A randomized double-blind controlled proof-of-concept study of alanyl-glutamine for reduction of post-myomectomy adhesions.

STUDY OBJECTIVE: To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans. DESIGN: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT). SETTING: Tertiary care gynecology surgical centre. PATIENTS: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL. INTERVENTIONS: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight. MEASUREMENTS: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG. MAIN RESULTS: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed. CONCLUSIONS: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG's known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.

A randomized controlled trial of a lifestyle intervention with longitudinal follow-up on ovarian dysmorphology in women with polycystic ovary syndrome.

OBJECTIVE: Effects of lifestyle modification on reproductive function in polycystic ovary syndrome (PCOS) remain poorly elucidated. We compared the effects of a pulse-based diet (lentils, beans, split peas and chickpeas) with Therapeutic Lifestyle Changes (TLC) diet on ultrasonographic markers of ovarian morphology, hyperandrogenism and menstrual irregularity in PCOS. DESIGN: Randomized controlled trial. PATIENTS: Women with PCOS (18-35 years). MEASUREMENTS: Thirty women randomized to the pulse-based and 31 to TLC groups completed a 16-week intervention without energy restriction. Groups performed aerobic exercise (minimum of 5 days/wk; 45 minutes/d) and received health counselling (monthly) and longitudinal follow-up. Follicle numbers per ovary (FNPO, 2-9 mm), ovarian volume (OV), free androgen index (FAI) and menstrual cycle length were measured pre- and postintervention. RESULTS: Follicle numbers per ovary (mean change ± SD, -10 ± 15), OV (-2.7 ± 4.8 mL), FAI (-3 ± 2) and menstrual cycle length (-13 ± 47 days) decreased over time in both groups (All: P < .01), without group-by-time interactions (All: P ≥ .13). Attrition rate was 33.7% and comparable between groups (P = .94). Adherence to diet intervention negatively correlated with changes in FNPO (r=-0.54), OV (r=-0.35) and FAI (r = -.29) in pooled groups (All: P ≤ .04). Groups maintained reduced OV, FNPO, FAI and menstrual cycles 6 months postintervention; however, decreased FNPO and FAI at 16 weeks tended to revert to baseline levels 12 months postintervention in both groups (All: P ≤ .05). CONCLUSIONS: Both interventions improved ovarian dysmorphology, hyperandrogenism and menstrual irregularity in PCOS, and no diet appeared to be superior at improving reproductive outcomes. Our observations highlight the importance of longitudinal surveillance for sustainable adherence to newly adopted healthy lifestyle behaviours and reproductive health in PCOS (ClinicalTrials.gov identifier, NCT01288638).

Effect of a pulse-based diet and aerobic exercise on bone measures and body composition in women with polycystic ovary syndrome: A randomized controlled trial.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with clinical symptoms including menstrual dysfunction and hyperandrogenemia, as well as insulin resistance which is thought to be a key contributing factor to symptoms. Insulin is also thought to positively affect bone while oligo- and amenorrhea are known to negatively affect bone. Lifestyle modification is the first recommendation to treat symptoms of PCOS; however, little is known about the effect of lifestyle interventions on bone measures in this population. Pulses (e.g., chickpeas, beans, split peas, lentils) have been shown to lower fasting insulin, and the objective of this study was to determine the effect of a pulse-based diet compared to the therapeutic lifestyle changes (TLC) diet on bone measures and body composition in women with PCOS. Women aged 18-35 years with PCOS were randomized to either a pulse-based diet or the TLC diet for 16-weeks while following an aerobic exercise program. Thirty-one in the TLC group and 29 in the pulse group completed dual-energy X-ray absorptiometry analysis following the intervention. After 16-weeks, both groups had a lower BMI, whole body fat mass, and % fat (p < 0.005), with no difference in lean mass. In both groups, lumbar spine bone mineral content (BMC) and density were higher following the intervention (p < 0.05) while femoral neck bone mineral density (BMD) was lower (p < 0.05). Intertrochanteric section modulus improved in both groups while there was a group x time interaction in femoral shaft subperiosteal width which was more favorable in the pulse group (p < 0.05). This study demonstrates that the femoral neck may be compromised during a lifestyle intervention in women with PCOS. Research is warranted to preserve bone health during lifestyle change in women with PCOS.

A pulse-based diet and the Therapeutic Lifestyle Changes diet in combination with health counseling and exercise improve health-related quality of life in women with polycystic ovary syndrome: secondary analysis of a randomized controlled trial.

Objective: A favorable dietary composition to increase health-related quality of life (HRQoL) in PCOS remains unclear. We compared changes in HRQoL of women with PCOS who participated in a low-glycemic-index pulse-based (lentils, beans, split peas, and chickpeas) or the Therapeutic Lifestyle Changes (TLC) diet intervention.Methods: Thirty women in the pulse-based and 31 in the TLC groups (18-35 years) completed a 16-week intervention without energy-restriction. Groups participated in health counseling (monthly) and aerobic exercise (5 days/week; 45 minutes/day).Results: Fifty-five (90.2%) women completed a PCOS-specific HRQoL survey. Greatest mean increases in time-effects occurred in the domains of healthy eating, PCOS knowledge, active living, healthcare satisfaction, feelings and experiences about intervention, and health concerns, respectively (p ≤ 0.02), without group-by-time interactions (p ≥ 0.13). Decreased weight (r = -0.35) and homeostatic model assessment of insulin resistance (r = -0.18) correlated with increased scores of PCOS knowledge; adherence to intervention correlated with increased scores of active living (r = 0.39) and healthy eating (r = 0.53; p ≤ 0.03).Conclusions: Both interventions improved HRQoL scores in women with PCOS without prescribed energy-restriction. Our observations add novel insights into current evidence and elucidate the need for future psychological research to target lifestyle modifications for improving HRQoL and unique psychological complications of PCOS in this high-risk population (CinicalTrials.gov identifier:NCT01288638).

Dysglycemia, Not Altered Sex Steroid Hormones, Affects Cognitive Function in Polycystic Ovary Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex endocrine condition characterized by multiple reproductive and metabolic abnormalities. Because individual reproductive and metabolic abnormalities modulate working memory in the general population, there is growing interest in whether cognitive function is dually and negatively affected in PCOS. OBJECTIVE: To examine the association of reproductive and metabolic features with cognitive function in women with and without PCOS. DESIGN: An observational, cross-sectional study was conducted at an academic clinical research center in North America between 2006 and 2009. Common tests of working memory (i.e., manual dexterity, perceptual speed, and visuospatial ability) were performed by women with PCOS (n = 40) and control subjects (n = 40). Markers of sex steroid hormones, ovulatory function, and cardiometabolic health were also assessed. RESULTS: Reduced visuospatial ability was observed in women with PCOS compared with control subjects (P < 0.01). Reduced visuospatial ability was linked to higher levels of hemoglobin A1c in the entire study cohort, independent of body mass index or PCOS status. No associations were observed between visuospatial ability and reproductive features, after controlling for confounding variables. CONCLUSION: Our findings support a role for glycemic control, and not PCOS per se, in cognitive dysfunction in women of reproductive age. Additional studies are needed to understand the short- and long-term effects of dysglycemia on brain health in women with PCOS, given their increased propensity for metabolic comorbidities, compared with control subjects.

Impact of right-left differences in ovarian morphology on the ultrasound diagnosis of polycystic ovary syndrome.

OBJECTIVE: To assess right-left differences in ultrasonographic markers of ovarian morphology and determine the impact on the diagnosis of polycystic ovarian morphology (PCOM). DESIGN: A cross-sectional study of data collected from 2006 to 2018. SETTING: Academic clinical research centers. PATIENT(S): Women with polycystic ovary syndrome (PCOS; n = 87) and controls (n = 67). INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Follicle number per ovary (FNPO), follicle number per cross-section (FNPS), and ovarian volume (OV) were assessed in both ovaries using transvaginal ultrasonography. PCOM was identified based on recent international consensus guidelines or proposed diagnostic thresholds. RESULT(S): Overall, mean right-left differences were two follicles for FNPO, one follicle for FNPS, and 2 mL for OV. FNPO showed the strongest correlation between ovaries. Its assessment in a single ovary did not impact the diagnosis of PCOM in women with PCOS. However, there were differences in the probability of unilateral versus bilateral PCOM based on FNPS and OV in both groups. CONCLUSION(S): FNPO is the most reliable unilateral marker of PCOM in light of right-left differences in ovarian morphology. Use of FNPS or OV to define PCOM is discouraged when only one ovary is visualized.

Polycystic ovary syndrome is a risk factor for sarcopenic obesity: a case control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in young women and increases risk of cardiovascular and metabolic disease, and infertility. Women with PCOS share many characteristics commonly associated with aging including chronic inflammation and insulin resistance, which may be associated with "sarcopenic obesity", a term used to describe low appendicular skeletal muscle mass relative to total body mass. The purpose of this work was to determine the prevalence of sarcopenic obesity in women with PCOS. We hypothesized there would be a high prevalence of sarcopenic obesity, and that % appendicular skeletal muscle mass and markers of inflammation and insulin resistance would be inversely correlated in this population. METHODS: Dual energy X-ray absorptiometry was used to assess body composition in 68 women with PCOS aged 18-35y and 60 healthy age-matched women from the same geographic area. Sarcopenic obesity was defined as having % appendicular skeletal muscle mass 2 standard deviations below the mean for the healthy age-matched controls and a % body fat above 35%. Data were analyzed with Mann-Whitney U-tests and Spearman correlations. RESULTS: 53% of women with PCOS were classified as sarcopenic obese. Women with PCOS had a median (interquartile range) appendicular skeletal muscle mass of 23.8 (22.3-25.8)% which was lower than the control median of 30.4 (28.6-32.4)% (p < 0.0001). Among women with PCOS, there were negative correlations between % appendicular skeletal muscle mass and the homeostasis model assessment insulin resistance index (r = - 0.409; p < 0.01), high sensitivity C-reactive protein (r = - 0.608; p < 0.0001) and glycosylated hemoglobin (r = - 0.430; p < 0.0001). Furthermore, % appendicular skeletal muscle mass correlated positively with vitamin D (r = 0.398; p < 0.0001) in women with PCOS, which is thought to positively affect skeletal muscle mass. CONCLUSIONS: Women with PCOS have a high prevalence of sarcopenic obesity, which is correlated to insulin resistance and inflammation.

Comprehensive Evaluation of Type 2 Diabetes and Cardiovascular Disease Risk Profiles in Reproductive-Age Women with Polycystic Ovary Syndrome: A Large Canadian Cohort.

OBJECTIVE: This study compared the prevalence of metabolic syndrome (MetS) and characterized type 2 diabetes (DM2) and cardiovascular disease (CVD) risk profiles between Canadian women with polycystic ovary syndrome (PCOS) and healthy women recruited from the general population. Furthermore, within the PCOS cohort, the study contrasted the CVD and DM2 risk profiles of women with or without MetS. METHODS: Measures of MetS (International Diabetes Federation; National Heart, Lung, and Blood Institute; and the American Heart Association definition), DM2 (Diabetes Canada Clinical Guidelines), and CVD risk factors (Androgen Excess and Polycystic Ovary Syndrome Society statement) were evaluated for 237 women with PCOS (Androgen Excess and PCOS Society definitions) and 42 controls (aged 18-36) in a prospective observational study (Canadian Task Force Classification II-2). RESULTS: The prevalence of MetS was 29.5% in the PCOS group, which was approximately six-fold higher than age-matched controls (P < 0.001). Women with PCOS exhibited higher glucose abnormality, acanthosis nigricans, total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C), and lower sex hormone-binding globulin concentrations when compared with controls after accounting for differences in the BMI (P < 0.01). Further, women with PCOS and MetS exhibited exacerbated insulin and glucose responses to a 75-g oral glucose tolerance test and greater acanthosis nigricans, hirsutism, TC/HDL-C, TC, and sex hormone-binding globulin concentrations compared with their BMI-adjusted counterparts without MetS (P < 0.05). CONCLUSION: Canadian reproductive-age women with PCOS have a high prevalence of MetS and exhibit adverse cardiometabolic risk factors that warrant early screening and regular monitoring across their reproductive lifespan.

A Comparison of a Pulse-Based Diet and the Therapeutic Lifestyle Changes Diet in Combination with Exercise and Health Counselling on the Cardio-Metabolic Risk Profile in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.

We compared the effects of a low-glycemic index pulse-based diet, containing lentils, beans, split peas, and chickpeas, to the Therapeutic Lifestyle Changes (TLC) diet on cardio-metabolic measures in women with polycystic ovary syndrome (PCOS). Ninety-five women (18⁻35 years) enrolled in a 16-week intervention; 30 women in the pulse-based and 31 in the TLC groups completed the study. Women participated in aerobic exercise training (minimum 5 days/week for 45 min/day) and were counselled (monthly) about PCOS and lifestyle modification. Women underwent longitudinal follow-up post-intervention. The pulse-based group had a greater reduction in total area under the curve for insulin response to a 75-g oral glucose tolerance test (mean change ± SD: -121.0 ± 229.9 vs. -27.4 ± 110.2 µIU/mL × min; p = 0.05); diastolic blood pressure (-3.6 ± 6.7 vs. -0.2 ± 6.7 mmHg, p = 0.05); triglyceride (-0.2 ± 0.6 vs. 0.0 ± 0.5 mmol/L, p = 0.04); low-density lipoprotein cholesterol (-0.2 ± 0.4 vs. -0.1 ± 0.4 mmol/L, p = 0.05); total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C; -0.4 ± 0.4 vs. 0.1 ± 0.4, p < 0.001); and a greater increase in HDL-C (0.1 ± 0.2 vs. -0.1 ± 0.2 mmol/L, p < 0.01) than the TLC group. Decreased TC/HDL-C (p = 0.02) at six-month and increased HDL-C and decreased TC/HDL-C (p ≤ 0.02) at 12-month post-intervention were maintained in the pulse-based group. A pulse-based diet may be more effective than the TLC diet at improving cardio-metabolic disease risk factors in women with PCOS. TRIAL REGISTRATION: CinicalTrials.gov identifier, NCT01288638.

Women With Polycystic Ovary Syndrome Have Comparable Hip Bone Geometry to Age-Matched Control Women.

Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting women of reproductive age manifesting with polycystic ovaries, menstrual irregularities, hyperandrogenism, hirsutism, and insulin resistance. The oligomenorrhea and amenorrhea characteristic to PCOS are associated with low bone mineral density (BMD); conversely, the hyperandrogenism and hyperinsulinemia may elicit a protective effect on BMD. As bone geometric properties provide additional information about bone strength, the objective of this study was to compare measures of hip geometry in women with PCOS to a healthy female population. Using dual-energy X-ray absorptiometry, BMD and measures of hip geometry were determined in women with PCOS (n = 60) and healthy controls (n = 60) aged 18-35 years. Clinical biochemical measures were also determined in women with PCOS. Measures of hip geometry, including cross-sectional area, cross-sectional moment of inertia, subperiosteal width (SPW), and section modulus, were similar between groups following correction for body mass index (BMI) (all p > 0.05) with intertrochanter SPW significantly lower in women with PCOS (p < 0.05). BMI-corrected whole body BMD as well as the lumbar spine and regions of proximal femur were also comparable between groups. In women with PCOS, BMI-corrected correlations were found between insulin and femoral shaft SPW (r = 0.322, p < 0.05), glucose and femoral neck (r = 0.301, p < 0.05), and trochanter BMD (0.348, p < 0.05), as well as between testosterone and femoral neck BMD (0.376, p < 0.05) and narrow neck cross-sectional area (0.306, p < 0.05). This study demonstrates that women with PCOS may have compromised intertrochanter SPW while oligomenorrhea appears to have no detrimental effect on bone density or geometry in women with PCOS.

The role of a pulse-based diet on infertility measures and metabolic syndrome risk: protocol of a randomized clinical trial in women with polycystic ovary syndrome.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is an endocrine disorder in women of reproductive age with an estimated prevalence of 5-20% of premenopausal women. The clinical symptoms common to PCOS include menstrual dysfunction, hyperandrogenemia, hirsutism, polycystic ovaries, insulin resistance, and hyperinsulinemia. Women with PCOS are at an increased risk of infertility, obesity and type 2 diabetes mellitus. Insulin resistance and hyperinsulinemia are believed to be key contributing factors to the pathogenesis of PCOS; excessive amounts of insulin are directly associated with the increased ovarian production of androgens and metabolic features of PCOS. Pulse-based diets (e.g., beans, chickpeas) are associated with improved glycemic control and have insulin lowering effects. The purpose of this study is to determine whether a pulse-based diet is more effective than the diet recommended by the National Cholesterol Education Program. The primary outcomes of this study are disease measures related to PCOS, with secondary outcomes including measures related to metabolic syndrome. METHODS: Women with symptoms of PCOS will be recruited for the study and a diagnosis of PCOS will be determined by an obstetrician-gynecologist. Women with PCOS will be randomly assigned to receive either a pulse-based diet or the National Cholesterol Education Program therapeutic lifestyle changes (TLC) diet for 16 weeks while participating in an aerobic exercise program. One hundred participants will be required (drop-out rate of 32%) for recruitment to provide 80% power for detecting a significant difference in fasting glucose (p < 0.05). Measures related to infertility, metabolic syndrome, quality of life, dietary intake and physical activity will be assessed pre- and post-intervention with follow up assessment at 6- and 12-months post-intervention. DISCUSSION: Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age and there is currently no recommended diet for this population of women. The multidisciplinary nature of this study, including determination of measures related to metabolic syndrome, infertility and physical activity provide a comprehensive assessment of any benefits associated with a pulse-based diet in women with PCOS. The results of this study will help in providing evidence-based recommendations for the optimum diet to reduce symptoms associated with PCOS. TRIAL REGISTRATION: NCT01288638. Trial registered January 13, 2011.

Ultrasound features of polycystic ovaries relate to degree of reproductive and metabolic disturbance in polycystic ovary syndrome.

OBJECTIVE: To reexamine associations between polycystic ovarian morphology (PCOM) and degree of symptomatology in polycystic ovary syndrome (PCOS) using a well-defined PCOS population, newer ultrasound technology, and reliable offline assessments of sonographic parameters. DESIGN: Cross-sectional observational study. SETTING: Academic hospital and clinical research unit. PATIENT(S): Forty-nine women with PCOS as defined by hyperandrogenism and oligoamenorrhea. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of follicles per follicle size category, antral follicle count (AFC), ovarian volume (OV), follicle distribution pattern, stromal area, ovarian area, stromal to ovarian area ratio (S/A) and stromal echogenicity index (SI), total (TT), androstenedione, LH, FSH, cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, C-reactive protein, glucose, insulin, and hemoglobin A1C, menstrual cycle length, hirsutism score, body mass index (BMI), waist:hip ratio, and blood pressure. RESULT(S): AFC, but not OV, was positively associated with TT (ρ = .610), androstenedione (ρ = .490), and LH:FSH (ρ = .402). SI was positively associated with androgen markers and LH:FSH, while S/A was negatively associated with these variables. Follicles ≤4 mm were negatively associated with various metabolic markers, whereas larger follicles (5-8 mm) showed positive associations. Stromal markers were not associated with cardiometabolic measures. LH:FSH best predicted follicles ≤4 mm, and BMI predicted 5- to 9-mm follicles. Dominant follicles ≥10 mm were best predicted by age. CONCLUSION(S): AFC, and not OV, reflected the severity of reproductive dysfunction in PCOS. Associations among different sized follicles were consistent with recruitable sized follicles, which reflects the severity of metabolic dysfunction in PCOS.

Recombinant human luteinizing hormone to trigger ovulation: randomized, controlled, dose-finding pilot study in ovulation induction.

OBJECTIVE: To evaluate recombinant human luteinizing hormone (r-hLH) versus urine-derived human chorionic gonadotropin (u-hCG) to trigger ovulation in women (aged 20-40 years) with WHO Group II anovulatory infertility undergoing ovulation induction (OI) with recombinant human follicle-stimulating hormone (r-hFSH) (150 IU/day starting dose). STUDY DESIGN: For this Phase II, open-label, dose-finding pilot study, patients were randomized to doses of 825, 2,750, 5,500, 11,000, or 22,000 IU r-hLH or u-hCG (5,000 IU). Primary endpoints were ovulation and ratio of ruptured follicles/follicle > or = 15 mm (day of r-hLH/ u-hCG administration). Secondary endpoints included monofollicular ovulation and clinical pregnancy rates. RESULTS: All 67 randomized patients completed treatment. All patients in the r-hLH 2,750 (13/13), 5,500 (12/ 12), 11,000 IU (13/13), and u-hCG 5,000 IU (12/ 12) groups ovulated; 3/5 patients in the r-hLH 825 IU and 2/12 in the r-hLH 22,000 IU group failed to ovulate (p = 0.105 between evaluable groups). The mean ratio of ruptured follicles/ follicle > or = 15 mm was 1.1 (p = 0.675 between groups). The monofollicular ovulation rate was 15/60 (25%). Two cases of ovarian hyperstimulation syndrome were reported. CONCLUSION: This open-label, pilot study (conducted in 1999-2001) suggests that the minimal effective dose of r-hLH to trigger ovulation in women with WHO Group II anovulatory infertility undergoing OI with r-hFSH (150 IU starting dose) was 2,750 IU.

Prevalence of Polycystic Ovary Syndrome Phenotypes Using Updated Criteria for Polycystic Ovarian Morphology: An Assessment of Over 100 Consecutive Women Self-reporting Features of Polycystic Ovary Syndrome.

The prevalence of polycystic ovary syndrome (PCOS) and its distinct clinical phenotypes were assessed using 3 sets of international diagnostic criteria in women self-reporting concerns over outward features of PCOS. Revised ultrasonographic criteria for polycystic ovaries (PCO) based on modern ultrasound technology were used. Of the participants, 53%, 62%, and 70% were diagnosed with PCOS using National Institutes of Health, Androgen Excess and PCOS Society, and Rotterdam criteria, respectively. Prevalence of Frank, Ovulatory, Normoandrogenic, and Non-PCO PCOS were 66%, 13%, 11%, and 9%, respectively. Frank PCOS was associated with the severest metabolic disturbances whereas metabolic profiles in Normoandrogenic PCOS did not differ from controls, supporting reduced health risks in women without androgen excess. Metabolic disturbances and hyperandrogenism were linked to excess adiposity across all the groups. Using updated criteria for PCO, the prevalence of Non-PCO PCOS and PCO alone in healthy women recruited from the general population was reduced compared to the previous reports.

Follicle number, not assessments of the ovarian stroma, represents the best ultrasonographic marker of polycystic ovary syndrome.

OBJECTIVE: To compare the diagnostic potential of ultrasonographic markers of ovarian morphology, used alone or in combination, to predict polycystic ovary syndrome (PCOS). DESIGN: A diagnostic test study using cross-sectional data collected from 2006-2011. SETTING: Academic hospital and clinical research unit. PATIENT(S): Eighty-two women with PCOS and 60 healthy female volunteers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follicle number per ovary (FNPO), ovarian volume (OV), follicle number per single cross-section (FNPS), follicle distribution pattern, stromal area, ovarian area, stromal-to-ovarian area ratio (S:A), and stromal index (SI). RESULT(S): Follicle number per ovary best predicted PCOS (R(2) = 67%) with 85% sensitivity and 98% specificity, followed by OV (R(2) = 44%), and FNPS (R(2) = 36%). Neither S:A nor SI had predictive power for PCOS. In combination, FNPO+S:A and FNPO+SI most significantly predicted PCOS (R(2) = 74% vs. 73%, respectively). The diagnostic potentials of OV and FNPS were substantially improved when used in combination (OV+FNPO, R(2) = 55%). CONCLUSION(S): As a single metric, FNPO best predicted PCOS. Although the addition of S:A or SI improved the predictive power of FNPO, gains were marginal, suggesting limited use in clinical practice. When image quality precludes a reliable estimation of FNPO, measurements of OV+FNPS provide the next closest level of diagnostic potential.

Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume.

STUDY QUESTION: Do the ultrasonographic criteria for polycystic ovaries supported by the 2003 Rotterdam consensus adequately discriminate between the normal and polycystic ovary syndrome (PCOS) condition in light of recent advancements in imaging technology and reliable methods for estimating follicle populations in PCOS? STUDY ANSWER: Using newer ultrasound technology and a reliable grid system approach to count follicles, we concluded that a substantially higher threshold of follicle counts throughout the entire ovary (FNPO)-26 versus 12 follicles-is required to distinguish among women with PCOS and healthy women from the general population. WHAT IS KNOWN ALREADY: The Rotterdam consensus defined the polycystic ovary as having 12 or more follicles, measuring between 2 and 9 mm (FNPO), and/or an ovarian volume (OV) >10 cm(3). Since their initial proposal in 2003, a heightened prevalence of polycystic ovaries has been described in healthy women with regular menstrual cycles, which has questioned the accuracy of these criteria and marginalized the specificity of polycystic ovaries as a diagnostic criterion for PCOS. STUDY DESIGN, SIZE, DURATION: A diagnostic test study was performed using cross-sectional data, collected from 2006 to 2011, from 168 women prospectively evaluated by transvaginal ultrasonography. Receiver operating characteristic (ROC) curve analyses were performed to determine the appropriate diagnostic thresholds for: (i) FNPO, (ii) follicle counts in a single cross section (FNPS) and (iii) OV. The levels of intra- and inter-observer reliability when five observers used the proposed criteria on 100 ultrasound cases were also determined. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ninety-eight women diagnosed with PCOS by the National Institutes of Health criteria as having both oligo-amenorrhea and hyperandrogenism and 70 healthy female volunteers recruited from the general population. Participants were evaluated by transvaginal ultrasonography at the Royal University Hospital within the Department of Obstetrics, Gynecology and Reproductive Sciences, University of Saskatchewan (Saskatoon, SK, Canada) and in the Division of Nutritional Sciences' Human Metabolic Research Unit, Cornell University (Ithaca, NY, USA). MAIN RESULTS: Diagnostic potential for PCOS was highest for FNPO (0.969), followed by FNPS (0.880) and OV (0.873) as judged by the area under the ROC curve. An FNPO threshold of 26 follicles had the best compromise between sensitivity (85%) and specificity (94%) when discriminating between controls and PCOS. Similarly, an FNPS threshold of nine follicles had a 69% sensitivity and 90% specificity, and an OV of 10 cm(3) had a 81% sensitivity and 84% specificity. Levels of intra-observer reliability were 0.81, 0.80 and 0.86 when assessing FNPO, FNPS and OV, respectively. Inter-observer reliability was 0.71, 0.72 and 0.82, respectively. LIMITATIONS, REASONS FOR CAUTION: Thresholds proposed by this study should be limited to use in women aged between 18 and 35 years. WIDER IMPLICATIONS OF THE FINDINGS: Polycystic ovarian morphology has excellent diagnostic potential for detecting PCOS. FNPO have better diagnostic potential and yield greater diagnostic confidence compared with assessments of FNPS or OV. Whenever possible, images throughout the entire ovary should be collected for the ultrasonographic evaluation of PCOS. STUDY FUNDING AND COMPETING INTEREST: This study was funded by Cornell University and fellowship awards from the Saskatchewan Health Research Foundation and Canadian Institutes of Health Research. The authors have no conflict of interests to disclose.

Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome.

BACKGROUND: We recently showed that women with four clinical phenotypes of polycystic ovary syndrome (PCOS) do not demonstrate anatomical evidence of elevated prenatal androgen exposure as judged by a lower ratio of the index (2D) to ring (4D) finger. However, those findings conflicted with a previous study where women with PCOS had lower right hand 2D:4D compared to healthy female controls. Both these studies used Vernier calipers to measure finger lengths--a method recently shown to be less reliable at obtaining finger length measurements than computer-assisted analysis. METHODS: Ninety-six women diagnosed with PCOS according to the 2003 Rotterdam criteria had their finger lengths measured with computer-assisted analysis. Participants were categorized into four recognized phenotypes of PCOS and their 2D:4D compared to healthy female controls (n = 48) and men (n = 50). RESULTS: Digit ratios assessed by computer-assisted analysis in women with PCOS did not differ from female controls, but were significantly lower in men. When subjects were stratified by PCOS phenotype, 2D:4D did not differ among phenotypes or when compared to female controls. CONCLUSION: Computer-assisted measurements validated that digit ratios of women with PCOS do not show anatomical evidence of increased prenatal androgen exposure.

Women's perceptions of polycystic ovary syndrome following participation in a clinical research study: implications for knowledge, feelings, and daily health practices.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects 6% to 10% of reproductive aged women. It is a poorly understood and often undiagnosed condition that has implications for the health of affected women. We assessed changes in knowledge, feelings, and daily health practices related to PCOS in clinical research study participants. METHODS: Sixty-eight women who had received counselling and education about PCOS while participating in a clinical research study were invited to complete an online survey that assessed levels of concern, knowledge, healthy dieting, active living, and health care satisfaction before and after the study. Differences and associations between scores were analyzed by paired t tests and Pearson correlation. RESULTS: Forty-three women (63%) completed the survey. After taking part in a clinical research study, participants believed they had increased knowledge of (P < 0.001) and concern about (P = 0.029) the etiology and health consequences of PCOS, better lifestyle practices (P < 0.001), and improved health care satisfaction (P = 0.045). Enhanced knowledge of PCOS was positively associated with changes in concern (P = 0.045), healthy dietary habits (P = 0.04), activity levels (P = 0.003), and health care satisfaction (P < 0.001). After the study, women felt empowered to participate in the management of their condition and communicate with their primary care providers. CONCLUSION: Women with PCOS felt that they had more knowledge and motivation to implement preventive health strategies after participating in a clinical research study. Education about how PCOS affects their immediate and long-term health enabled women with PCOS to feel physical and psychological benefits and to engage more with their health care providers.

Grid analysis improves reliability in follicle counts made by ultrasonography in women with polycystic ovary syndrome.

Poor reliability has been reported when counting the total number of follicles in polycystic ovaries using conventional two-dimensional (2-D) ultrasound viewing methods. In the current study, we report good reliability in follicle counts when observers imposed a programmable grid system over the viewing window. Four observers estimated total follicle counts in 45 ovarian ultrasound scans by compartmentalizing the ovary into 9 to 12 grid sections and performing focused follicle counts per section. The mean number of follicles counted per ovary was 44.6 +/- 2.3. The level of inter-observer agreement when making follicle counts was 0.82 and total follicle counts did not differ among observers. The level of intra-observer agreement was 0.93 which further corroborated the utility of this method for making dependable follicle counts. In summary, the ability to obtain reproducible follicle counts will help to establish reliable diagnostic criteria for polycystic ovarian morphology.

Digit ratios do not serve as anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is heterogeneous in its clinical presentation and four major phenotypes have been identified. The precise etiology of PCOS is unknown; however, variable exposure to prenatal androgens may be responsible for the spectrum of endocrine and metabolic disturbances characteristic of this syndrome. Since prenatal testosterone exposure is known to decrease the ratio of the second to fourth finger lengths (2D:4D), we characterized the left and right hand 2D:4D in women with clinical variants of PCOS. We hypothesized that if prenatal androgens were involved in the development of the phenotypic spectrum of PCOS, then lower 2D:4D would be differentially expressed among clinical variants of the syndrome. METHODS: Digit ratios were determined in 98 women diagnosed with PCOS by the 2003 international consensus guidelines and in 51 women with regular menstrual cycles, no clinical or biochemical signs of hyperandrogenism and normal ovarian morphology. Women with PCOS were categorized into four clinical phenotypes (i.e. Frank, Non-PCO, Ovulatory and Mild) and 2D:4D among groups were compared by Tukey-Kramer multiple comparisons tests. RESULTS: Left (P = 0.77) and right (P = 0.68) hand 2D:4D were similar among the four clinical phenotypes and no phenotype of PCOS demonstrated a 2D:4D that differed from controls (Left Hand, P = 0.44 and Right Hand, P = 0.75). CONCLUSIONS: Women with PCOS do not demonstrate finger length patterns that are consistent with increased prenatal androgen exposure. These findings do not preclude a role for prenatal androgens in the development of PCOS; however, low 2D:4D are not a characteristic of PCOS.