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[Features of morphometry of ultrasound and endometrial histology in the anovulatory polycystic ovary syndrome women].

OBJECTIVE: To investigate the relationship between ultrasonographic features of endometrium and the relation of histological staging of the endometrium and sexual hormone levels in anovulatory polycystic ovary syndrome (PCOS) women. METHODS: Seventy-six anovulatory PCOS patients and 32 women with normal ovulation were enrolled in this study. Ultrasonographic examination, and transmission electron microscope were used to observe endometrium. The expressions of nulear antigen associated with cell proliferation Ki-67 and calcitonin were analyzed by immunohistochemistry. The sexual hormone levels were measured by chemiluminescent microparticle immunoassay. RESULTS: In 11 patients the endometrium showed secretory change out of 76 anovulatory PCOS patients. The frequency of secretory change of the endometrium was not increased with the increase of menses-biopsy interval (P > 0.05). The frequency of abnormal stroma was significantly lower in tripleline endometria than those in non-tripleline endometria (9% vs 43%, P < 0.05). Compared with the control group, the anovulatory PCOS group showed a significant higher expression of Ki-67 in the glandular cell of the secretory phase endometrium (P < 0.05). In the proliferative endometrium, anovulatory PCOS group had more cell organelles than those of the control group. The endometrium showed insufficient secretory changes in the anovulatory PCOS patients. CONCLUSIONS: Proliferative and secretory stage of the endometrium in the anovulatory PCOS group show abnormal features. The abnormal stroma may contribute to the hyperechonic images of the endometrium in the anovulatory PCOS patients.

Adult↗

Serum total renin is elevated in women with polycystic ovarian syndrome.

OBJECTIVE: To examine the serum total renin in women with polycystic ovarian syndrome (PCOS) and in controls. SETTING: Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS: Forty-four oligomenorrheic women with PCOS (body mass index [BMI] 18.0 to 49.0 kg/m2) and 25 control women with regular menstrual cycles (BMI 18.0 to 53.5 kg/m2). MAIN OUTCOME MEASURES: The concentrations of total renin, LH, FSH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and insulin in serum. RESULTS: The concentration of total renin in serum was higher in PCOS women than in healthy women independently of BMI, age, or serum insulin. The serum total renin measurement discriminated PCOS patients and control women to a similar extent as the previously used hormonal parameters (LH:FSH, T, A, and T:SHBG) as judged by receiver-operating characteristic analysis. Positive correlations were found between the serum total renin level and LH concentration, LH:FSH ratio, T and A levels, and T:SHBG ratio. Analysis of serum total renin in PCOS patients during oligomenorrhea and after menstruation did not reveal any significant changes. CONCLUSIONS: The elevated concentration of serum total renin suggests an enhanced activity of ovarian renin-angiotensin system in PCOS. The determination of serum total renin may provide a novel tool in the diagnostics of PCOS, because its serum level is elevated in PCOS women independently of BMI and serum insulin.

Adult↗

Polycystic Ovary Syndrome Physiologic Pathways Implicated Through Clustering of Genetic Loci.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, with disease loci identified from genome-wide association studies (GWAS) having largely unknown relationships to disease pathogenesis. OBJECTIVE: This work aimed to group PCOS GWAS loci into genetic clusters associated with disease pathophysiology. METHODS: Cluster analysis was performed for 60 PCOS-associated genetic variants and 49 traits using GWAS summary statistics. Cluster-specific PCOS partitioned polygenic scores (pPS) were generated and tested for association with clinical phenotypes in the Mass General Brigham Biobank (MGBB, N = 62 252). Associations with clinical outcomes (type 2 diabetes [T2D], coronary artery disease [CAD], and female reproductive traits) were assessed using both GWAS-based pPS (DIAMANTE, N = 898,130, CARDIOGRAM/UKBB, N = 547 261) and individual-level pPS in MGBB. RESULTS: Four PCOS genetic clusters were identified with top loci indicated as following: (i) cluster 1/obesity/insulin resistance (FTO); (ii) cluster 2/hormonal/menstrual cycle changes (FSHB); (iii) cluster 3/blood markers/inflammation (ATXN2/SH2B3); (iv) cluster 4/metabolic changes (MAF, SLC38A11). Cluster pPS were associated with distinct clinical traits: Cluster 1 with increased body mass index (P = 6.6 &#xd7; 10-29); cluster 2 with increased age of menarche (P = 1.5 &#xd7; 10-4); cluster 3 with multiple decreased blood markers, including mean platelet volume (P = 3.1 &#xd7;10-5); and cluster 4 with increased alkaline phosphatase (P = .007). PCOS genetic clusters GWAS-pPSs were also associated with disease outcomes: cluster 1 pPS with increased T2D (odds ratio [OR] 1.07; P = 7.3 &#xd7; 10-50), with replication in MGBB all participants (OR 1.09, P = 2.7 &#xd7; 10-7) and females only (OR 1.11, 4.8 &#xd7; 10-5). CONCLUSION: Distinct genetic backgrounds in individuals with PCOS may underlie clinical heterogeneity and disease outcomes.

Humans↗

Gonadotrophin therapy for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: Approximately 15% of patients with PCOS remain anovulatory despite treatment with oral anti-oestrogen medications such as clomiphene citrate. In addition, about half of women with PCOS ovulating on anti-oestrogen treatment fail to conceive. Gonadotrophin stimulation is the next step in treatment for women who are "clomiphene resistant", however, results of gonadotrophin stimulation in women with PCOS are less successful. In PCOS associated with hypersecretion of LH, purified urinary follicle-stimulating hormone (u-FSH) preparations have theoretical advantages over the use of human menopausal gonadotrophin (hMG) preparations (containing both FSH and LH), but whether this claimed advantage extends into clinical practice remains uncertain. In addition, the use of gonadotrophin-releasing hormone analogues (GnRH-a) to produce pituitary desensitisation prior to ovulation induction in PCOS has been claimed to increase the success rates of treatment as well as reduce complications such as OHSS and multiple pregnancy. Gonadotrophin preparations have also been administered via different routes (intramuscular or subcutaneous), or using different stimulation regimens and protocols (step-up or standard) in an attempt to improve efficacy. OBJECTIVES: To determine the effectiveness of urinary-derived gonadotrophins as ovulation induction agents in patients with PCOS trying to conceive. In particular, to assess the effectiveness of (1) different gonadotrophin preparations, (2) the addition of a gonadotrophin-releasing hormone agonist (GnRH-a) to gonadotrophin stimulation and (3) different modalities of gonadotrophin administration. SEARCH STRATEGY: The search strategy to identify RCTs consisted of (1) the Group's Specialised Register of Controlled Trials using the search strategy developed for the Menstrual Disorders and Subfertility Group as a whole (see the Review Group details for more information), (2) additional specific electronic Medline searches and (3) bibliographies of identified studies and narrative reviews. SELECTION CRITERIA: RCTs in which urinary-derived gonadotrophins were used for ovulation induction in patients with primary or secondary subfertility attributable to PCOS. DATA COLLECTION AND ANALYSIS: Twenty three RCTs were identified, 9 of which were excluded from analysis. The data were extracted independently by 2 authors. The following criteria were assessed: (1) the methodological characteristics of the trials, (2) the baseline characteristics of the studied groups and (3) the outcomes of interest: pregnancy rate (per cycle), ovulation rate (per cycle), miscarriage rate (per pregnancy), multiple pregnancy rate (per pregnancy), overstimulation rate (per cycle) and ovarian hyperstimulation syndrome (OHSS) rate (per cycle). Where suitable, meta-analysis was performed using Peto's OR with 95% CI with the fixed effect Mantel-Haentszel equation. MAIN RESULTS: (1) A reduction in the incidence of OHSS with FSH compared to hMG in stimulation cycles without the concomitant use of a GnRH-a (OR 0.20; 95% CI 0.08-0.46) and (2) a higher overstimulation rate when a GnRH-a is added to gonadotrophins (OR 3.15; 95% CI 1.48-6.70). REVIEWER'S CONCLUSIONS: Although 14 RCTs were included in this review, few dealt with the same comparisons, all were small to moderate size and their methodological quality was generally poor. Any conclusions, therefore, remain tentative as they are based on a limited amount of data and will require further RCTs to substantiate them. In none of the comparisons was there a significant improvement in pregnancy rate but this may be due to the lack of power (i.e. insufficient patients randomised to demonstrate a significant difference between treatments). There was a trend towards better pregnancy rates with the addition of a GnRH-a to gonadotrophin stimulation and these interventions warrant further study. Despite theoretical advantages, urinary-derived FSH preparations did not improve pregnancy rates when compared to traditional and cheaper hMG preparations; their only demonstrable benefit was a reduced risk of OHSS in cycles when administered without the concomitant use of a GnRH-a. No conclusions can be drawn on miscarriage and multiple pregnancy rates due to insufficient reporting of these outcomes in the trials.

Female↗

Growth-hormone response to combined stimulation with GHRH plus GH-releasing peptide-6 in obese patients with polycystic ovary syndrome before and after short-term fasting.

Controversial data were reported on GH response to different provocative stimuli in obese patients with polycystic ovary syndrome (PCOS). The objective of our study was to assess the effect of short-term fasting on GH response to combined stimulus with GHRH+GH-releasing peptide-6 (GHRP-6) in obese patients with PCOS and possible relation with leptin and insulin changes during fasting. Twelve obese PCOS women and nine obese control women participated in 3-day fasting. GH response, IGF-I, insulin and leptin were measured after GHRH+ GHRP-6, before and after short-term fasting. Obese PCOS patients had significantly greater GH peak after GHRH+GHRP-6 before fasting. Enhanced response to GH stimulation was found after fasting without substantial differences between obese PCOS and obese controls. Insulin and leptin significantly decreased, while insulin sensitivity significantly improved in both groups during fasting. In conclusion, obese PCOS patients have peculiar type of GH response to GHRH+GHRP-6 before fasting, possibly due to enhanced sensitivity of somatotrophs. Observed changes in insulin and leptin may participate in modulation of enhanced GH response after short-term fasting to GHRH+GHRP-6 in PCOS and obese controls.

Adult↗

Body composition, fat distribution and metabolic characteristics in lean and obese women with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS), characterized by chronic anovulation and hyperandrogenism, has many features of metabolic syndrome and can be considered a metabolic disease. Approximately 50% of patients with PCOS are overweight or obese with abdominal fat accumulation. Some metabolic alterations and abdominal fat distribution have also been reported in lean women with PCOS. The aim of this study was to evaluate the effect, if any, of obesity on metabolic features, body composition and fat distribution in patients with PCOS. Body composition and abdominal fat distribution (evaluated by DEXA), waist circumference, blood pressure, lipid profile, glucose tolerance and homeostasis model assessment index were determined in 23 lean [mean age 23 +/- 5 yr, mean body mass index (BMI) 22 +/- 2 kg/m2] and 27 overweight-obese (mean age 21 +/- 5 yr, mean BMI 32 +/- 5 kg/m2) patients with PCOS and in 20 age- and weight-matched eumenorrhoic women. Patients exhibited slight but non-significant differences in metabolic parameters, waist circumference, blood pressure and total and abdominal fat content compared with weight-matched controls. None of the lean subjects suffered from metabolic syndrome according to the National Cholesterol Education Program--Adult Treatment Panel III (NCEP-ATPIII) criteria as opposed to 10 overweight-obese patients and three overweight-obese control subjects (37% and 33.3% of each subgroup, respectively). Our data do not show significant metabolic alterations in lean PCOS women. Results indicate that obesity seems to underpin the metabolic alterations exhibited by the overweight-obese patients. However, since women with PCOS are at increased cardiovascular risk, further studies are needed to evaluate metabolic alterations and body composition in these patients.

Adipose Tissue↗

Upregulation of adiponectin receptor 1 and 2 mRNA and protein in adipose tissue and adipocytes in insulin-resistant women with polycystic ovary syndrome.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistance (IR) and obesity. Adiponectin, which is lower in IR states, exerts its glucose-lowering and anti-inflammatory effects by activating two receptors, ADIPOR1 and ADIPOR2. There are no data on the relative expression of these receptors in adipose tissue of PCOS women. METHODS: We investigated the expression of adiponectin receptors from corresponding s.c. and omental (o.m.) adipose tissue in women with PCOS compared with matched non-PCOS women. As there is a disturbance in the steroid milieu in PCOS women, we also assessed the effects of testosterone and oestradiol on adiponectin receptors using adipocytes and adipocyte explants. Real-time RT-PCR and western blotting were used to assess the relative adiponectin receptor mRNA expression and protein production, respectively. Biochemical measurements were performed in our hospital's laboratory. RESULTS: We are the first to describe adiponectin receptor expression and production, in corresponding s.c. and o.m. human adipose tissues at the mRNA and protein level. We demonstrate the upregulation of mRNA expression and protein production of adiponectin receptors in women with PCOS, in s.c. and o.m. adipose tissue. Treatment of adipose tissue explants and adipocytes with testosterone and oestradiol induced the expression of adiponectin receptor mRNA and protein. There was a significant positive association between ADIPOR1/R2 expression and homeostasis model assessment, testosterone, oestradiol and triglycerides and a negative relationship with sex hormone-binding globulin. CONCLUSIONS/INTERPRETATION: The precise reason for the upregulation of adiponectin receptors seen in PCOS women, a pro-diabetic state, is unknown, but it appears that sex steroids may play a role in their regulation in adipose tissue.

Adipocytes↗

Relationship between bone mineral density and insulin resistance in polycystic ovary syndrome.

The aim of the present study was to evaluate whether there is a relationship between bone mineral density (BMD) and insulin resistance and hyperinsulinemia in women with polycystic ovary syndrome (PCOS). The study consisted of 28 amenorrheic women with PCOS and 11 amenorrheic women without PCOS. Fifteen healthy women with normal ovulatory function, matched for age and body mass index (BMI), served as controls. BMD was measured at the lumbar spine and left femoral neck with dual-energy X-ray absorptiometry. Blood samples were obtained to measure serum levels of insulin, follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin (SHBG), total and free testosterone, androstenedione and estradiol by radioimmunassay. Insulin resistance was estimated by the in sulin tolerance test (ITT), and K(ITT) was taken as the insulin sensitivity index. In the PCOS group, K(ITT) was significantly lower and insulin levels were higher than in either of the control groups (P < 0.001). BMD in the PCOS group was lower than in the healthy group and higher than in the amenorrheic control group (P < 0.05). In the PCOS group, there were positive correlations of BMD of the lumbar spine with insulin (r = 0.42: P < 0.05) and negative correlations of BMD with K(ITT) (r = -0.58; P < 0.001) and SHBG (r = -0.38; P < 0.05). The inverse association of BMD and K(ITT) was independent of BMI, insulin, SHBG, androstenedione, and free testosterone. In conclusion, insulin resistance and hyperinsulinemia in women with PCOS may be a relative protective factor against bone mineral loss.

Adolescent↗

Severe impairment of insulin action in adipocytes from amenorrheic subjects with polycystic ovary syndrome.

Adipose tissue was used to characterize the metabolic abnormality of insulin resistance in polycystic ovary syndrome (PCOS). Nine patients with PCOS were studied during a period of amenorrhea and confirmed to be chronically anovulatory by vaginal ultrasound and plasma progesterone measurements. These were compared with six age- and body mass index (BMI)-matched controls (BMI, 27.2 +/- 2.2 in PCOS and 24.7 +/- 2.3 in control subjects). Insulin receptor binding was measured and insulin action was assessed by measuring initial rates of 3-O-methylglucose uptake and by inhibition of lipolysis. The maximum specific insulin receptor binding was 0.62% +/- 0.12% and 1.78% +/- 0.18% per 10-cm2 cell surface (mean +/- SEM) in PCOS and control subjects, respectively (P < .001). Maximum rates of glucose transport were also impaired as compared with controls, with 3-O-methylglucose transport being 0.90 +/- 0.15 versus 1.57 +/- 0.28 pmol/10 cm2/5 s, respectively (P < .05). The concentration of insulin required for half-maximal stimulation of glucose uptake was 165 +/- 36 versus 32 +/- 10 pmol in PCOS and control subjects, respectively (P < .05). The maximum percentage lipolysis inhibition (mean +/- SEM) was 9.5% +/- 1.6% in PCOS and 28.3% +/- 7.2% in control patients, respectively (P < .01). These data demonstrate that there are both insulin binding and postreceptor defects in adipocytes from amenorrheic PCOS subjects. The degree of defect in adipocyte insulin action is greater than would have been anticipated from in vivo data.

Adipocytes↗

Circulating and ovarian IGF binding proteins: potential roles in normo-ovulatory cycles and in polycystic ovarian syndrome.

IGFs function as co-gonadotropins in the ovary, facilitating steroidogenesis and follicle growth. IGFBP-1 to -5 are expressed in human ovary and mostly inhibit IGF action in in vitro ovarian cell culture systems. In the clinical disorder of polycystic ovarian syndrome (PCOS), which is characterized by hyperandrogenemia, polycystic ovaries and anovulation, follicles have a higher androgen: estradiol (A : E2) content and growth is arrested at the small antral stage. In the PCOS follicle, follicle stimulating hormone (FSH) and IGF levels are in the physiologic range, and even in the face of abundant androstenedione (AD) substrate, aromatase activity and E2 production are low. When PCOS granulosa are removed from their ovarian environment, they respond normally or hyperrespond to FSH. It has been postulated that an inhibitor of IGF's synergistic actions with FSH on aromatase activity may be one (or more) of the IGFBPs, which contributes to the arrested state of follicular development commonly observed in this disorder. High levels of IGFBP-2 and IGFBP-4 are present in follicular fluid (FF) from androgen-dominant follicles (FFa) from normally cycling women and in women with PCOS. This is in marked contrast to the near absence of these IGFBPs in estrogen-dominant FF (FFe), determined by Western ligand blotting. Regulation of granulosa-derived IGFBPs is effected by gonadotropins and insulin-like peptides. In addition, an IGFBP-4 metallo-serine protease is present in FFe, but not in FFa in ovaries from normally cycling women and those with PCOS, although the IGFBP-4 protease is present in PCOS follicles hyperstimulated for in vitro fertilization. Recent studies demonstrate that IGF-II in FFe is higher than in FFa' whereas IGF-I, IGFBP-3 and IGFBP-1 levels do not differ, underscoring the importance of local IGF-II production by the granulosa and the importance of IGFBP-4 and IGFBP-2 in regulation of IGF-II action within the follicle during its developmental pathway as an E2- or A-dominant follicle. In the androgen-treated female-to-male transsexual (TSX) model for PCOS, IGF-I, IGF-II, IGFBP-3 and IGFBP-1 levels do not differ.

Female↗

Genomic variants in polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women, characterized by the presence, among other traits, of hyperandrogenism, insulin resistance, and hyperinsulinism. The familial aggregation of PCOS lead the interest to the molecular genetic basis of this syndrome, especially to the genes encoding proteins involved in androgen synthesis and the regulation of insulin synthesis and action. Considering the relationship between insulin resistance and chronic inflammation, and the clustering of inflammatory markers in PCOS patients, recent studies focused on the involvement of proinflammatory genotypes on the pathogenesis of PCOS. Mounting evidence suggest at present a complex model of inheritance for PCOS, in which predisposing and protecting genomic variants interact with environmental factors such as obesity and a sedentary lifestyle, finally leading to the classic phenotype of this syndrome. Moreover, the association of hyperandrogenism, insulin resistance and chronic inflammation raised the possibility of an increase risk of cardiovascular disease in women suffering from PCOS. In the present review we will summarize the most important findings published to date regarding the molecular genetic mechanisms underlying the association of PCOS with insulin resistance and chronic inflammation, and the possible interaction of these mechanisms with environmental factors.

Female↗

Obesity and extreme obesity, manifest by ages 20-24 years, continuing through 32-41 years in women, should alert physicians to the diagnostic likelihood of polycystic ovary syndrome as a reversible underlying endocrinopathy.

OBJECTIVES: Document obesity-extreme obesity in most 20-24, 25-29, and 32-41 years old women with PCOS as a stimulus for physicians to consider the diagnosis of PCOS, an underlying reversible endocrinopathy. STUDY DESIGN: In matched age groups 20-24, 25-29, and 32-41 years, we compared BMI in 84, 129, and 188 Caucasian women with PCOS versus 956, 815, and 815 women in NHANES I (general population), and 25, 36, and 45 non-pregnant women (community obstetrics practice). RESULTS: At ages 20-24, 25-29, and 32-41 years, mean+/-S.D. BMIs in women with PCOS (35.3+/-7.7, 36.0+/-9.4, 36.7+/-8.2) were much greater than NHANES I (22.8+/-4.6, 23.3+/-5.0, 24.5+/-5.6; p < .0001), and community (26.1+/-6.8, 26.9+/-6.6, 25.2+/-5.2; p < .0001). Classifying BMI <25 (normal), > or =25-30 (overweight), > or =30-40 (obese), > or =40 (extremely obese), at ages 20-24, 25-29, and 32-41 years: 76, 73, and 78% of PCOS women were obese-extremely obese, versus 7, 11, and 14% of NHANES I, and 20, 28, and 15% of community women. At ages 20-24, 25-29, and 32-41 years, only 10, 12, and 7% PCOS women had BMIs <25, versus 78, 74, and 66% NHANES I, and 48, 47, and 58% of community women. CONCLUSIONS: Obesity-extreme obesity in women, manifest by ages 20-24 years, continuing through 32-41 years, should alert physicians to the likelihood of PCOS, an underlying, heritable, potentially reversible, insulin resistant endocrinopathy that promotes obesity.

Adult↗

Adrenocortical hyperresponsiveness to corticotropin in polycystic ovary syndrome patients with adrenal androgen excess.

OBJECTIVE: To test the hypothesis that adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) is due to a generalized exaggeration in AA output in response to adrenocorticotropic hormone (ACTH), and that this abnormality is due to an identifiable alteration in the biosynthesis of AAs. DESIGN: Cross-sectional prospective controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Patients with PCOS (n = 9) and without (n = 9) AA excess and controls (n = 12) without hyperandrogenism, matched for age and body mass. INTERVENTION(S): Acute 60-minute ACTH test was performed on patients. MAIN OUTCOME MEASURE(S): Basal levels of dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, and basal (Steroid(0)) and the 60-minute ACTH-stimulated levels (Steroid(60)) of pregnenolone (PREG), progesterone (P4), 17-hydroxypregnenolone (17-HPREG), 17-hydroxyprogesterone (17-HP), dehydroepiandrosterone (DHEA), and androstenedione (A4) were measured. Adrenocortical activities of 17-hydroxylase (17-OH), 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase were estimated from product to precursor ratio, using Steroid(60) values. RESULT(S): Compared with PCOS patients without AA excess, PCOS patients with AA excess demonstrated significantly greater levels of DHEA(0) and A4(60). PCOS patients with AA excess had significantly higher activity of delta(5)17-OH, compared with PCOS patients without AA excess. CONCLUSION(S): Adrenal androgen excess in PCOS is associated with a greater delta(5)17-OH activity in response to ACTH.

17-alpha-Hydroxyprogesterone↗

Prevalence of polycystic ovaries and polycystic ovary syndrome in lesbian women compared with heterosexual women.

OBJECTIVE: To determine the prevalence of polycystic ovaries (PCO) and polycystic ovarian syndrome (PCOS) in lesbian women compared with heterosexual women undergoing fertility treatment. DESIGN: A prospective observational study. SETTING: The London Women's clinic and The Hallam Medical Center. Tertiary referral fertility setup. PATIENT(S): Six hundred eighteen women undergoing ovarian stimulation with or without IUI treatment between November 2001 and January 2003. Of these, 254 were self-identified as lesbians and 364 were heterosexual women. INTERVENTION(S): Baseline pelvic ultrasound examination and blood tests conducted to measure biochemical parameters such as FSH, LH, E(2), PRL, T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS were performed between day 2 and 3 of each woman's menstrual cycle. Tubal patency tests were performed by hysterosalpingography or laparoscopy. MAIN OUTCOME MEASURE(S): Biochemical parameters. RESULT(S): Eighty percent of lesbian women, compared with 32% of the heterosexual women, had PCO on pelvic ultrasound examination. Thirty-eight percent of lesbian women, compared with 14% of heterosexual women, had PCOS. There were no significant differences in the androgen concentrations between lesbian and heterosexual women with normal ovaries. However, lesbian women with PCO and PCOS had significantly higher androgen concentrations compared with heterosexual women with PCO and PCOS. Tubal disease was as common in lesbian women as in heterosexual women. CONCLUSION(S): There is a significantly higher prevalence of PCO and PCOS in lesbian compared with heterosexual women. Lesbian women with either PCO or PCOS had more pronounced hyperandrogenism than did heterosexual women with either PCO or PCOS.

Adult↗

Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess.

OBJECTIVE: To determine whether frequencies of the mutations in the 21-hydroxylase (CYP21) gene and the G972R variant of the insulin receptor substrate-1 (IRS1) gene are increased in women with polycystic ovary syndrome (PCOS) and adrenal androgen (AA) excess. DESIGN: Prospective case-control study. SETTING: University reproductive endocrinology laboratory and outpatient clinic. PATIENT(S): Consecutive patients of non-Hispanic white race diagnosed with PCOS (n = 114) and healthy controls (n = 95). INTERVENTION(S): Blood and DNA sampling before hormonal therapy. MAIN OUTCOME MEASURE(S): Polycystic ovary syndrome patient and healthy control genotypes, with the CYP21 and IRS1 variants. RESULT(S): Fifty-four PCOS patients with (DHEAS >3000 ng/mL) and 55 without (DHEAS <2500 ng/mL) AA excess, respectively, were studied. Of 109 patients studied, 16 (14.7%) were found to be heterozygous carriers of mutations in the CYP21 gene. Of these 16, 10 (62.5%) had excessive AA secretion (i.e., excess DHEAS levels). Fifteen patients (13.8%) were found to be heterozygous carriers of the IRS1 variant; 9 (60.0%) of these 15 had excessive AA secretion. There were no significant differences in the allele frequency of CYP21 mutations or the IRS1 variant between PCOS patients with and without AA excess, and controls. None of the subjects were found to be homozygous carriers of CYP21 mutations or the IRS1 variant. Combined heterozygosity for CYP21 mutations and the IRS1 variant was limited to women with PCOS and excessive AA (n = 3). CONCLUSION(S): The G972R variant of the IRS1 gene might represent a modifier locus among women who are heterozygous carriers of CYP21 mutations, potentially increasing their risk of developing AA excess in PCOS. Nonetheless, this IRS1 variant and CYP21 mutations seem to play a limited role in the development of PCOS in the population studied.

Adrenal Glands↗

Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment.

OBJECTIVE: To determine the prevalence of insulin resistance (IR) in a large population of patients with the polycystic ovary syndrome (PCOS). DESIGN: Prospective, case-control. SETTING: University medical center. PATIENT(S): Two hundred seventy-one PCOS patients and 260 eumenorrheic, non-hirsute, control women. INTERVENTION(S): History and physical examination and blood sampling. MAIN OUTCOME MEASURE(S): Total T, free T, DHEAS, sex hormone-binding globulin, and fasting glucose and insulin levels; homeostatic model assessment values for IR (HOMA-IR) and percent beta-cell function (HOMA-%beta-cell). RESULT(S): Patients with PCOS and controls differed significantly in all parameters studied, except fasting glucose. Because the HOMA-IR and HOMA-%beta-cell values were variably associated with race, age, and body mass index, the HOMA-IR and HOMA-%beta-cell values were then adjusted for these cofounders. After adjustment, 64.4% of PCOS patients were noted to be insulin resistant, and 2.6% had beta-cell dysfunction. Compared with PCOS patients without IR (n = 96), patients with IR (n = 174) were more obese and had higher beta-cell function. CONCLUSION(S): In patients with PCOS, the prevalence of IR was 64% according to the HOMA-IR measurement, after adjustment. Patients with IR were more clinically affected. Although IR is a common abnormality in PCOS, it does not seem to be a universal feature.

Adult↗

Serum Müllerian-inhibiting substance levels in adolescent girls with normal menstrual cycles or with polycystic ovary syndrome.

OBJECTIVE: To compare serum müllerian-inhibiting substance (MIS) concentrations in adolescent girls with polycystic ovary syndrome (PCOS) or normal menstrual cycles. DESIGN: Prospective study. SETTING: University department of obstetrics and gynecology. PATIENT(S): Thirty-one girls (12-18 years old) with PCOS and 17 girls (12-19 years old) with normal menstrual cycles. INTERVENTION(S): Serum was collected from girls with PCOS or normal cycles during the early follicular phase of the menstrual cycle, stored frozen until assayed. MAIN OUTCOME MEASURE(S): Serum levels of MIS, E2, free-T, androstenedione, LH, and FSH. RESULT(S): Serum MIS levels in girls with PCOS were significantly higher compared with normal girls (4.1 +/- 2.2 [SD] and 2.4 +/- 1.0 ng/mL, respectively). The subjects were stratified for body mass index (BMI) (< and >25 kg/m2). Serum MIS levels in PCOS girls (4.2 +/- 3.0 ng/mL [BMI <25 kg/m2] and 4.0 +/- 1.6 [BMI >25 kg/m2]) were significantly higher compared with normal girls (2.2 +/- 0.8 and 2.6 +/- 0.7 ng/mL, respectively). CONCLUSION(S): Adolescent girls with PCOS have significantly higher serum MIS levels compared with normally cycling girls. Serum MIS levels in PCOS were not influenced by BMI. Increased MIS production may represent an early manifestation of the disease.

Adolescent↗

Hyperinsulinemia and circulating dehydroepiandrosterone sulfate in white and Mexican American women with polycystic ovary syndrome.

OBJECTIVE: To determine whether Mexican American women with polycystic ovary syndrome (PCOS), a population more insulin resistant than white women with PCOS, demonstrate differences in adrenal androgen production. DESIGN: Retrospective study. SETTING: University gynecology clinic and research laboratory. PATIENT(S): One hundred eleven white women and 50 Mexican American women with PCOS based on the 2003 Rotterdam Consensus Statement. INTERVENTION(S): Blood sampling, oral glucose tolerance testing, and ultrasonography. MAIN OUTCOME MEASURE(S): Serum total T, free T, DHEAS, and calculation of multiple insulin sensitivity indices after an oral glucose challenge. RESULT(S): Mexican American women with PCOS were significantly more insulin resistant than their white counterparts but had lower circulating levels of DHEAS, a reliable index of adrenal androgen production. Age and body mass index (BMI) were each inversely proportional to serum DHEAS, but no association was found between circulating insulin and serum DHEAS levels. Testosterone levels were similar between groups. CONCLUSION(S): The lower levels of DHEAS observed in the more insulin resistant Mexican American group with PCOS (compared to a similar group of white women living in the same locale) further corroborates the extent of phenotypic variability among specific PCOS populations. Hyperinsulinemia does not appear to significantly influence circulating adrenal androgen levels in PCOS.

Adult↗