localization of their gene products in normal and polycystic ovary syndrome ovaries.

To discern the potential role of the insulin-like growth factors (IGFs) in polycystic ovary syndrome (PCOS), we examined the expression of the genes encoding the IGFs, IGF receptors (IGFr), insulin receptor (Ir), and IGF-binding proteins (IGFBPs-1-6) as well as the localization of the gene products in specific cellular compartments of normal and PCOS human ovaries. Messenger ribonucleic acid (mRNA) was localized by in situ hybridization with specific 35S-labeled human antisense RNA probes, and protein was detected by immunohistochemistry using specific antisera. Thecal cells, but not granulosa cells (GC), of small antral follicles (3-6 mm) from PCOS ovaries expressed both IGF-I and IGF-II transcripts. Abundant IGF-Ir mRNA was found only in GC, IGF-IIr mRNA was found in both granulosa and thecal cells, and Ir mRNA was detected in all cell types, including granulosa, thecal, and stromal cells. Localization of the gene products revealed no IGF-I immunoreactivity; however, immunostaining for each of the other gene products was colocalized with its corresponding mRNA. The cellular distribution of mRNA and protein in PCOS follicles was indistinguishable from that observed in small antral follicles from normal ovaries. In dominant follicles, however, IGF-I mRNA was no longer detectable, but abundant IGF-II mRNA was expressed exclusively in GC. Although IGF-Ir mRNA was expressed in GC, IGF-IIr mRNA was found in both granulosa and thecal cells. In follicles taken from PCOS ovaries, no IGFBP-1 mRNA was detected, IGFBP-2 mRNA was abundant in both granulosa and thecal cells, moderate IGFBP-3 mRNA was found only in thecal cells, IGFBP-4 and -5 mRNAs were present in all cellular compartments, and IGFBP-6 mRNA was not detected. Localization of the gene products by immunostaining revealed that each protein colocalized with its corresponding mRNA. The cellular distribution of IGFBP mRNA and protein in PCOS follicles was also indistinguishable from that in small antral follicles of normal ovaries, but remarkable differences were found in dominant follicles, where abundant IGFBP-1 mRNA was seen exclusively in GC, IGFBP-2 mRNA in thecal cells, and IGFBP-3 mRNA in both granulosa and thecal cells. Moderate expression of the IGFBP-4 and IGFBP-5 genes was seen in all cell types, including stromal cells, but no IGFBP-6 mRNA was detected. Again, each of the gene products colocalized with its corresponding mRNA. We conclude the following.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1996

The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome.

We performed this study to investigate the hypothesis that insulin resistance plays a role in the pathogenesis of reproductive abnormalities in women with the polycystic ovary syndrome (PCOS). Twenty-five women with PCOS were enrolled in a double-blind randomized 3-month trial of two doses of the insulin-sensitizing agent, troglitazone, 21 of whom completed the study: 200 mg, n = 10; 400 mg, n = 11. Baseline hormonal parameters and glucose tolerance were compared with 12 age- and weight-matched ovulatory control women. There were no significant changes in body mass index during the study. Fasting (P < 0.01) and 2-h post-75-g glucose load insulin levels (P < 0.05), as well as integrated insulin responses to the glucose load, decreased (P < 0.05), and insulin sensitivity assessed by a frequently sampled iv glucose tolerance test increased significantly (P < 0.001) during troglitazone treatment. This was accompanied by significant decreases in the levels of nonsex hormone-binding globulin-bound testosterone (P < 0.01), dehydroepiandrosterone sulfate (P < 0.001), estradiol (P < 0.01), and estrone (P < 0.001). Stepwise regression analysis indicated that decreases in nonsex hormone-binding globulin testosterone levels were significantly correlated with decreases in integrated insulin responses to the glucose load (r2 0.44, P < 0.01). The only significant changes at the 200-mg troglitazone dose were an increase in insulin sensitivity (P < 0.05) and decreases in dehydro-epiandrosterone sulfate (P < 0.01) and estrone (P < 0.05) levels. At the 400-mg dose, in addition to the changes noted in the entire troglitazone treatment group, increases in the disposition index (the product of insulin sensitivity and secretion) achieved significance, as did decreases in androstenedione (P < 0.01) and LH (P < 0.05) levels and increases in sex hormone-binding globulin levels (P < 0.01). Two PCOS women had ovulatory menses. We conclude that 1) troglitazone improves total body insulin action in PCOS, resulting in lower circulating insulin levels; 2) insulin resistance, probably via hyperinsulinemia, results in a general augmentation of steroidogenesis and LH release in PCOS; and 3) insulin-sensitizing agents, such as troglitazone, may provide a novel therapy for PCOS.

Adult↗

PubMed1997

Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance?

The polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is characterized by metabolic and cardiovascular aberrations similar to those seen in the so-called insulin resistance syndrome. The regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 10 nonobese women with PCOS and in 11 age- and body mass index-matched healthy women. Eight PCOS women were reinvestigated after 3 months of treatment with combined oral contraceptives containing ethinyl estradiol and norethisterone, which normalized hyperandrogenicity. The PCOS women showed a marked resistance to the lipolytic effect of noradrenaline due to defects at two different levels in the lipolytic cascade: first, a 7-fold reduction in sensitivity to the beta 2-selective agonist terbutaline (P < 0.005), which could be ascribed to a 50% lower beta 2-adrenoceptor density (P < 0.02) as determined with radioligand binding; there was no difference with regard to dobutamine (beta 1) or clonidine (alpha 2-sensitivity) or beta 1-adrenoceptor density; second, the maximum lipolytic response was also 35% lower (P < 0.02) in the PCOS women compared to that in the healthy women. This was seen with all beta-adrenergic agonists and the postreceptor-acting agents forskolin (activating adenylyl cyclase) and dibutyryl cAMP (activating protein kinase). Neither beta 2-adrenoceptor sensitivity or density nor the reduced lipolytic responsiveness was restored by 3 months of oral contraceptives treatment. The results indicate the existence of a marked impairment of catecholamine-induced lipolysis in nonobese PCOS women displaying early features of the insulin resistance syndrome due to multiple lipolysis defects as a lower beta 2-adrenoceptor density and reduced function of the protein kinase, hormone-sensitive lipase complex. These lipolysis defects are identical to those observed in the insulin resistance (metabolic) syndrome and could be a primary pathogenic mechanism for the development of these disorders.

Adipocytes↗