Impact of a hypocaloric dietary intervention on antral follicle dynamics in eumenorrheic women with obesity.

STUDY QUESTION: Do antral follicle dynamics change in women with obesity and regular ovulatory cycles after a 6-month hypocaloric dietary intervention? SUMMARY ANSWER: After a 6-month hypocaloric dietary intervention, women with obesity and regular ovulatory cycles displayed evidence of improved antral follicle dynamics defined by the emergence of more dominant follicles, larger ovulatory follicle diameter at selection, and increased luteal progesterone concentrations compared to pre-intervention. WHAT IS KNOWN ALREADY: Precise events in antral folliculogenesis must occur in order for natural and regular monthly ovulation. In healthy women of reproductive age, antral follicles are recruited for growth in a wave-like fashion, wherein a subset of follicles are selected for preferential growth, and typically, one dominant follicle culminates in ovulation. Women with obesity and regular ovulatory cycles display evidence of suppressed antral follicle development, as evidenced by fewer recruitment events, fewer selectable and dominant follicles, smaller diameter of the ovulatory follicle at selection, and a higher prevalence of luteal phase defects. While improvements in gonadotropin and ovarian steroid hormone concentrations after weight loss have been documented in eumenorrheic women with obesity, the precise impact of weight loss on antral follicle dynamics has not been evaluated. STUDY DESIGN, SIZE, DURATION: A pre-post pilot study of 12 women who participated in a 6-month hypocaloric dietary intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twelve women with obesity (total body fat ≥35%) underwent transvaginal ultrasonography and venipuncture every-other-day for one inter-ovulatory interval (IOI) both before (baseline) and during the final month (Month 7) of a six-month hypocaloric dietary intervention. Participants were aged 24-34 years and had a self-reported history of regular menstrual cycles (25-35 days). Follicle number and diameter (≥2 mm) were quantified at each study visit, and individual growth profiles for all follicles ≥7 mm were determined. Blood samples were assayed for reproductive hormones. Follicle dynamics and reproductive hormone concentrations were compared pre- and post-intervention. Further, post-intervention follicle and endocrine dynamics (Month 7 IOI) were compared to an age-matched reference cohort of lean women with regular ovulatory cycles (total body fat <35%, N = 21). MAIN RESULTS AND THE ROLE OF CHANCE: Participants lost an average of 11% of their original body weight with the hypocaloric dietary intervention. More dominant follicles were detected (≥10 mm) at Month 7 compared to baseline (0. 3 ± 0.4 versus 0.4 ± 0.5 follicles, P = 0.001), and ovulatory follicles were selected at larger diameters post-intervention (7.3 ± 2.0 versus 10.9 ± 2.6 mm, P = 0.007). Luteal progesterone concentrations were increased at Month 7 compared to baseline (5.3 ± 3.65 versus 6.3 ± 4.74 ng/ml, P < 0.0001). However, risk for luteal phase dysfunction as judged by the prevalence of a luteal phase length <10 days, integrated luteal progesterone levels <80 ng/ml or peak progesterone <10 ng/ml did not differ pre- versus post-intervention (all, P > 0.05). In Month 7, follicle dynamics and endocrine profiles were similar to the reference cohort across all measures. LIMITATIONS, REASONS FOR CAUTION: This study does not inform on the earliest stages of ovarian follicle development and is limited to providing knowledge on the later stages of antral follicle development. This study cannot fully address causation between weight loss and sustained improvements in antral follicle dynamics. The data cannot be extrapolated to comment on potential improvements in fertility and fecundity with weight loss. The small group sizes limit statistical power. WIDER IMPLICATIONS OF THE FINDINGS: The increasing prevalence of obesity necessitates an understanding of the mechanisms that underlie potential improvements in reproductive health outcomes with weight loss. Women with obesity and regular ovulatory cycles who undertook a 6-month hypocaloric dietary intervention demonstrated improvements consistent with benefits of lifestyle intervention on reproductive health even in those without overt signs of reproductive dysfunction. Potential improvements in the cellular makeup of follicles, which may underlie the restoration of normal follicle development and amelioration of subfertility, require further investigation. STUDY FUNDING/COMPETING INTEREST(S): Cornell University, President's Council of Cornell Women, United States Department of Agriculture (Grant No. 8106), and National Institutes of Health (R01-HD0937848). B.Y.J. and H.V.B. were supported by doctoral training awards from the National Institutes of Health (T32-DK007158) and Canadian Institutes of Health Research (Grant No. 146182), respectively. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NCT01927432 and NCT01785719.

Ultrasonographic criteria in the diagnosis of polycystic ovary syndrome: a systematic review and diagnostic meta-analysis.

BACKGROUND: Polycystic ovary morphology (PCOM) on ultrasonography is considered as a cardinal feature of polycystic ovarian syndrome (PCOS). Its relevance as a diagnostic criterion for PCOS was reaffirmed in the most recent International Evidence-Based Guideline for the Assessment and Management of PCOS. However, there remains a lack of clarity regarding the best practices and specific ultrasonographic markers to define PCOM. OBJECTIVE AND RATIONALE: The aim of this systematic review and diagnostic meta-analysis was to assess the diagnostic accuracy of various ultrasonographic features of ovarian morphology in the diagnosis of PCOS. SEARCH METHODS: Relevant studies published from 1 January 1990 to 12 June 2023 were identified by a systematic search in PubMed, Web of Science, Scopus, CINAHL, and CENTRAL. Studies that generated diagnostic accuracy measures (e.g. proposed thresholds, sensitivity, specificity) for PCOS using the following ultrasonographic markers met criteria for inclusion: follicle number per ovary (FNPO) or per single cross-section (FNPS), ovarian volume (OV), and stromal features. Studies on pregnant or post-menopausal women were excluded. Risk of bias and applicability assessment for diagnostic test accuracy studies were determined using the QUADAS-2 and QUADAS-C tool for a single index test or between multiple index tests, respectively. Diagnostic meta-analysis was conducted using a bivariate model of pooled sensitivity and specificity, and visualized using forest plots and summary receiver-operating characteristic (SROC) curves. OUTCOMES: From a total of 2197 records initially identified, 31 studies were included. Data from five and two studies were excluded from the meta-analysis due to duplicate study populations or limited data for the index test, leaving 24 studies. Pooled results of 20 adult studies consisted of 3883 control participants and 3859 individuals with PCOS. FNPO was the most accurate diagnostic marker (sensitivity: 84%, CI: 81-87%; specificity: 91%, CI: 86-94%; AUC: 0.905) in adult women. OV and FNPS had similar pooled sensitivities (OV: 81%, CI: 76-86%; FNPS: 81%, CI: 70-89%) but inferior pooled specificities (OV: 81%, CI: 75-86%; FNPS: 83%, CI: 75-88%) and AUCs (OV: 0.856; FNPS: 0.870) compared to FNPO. Pooled results from four adolescent studies consisting of 210 control participants and 268 girls with PCOS suggested that OV may be a robust ultrasonographic marker for PCOS diagnosis albeit the current evidence remains limited. The majority of the studies had high risk of bias for the patient selection (e.g. lack of randomized/consecutive patient selection) and index test (e.g. lack of pre-proposed thresholds for comparison) domains across all ultrasonographic markers. As such, diagnostic meta-analysis was unable to determine the most accurate cutoff for ultrasonographic markers to diagnose PCOS. Subgroup analysis suggested that stratification based on previously proposed diagnostic thresholds, age, BMI, or technology did not account for the heterogeneity in diagnostic accuracy observed across the studies. Studies that diagnosed PCOS using the Rotterdam criteria had improved sensitivity for FNPO. Studies from North America had lower diagnostic accuracy when compared to Asian studies (FNPO: sensitivity) and European studies (OV: specificity, diagnostic odds ratio and positive likelihood ratio). Geographic differences in diagnostic accuracy may potentially be due to differences in age, BMI, and diagnostic criteria of the PCOS group across regions. WIDER IMPLICATIONS: This diagnostic meta-analysis supports the use of FNPO as the gold standard in the ultrasonographic diagnosis of PCOS in adult women. OV and FNPS provide alternatives if total antral follicle counts cannot be accurately obtained. Our findings support the potential for ultrasonographic evidence of PCOM in adolescents as more data becomes available. Subgroup analysis suggests the need to investigate any relative contributions of geographical differences on PCOS phenotypes. These findings may provide the basis for the development of strategies and best practices toward a standardized definition of PCOM and a more accurate ultrasonographic evaluation of PCOS.

Obesity is associated with alterations in antral follicle dynamics in eumenorrheic women.

STUDY QUESTION: Are ovarian antral follicle dynamics altered in women with obesity and regular ovulatory cycles? SUMMARY ANSWER: Eumenorrheic women with obesity display evidence of suppressed antral follicle dynamics as judged by fewer recruitment events, selectable follicles, and anovulatory dominant follicles, as well as lower anti-Müllerian hormone (AMH) concentrations and an increased prevalence of luteal phase defects. WHAT IS KNOWN ALREADY: Ovarian antral follicle development is a dynamic process involving distinct follicular and endocrine events that are critical for the occurrence of regular monthly ovulations. Follicle dynamics have not been prospectively evaluated in eumenorrheic women with obesity despite the known impact of obesity on gonadotropin production, ovarian steroid hormone concentrations, and fecundity. STUDY DESIGN, SIZE, DURATION: This was a prospective, longitudinal study of 42 women conducted over one inter-ovulatory interval (IOI). PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 21 women with obesity (total percent body fat ≥35%) and a group of 21 women without obesity (total percent body fat <35%) underwent transvaginal ultrasonography and venipuncture every-other-day for one IOI at an academic clinical research unit. Participants were aged 19-38 years and had a history of self-reported regular menstrual cycles (21-35 days). Follicle number and diameter (≥2 mm) were quantified at each visit. Individual growth profiles for all follicles that grew to ≥7 mm were assessed. Blood samples were assayed for gonadotropins, AMH, estradiol, and progesterone. MAIN RESULTS AND THE ROLE OF CHANCE: Women with obesity exhibited fewer recruitment events (mean ± SD, 1 ± 1 vs 2 ± 1 events; P = 0.010) and fewer selectable follicles (4 ± 3 vs 8 ± 6 follicles per participant; P = 0.022) during an IOI compared to women without obesity. AMH levels were lower in women with obesity (4.40 ± 3.01 vs 5.94 ± 2.49 ng/ml; P = 0.023), while gonadotropin profiles were similar between groups, across the IOI. Of the individual follicles tracked, fewer follicles progressed to >10 mm in the cohort with obesity (30 vs 40 follicles; P = 0.04) and fewer anovulatory follicles achieved dominance (9 vs 18 follicles; P = 0.041). Ovulatory follicles were selected at smaller diameters in women with compared to those without obesity (7.5 ± 1.6 vs 9.5 ± 1.9 mm; P = 0.001). Luteal phase defects were also more common in women with compared to those without obesity, as defined by either integrated (76 vs 29%, P = 0.002) or maximum (71 vs 24%, P = 0.002) luteal progesterone. LIMITATIONS, REASONS FOR CAUTION: This study was limited to an assessment of antral follicle dynamics and cannot inform on earlier stages of folliculogenesis. This study was observational and cannot address causation between obesity and altered antral follicle dynamics. Lastly, the data cannot be extrapolated to account for reduced fecundity and fertility in obesity. WIDER IMPLICATIONS OF THE FINDINGS: The increasing global prevalence of obesity necessitates an understanding of the mechanisms that underlie obesity-related adverse reproductive health outcomes. Eumenorrheic women with obesity demonstrate altered ovarian antral follicle and endocrine dynamics compared to their counterparts without obesity. The degree to which abnormal granulosa cell assembly and/or activity underlie the suboptimal luteinization and subfertility requires further investigation. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by Cornell University, President's Council of Cornell Women, United States Department of Agriculture (grant no. 8106), and National Institutes of Health (R01-HD0937848). B.Y.J. and H.V.B. were supported by doctoral training awards from the National Institutes of Health (T32-DK007158) and Canadian Institutes of Health Research (grant no. 146182), respectively. TRIAL REGISTRATION NUMBER: NCT01927432, NCT01785719.

Comparison of dietary and physical activity behaviors in women with and without polycystic ovary syndrome: a systematic review and meta-analysis of 39 471 women.

BACKGROUND: Lifestyle (dietary and/or physical activity [PA]) modification is recommended as first-line therapy to manage polycystic ovary syndrome (PCOS). Current recommendations are based on healthy lifestyle practices for the general public since evidence for unique lifestyle approaches in PCOS is limited and low quality. OBJECTIVE AND RATIONALE: We aimed to synthesize evidence on dietary and PA behaviors between women with PCOS and those without PCOS. Primary outcomes were overall diet quality, total energy intake and total PA, and secondary outcomes included macronutrients, micronutrients, food groups, foods, glycemic indices, sedentary time and sitting levels. We conducted this work to identify any unique lifestyle behaviors in women with PCOS that could underlie the propensity of weight gain and obesity in PCOS and be targeted for precision nutrition and PA interventions. These findings could be used to inform future practice recommendations and research that more effectively address complications (weight gain, obesity, diabetes, infertility, cardiovascular disease and mental health) in this high-risk population. SEARCH METHODS: Databases of MEDLINE, Web of Science, Scopus and CINAHL were searched until 15 February 2022 to identify observational studies documenting dietary and PA behaviors between women with PCOS and without PCOS (Controls). Studies on children, adolescents (<18 years), pregnant or menopausal-aged women (>50 years) were excluded. Data were pooled by random-effects models and expressed as (standardized) mean differences (MD) and 95% CIs. The risk of bias was assessed by the Newcastle-Ottawa scale (NOS). OUTCOMES: Fifty-four studies (N = 39 471 participants; [n = 8736 PCOS; 30 735 Controls]) were eligible (96%; [52/54] NOS scores ≥ 7). Women with PCOS had higher cholesterol (MD: 12.78, 95% CI: 1.48 to 24.08 mg/day; P = 0.03; I2 = 19%), lower magnesium (MD: -21.46, 95% CI: -41.03 to -1.91 mg/day; P = 0.03; I2 = 76%), and a tendency for lower zinc (MD: -1.08, 95% CI: -2.19 to -0.03 mg/day; P = 0.05; I2 = 96%) intake, despite lower alcohol consumption (MD: -0.95, 95% CI: -1.67 to 0.22 g/day; P = 0.02; I2 = 0%) versus Controls. Also, women with PCOS had lower total PA (standardized mean difference: -0.38, 95% CI: -0.72 to 0.03; P = 0.03; I2 = 98%). Conversely, energy, macronutrients (carbohydrate, fat, protein, fiber), micronutrients (folic acid, iron, calcium, sodium), glycemic index and glycemic load were similar (all: P ≥ 0.06). Most eligible studies reported lower total adherence to healthy eating patterns or poorer consumption of major food groups (grains, fruits, vegetables, proteins, seeds, nuts, dairy) in women with PCOS, as described narratively since variable study methodology did not permit meta-analyses. WIDER IMPLICATIONS: Collective evidence supports that women with PCOS have a lower overall diet quality, poorer dietary intakes (higher cholesterol, lower magnesium and zinc) and lower total PA, despite lower alcohol consumption versus those without PCOS. Considerable heterogeneity among studies reinforces the need for research to address any relative contributions of other factors (e.g. genetic, metabolic or sociodemographic) to the observed differences. These clarifications may contribute to future evidence-based guideline recommendations on monitoring and managing PCOS in the era of precision lifestyle medicine.

Challenges in diagnosis and understanding of natural history of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting 8%-13% of reproductive-aged women. The aetiology of the syndrome is complex, with genetic susceptibility, androgen exposure in early life and adiposity related dysfunction leading to perturbance in hypothalamic-ovarian function. PCOS clinical features are heterogeneous, with manifestations arising even in early adolescence, developing into multisystem reproductive, metabolic and psychological manifestations in adulthood. In this review, we will discuss challenges in the diagnosis of PCOS and understanding of the natural history of PCOS.

Comprehensive evaluation of disparities in cardiometabolic and reproductive risk between Hispanic and White women with polycystic ovary syndrome in the United States: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to comprehensively compare cardiometabolic and reproductive health risk between Hispanic and White women with polycystic ovary syndrome in the United States in response to the call by the international guideline for polycystic ovary syndrome to delineate health disparities. DATA SOURCES: Databases of MEDLINE, Web of Science, and Scopus were initially searched through October 25, 2020, and confirmed on February 1, 2021. STUDY ELIGIBILITY CRITERIA: Observational studies comparing glucoregulatory, lipid profile, anthropometric, blood pressure, androgen, ovarian morphology, oligoanovulation, and infertility status between Hispanic and White women with polycystic ovary syndrome were included. The primary outcome was metabolic syndrome risk. Furthermore, major cardiovascular events (stroke, coronary heart disease, and heart failure) and mortality rate (cardiovascular death and total mortality) data were evaluated. Studies on adolescents (<2 years after menarche), pregnant, or menopausal-aged women (>50 years) were excluded. METHODS: Data were pooled by random-effects models and expressed as mean differences and 95% confidence intervals. Risk of bias was assessed by the Newcastle-Ottawa Scale. RESULTS: A total of 11 studies (n=2267; 589 Hispanic and 1678 White women) were eligible. All studies, including both White and Hispanic women, had high-quality assessment (Newcastle-Ottawa Scale score of ≥8). Hispanic women exhibited comparable metabolic syndrome prevalence (7% [95% confidence interval, -1 to 14]; P=.06; I2=0%); however, Hispanic women exhibited higher modified Ferriman-Gallwey score (0.60 [95% confidence interval, -0.01 to 1.21]; P=.05; I2=0%), fasting insulin (5.48 µIU/mL [95% confidence interval, 3.11-7.85]; P≤.01; I2=40.0%), and homeostatic model assessment of insulin resistance (1.20 [95% confidence interval, 0.50-1.89]; P≤.01; I2=43.0%) than White women. The 2 groups had comparable glucose, lipid profile, waist circumference, blood pressure, and androgen status (all P≥.08). Findings about group differences in certain reproductive outcomes (ie, ovarian dysmorphology and infertility) were contradictory and described only narratively as inclusion in the meta-analyses was not possible. No study reported on cardiovascular events or mortality. CONCLUSION: Hispanic women with polycystic ovary syndrome exhibited greater impairments in glucoregulatory status than White women. Disparities in reproductive risks could not be concluded. The degree to which glucoregulatory aberrations translate into patient-pressing diseases (diabetes mellitus and infertility) remains a major roadblock given the paucity of available evidence. Our observations have supported the consideration of these disparities in the diagnostic, monitoring, and management practices for polycystic ovary syndrome and reinforced the need to elucidate mechanisms that account for the observed disparities to foster equity in polycystic ovary syndrome care.

A comparison of two- and three-dimensional ultrasonographic methods for evaluation of ovarian follicle counts and classification of polycystic ovarian morphology.

OBJECTIVES: To determine the level of agreement across assessments of follicle number per ovary (FNPO) and classifying of polycystic ovarian morphology (PCOM; FNPO ≥25) with the use of various real-time (RT) and off-line two-dimensional (2D) and three-dimensional (3D) ultrasonographic methods. DESIGN: Method comparison study. SETTING: University-based clinical research unit. PATIENT(S): Sixteen women with and without PCOM. INTERVENTION: Thirty-two ovaries were analyzed with the use of eight ultrasonographic methods: 2D-Grid (reference method), 2D-RT, 2D-RT with Grid, multiplanar view (MPV), MPV-RT, tomographic ultrasound imaging (TUI), TUI-RT, and semiautomated volume calculation (SonoAVC). MAIN OUTCOME MEASURE(S): FNPO, PCOM status, and time to obtain FNPO. Clinical feasibility, defined as the time taken to obtain FNPO, also was evaluated. RESULT(S): 2D-RT overestimated FNPO versus 2D-Grid (3 ± 9 follicles) owing to overcounting in non-PCOM ovaries (6 ± 6 follicles). However, systematic bias was not detected when a grid overlay was incorporated (2D-RT with Grid). SonoAVC underestimated FNPO (-3 ± 5 follicles), particularly in PCOM ovaries (-4.1 ± 5.0 follicles). No bias in FNPO was detected between MPV, TUI, or TUI-RT versus 2D-Grid. 2D-RT significantly misclassified ovaries as PCOM. All methods except MPV took less time to complete FNPO assessments compared with 2D-Grid. CONCLUSION(S): Variability in FNPO across ultrasonographic methods limits their interchangeable use, particularly when a precise metric is needed. 2D-RT may be problematic owing to its propensity to misclassify PCOM. 2D-RT with Grid and MPV-RT could represent clinically feasible alternatives to obtain FNPO and classify PCOM. Efforts to reduce variation in FNPO will clarify the relevance of PCOM in women's health.

Associations of diet, physical activity and polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults Women's Study.

BACKGROUND: Current evidence supports the adoption of healthy diet and physical activity (PA) behaviors in patients with polycystic ovary syndrome (PCOS), given the positive effects of those behaviors on physical well-being. An improved understanding of the associations between diet and PA with PCOS is needed to ascertain whether tailored dietary and PA recommendations are needed for this population. Thus, we investigated the associations of diet and PA with PCOS and its isolated features. METHODS: Cross-sectional study. Of the 748 women who were included in this study from the Coronary Artery Risk Development in Young Adults (CARDIA) Women's Study, 40 were classified as having PCOS, 104 had isolated hyperandrogenism (HA) and 75 had isolated oligomenorrhea (OA). Dietary intake was measured using the CARDIA diet history questionnaire and diet quality was scored using the Alternative Healthy Eating Index 2010; a higher score indicated a better quality diet. Self-reported PA was measured using a validated interviewer-administered questionnaire. Polytomous logistic regression analyses examined the associations between diet and PA with PCOS, HA, and OA status (outcomes), adjusting for age, race, total energy intake, education, and/or body mass index. The threshold for statistical significance was set at p < 0.05. RESULTS: Mean age of the participants was 25.4 years (SD 3.6) and 46.8% of participants were Black women. There was little to no association of total energy intake, nutrients, diet quality, and PA with PCOS, HA or OA status. CONCLUSION: Energy intake, nutrient composition, diet quality, and PA were not associated with PCOS, supporting recent PCOS guidelines of using national recommendations for the general population to encourage health-promoting behaviors among women with PCOS. However, longitudinal studies evaluating changes in diet and physical activity in relation to the development and/or the progression of PCOS are needed to establish a causal association.

Disparities in cardio metabolic risk between Black and White women with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to summarize and quantitatively pool evidence on cardiometabolic health disparities between Black and White women with polycystic ovary syndrome in the United States in response to the call for further delineation of these disparities in the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. DATA SOURCES: Databases of MEDLINE, Web of Science, and Scopus were searched initially through March 05, 2020, and confirmed on September 11, 2020. STUDY ELIGIBILITY CRITERIA: Observational studies documenting cardiometabolic risk profile (glucoregulatory, lipid profile, anthropometric, and blood pressure status) in Black and White women with polycystic ovary syndrome were included. Studies on children (<17 years old) and pregnant or menopausal-aged women (>50 years) were excluded. The primary outcome was fasting glucose. Furthermore, data on major cardiovascular events (stroke, coronary heart disease, heart failure) and mortality rate (cardiovascular death, total mortality) were evaluated. METHODS: Data were pooled by random-effects models and expressed as mean differences and 95% confidence intervals. Studies were weighted based on the inverse of the variance. Heterogeneity was evaluated by Cochran Q and I2 statistics. Study methodologic quality was assessed by the Newcastle-Ottawa scale. RESULTS: A total of 11 studies (N=2851 [652 Black and 2199 White]) evaluated cardiometabolic risk profile and all had high quality (Newcastle-Ottawa scale score of ≥8). No studies reported on cardiovascular events and mortality rate. Black women had comparable fasting glucose (-0.61 [-1.69 to 2.92] mg/dL; I2=62.5%), yet exhibited increased fasting insulin (6.76 [4.97-8.56] µIU/mL; I2=59.0%); homeostatic model assessment of insulin resistance (1.47 [0.86-2.08]; I2=83.2%); systolic blood pressure (3.32 [0.34-6.30] mm Hg; I2=52.0%); and decreased triglyceride (-32.56 [-54.69 to -10.42] mg/dL; I2=68.0%) compared with White women (all, P≤.03). Groups exhibited comparable total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and diastolic blood pressure (all, P≥.06). CONCLUSIONS: Black women with polycystic ovary syndrome have a greater tendency for an adverse cardiometabolic risk profile (increased insulin, homeostatic model assessment of insulin resistance, and systolic blood pressure) despite lower triglycerides than White women. Our observations support the consideration of these disparities for diagnostic, monitoring, and management practices in Black women and for future guideline recommendations. Given the heterogeneity among studies, future research should address the relative contributions of biologic, environmental, socioeconomic, and healthcare factors to the observed disparities. Furthermore, longitudinal research is required to address patient-pressing complications, including cardiovascular events and mortality rate in Black women with polycystic ovary syndrome as a high-risk yet understudied population.

Polycystic Ovary Syndrome and Incidental Diagnosis of Mosaic Turner Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. Mosaic Turner syndrome (TS) is a genetic disorder with significant phenotypic variability. The occurrence of PCOS in women with mosaic TS has been infrequently studied. CASE: A 30-year-old nulligravid woman presented with oligomenorrhea, hyperandrogenism, infertility, and ultrasound polycystic ovary morphology. She was diagnosed with PCOS and conceived following ovulation induction. After 2 inconclusive non-invasive prenatal screening results, she was referred to medical genetics. A maternal karyotype resulted in a diagnosis of 45,X/46,XX mosaic TS. She delivered a healthy 46,XY infant at term. CONCLUSION: PCOS can affect women with mosaic TS. Further studies are needed to better characterize the reproductive profile of women with mosaic TS, including the presentation of concurrent PCOS.

Effects of Dietary Glycemic Index and Glycemic Load on Cardiometabolic and Reproductive Profiles in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Women with polycystic ovary syndrome (PCOS) exhibit cardiometabolic (e.g., insulin resistance) and associated reproductive disruptions. Lifestyle modification (e.g., diet) is recommended as the first-line therapy to manage PCOS; however, a favorable dietary regimen remains unclear beyond energy restriction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to summarize evidence on impacts of dietary glycemic index (GI) or glycemic load (GL) on cardiometabolic and reproductive profiles to update the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Cochrane, Web of Science, and Scopus were searched through 30 October 2019, and confirmed on 25 March 2020, to identify RCTs (≥8 wk) comparing the effects of diets with lower (LGI/LGL) and higher (HGI/HGL) GI/GL on glucoregulatory outcomes, lipid profile, anthropometrics, and androgen status in PCOS. The primary outcome was HOMA-IR. Data were pooled by random-effects models and expressed as weighted mean differences and 95% CIs. The risk of bias was assessed by the Cochrane tool. Ten RCTs (n = 403) were eligible. Eight evaluated LGI and 2 LGL diets. LGI diets decreased HOMA-IR (-0.78; -1.20, -0.37; I2 = 86.6%), fasting insulin (-2.39; -4.78, 0.00 µIU/mL; I2 = 76.8%), total cholesterol (-11.13; -18.23, -4.04 mg/dL; I2 = 0.0%), LDL cholesterol (-6.27; -12.01, -0.53 mg/dL; I2 = 0.0%), triglycerides (-14.85; -28.75, -0.95 mg/dL; I2 = 31.0%), waist circumference (-2.81; -4.40, -1.23 cm; I2 = 53.9%), and total testosterone (-0.21; -0.32, -0.09 nmol/L; I2 = 8.6%) compared with HGI diets (all: P ≤ 0.05) without affecting fasting glucose, HDL cholesterol, weight, or free androgen index (all: P ≥ 0.07). Some results were contradictory and only described narratively for 2 RCTs that evaluated LGL diets, since inclusion in meta-analyses was not possible. LGI diets improved glucoregulatory outcomes (HOMA-IR, insulin), lipid profiles, abdominal adiposity, and androgen status, conceivably supporting their inclusion for dietary management of PCOS. Further RCTs should confirm these observations and address whether LGI diets improve more patient-pressing complications, including ovulatory cyclicity, infertility, and cardiovascular disease risk in this high-risk population. This review was registered at www.crd.york.ac.uk/PROSPERO as CRD42020175300.

Ultrasound Characterization of Disordered Antral Follicle Development in Women with Polycystic Ovary Syndrome.

CONTEXT: The mechanism of oligo-anovulation in polycystic ovary syndrome (PCOS) is unknown. OBJECTIVES: To evaluate follicular and endocrine characteristics of anovulatory and sporadic ovulatory cycles in women with PCOS. DESIGN: Prospective, longitudinal study. SETTING: Academic clinical research unit. PARTICIPANTS: 26 reproductive-aged women (18-38 years) with PCOS, observed during natural anovulatory (PCOS-Anov; n = 12) and sporadic ovulatory cycles (PCOS-Ov; n = 14), and 12 controls. INTERVENTIONS: Transvaginal ultrasonography and venipuncture were performed every other day for 4 to 6 weeks in women with PCOS or at 1 interovulatory interval in control subjects. MAIN OUTCOME MEASURES: Follicle number and diameter (ie, ≥2 mm) were quantified at each visit. Individual growth profiles were assessed for all follicles that grew to ≥7 mm. Blood samples were assayed for follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone. RESULTS: Follicular excess, or heightened follicle number versus controls, was observed across anovulatory and sporadic ovulatory cycles in PCOS. In PCOS-Anov, follicles emerged cyclically in some women (6/12; 50%) and continuously in others (6/12; 50%), then grew to a mean maximum diameter of 7.2 mm and regressed within 4.7 days. In PCOS-Ov, follicles mostly emerged cyclically as part of a cohort and dominant follicles showed normal growth to ovulation-albeit mean and maximum luteal progesterone concentrations were significantly lower versus controls. CONCLUSIONS: Follicle growth and regression were detected on ultrasonography amidst perpetual follicular excess in PCOS. Documentation of continuous follicle recruitment and turnover, the absence of persistence, and altered luteal progesterone following sporadic ovulation, provide formative data on antral follicle development in PCOS.

Osteosarcopenia in Reproductive-Aged Women with Polycystic Ovary Syndrome: A Multicenter Case-Control Study.

CONTEXT: Osteosarcopenia (loss of skeletal muscle and bone mass and/or function usually associated with aging) shares pathophysiological mechanisms with polycystic ovary syndrome (PCOS). However, the relationship between osteosarcopenia and PCOS remains unclear. OBJECTIVE: We evaluated skeletal muscle index% (SMI% = [appendicular muscle mass/weight (kg)] × 100) and bone mineral density (BMD) in PCOS (hyperandrogenism + oligoamenorrhea), and contrasted these musculoskeletal markers against 3 reproductive phenotypes (i): HA (hyperandrogenism + eumenorrhea) (ii); OA (normoandrogenic + oligoamenorrhea) and (iii), controls (normoandrogenic + eumenorrhea). Endocrine predictors of SMI% and BMD were evaluated across the groups. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control study of 203 women (18-48 years old) in New York State. RESULTS: PCOS group exhibited reduced SMI% (mean [95% confidence interval (CI)]; 26.2% [25.1,27.3] vs 28.8% [27.7,29.8]), lower-extremity SMI% (57.6% [56.7,60.0] vs 62.5% [60.3,64.6]), and BMD (1.11 [1.08,1.14] vs 1.17 [1.14,1.20] g/cm2) compared to controls. PCOS group also had decreased upper (0.72 [0.70,0.74] vs 0.77 [0.75,0.79] g/cm2) and lower (1.13 [1.10,1.16] vs 1.19 [1.16,1.22] g/cm2) limb BMD compared to HA. Matsuda index was lower in PCOS vs controls and positively associated with SMI% in all groups (all Ps ≤ 0.05). Only controls showed associations between insulin-like growth factor (IGF) 1 and upper (r = 0.84) and lower (r = 0.72) limb BMD (all Ps < 0.01). Unlike in PCOS, IGF-binding protein 2 was associated with SMI% in controls (r = 0.45) and HA (r = 0.67), and with upper limb BMD (r = 0.98) in HA (all Ps < 0.05). CONCLUSIONS: Women with PCOS exhibit early signs of osteosarcopenia when compared to controls likely attributed to disrupted insulin function. Understanding the degree of musculoskeletal deterioration in PCOS is critical for implementing targeted interventions that prevent and delay osteosarcopenia in this clinical population.

Dietary and Physical Activity Behaviors in Women with Polycystic Ovary Syndrome per the New International Evidence-Based Guideline.

Lifestyle modifications are recommended as first-line therapy in polycystic ovary syndrome (PCOS). However, usual dietary and physical activity (PA) behaviors of women with PCOS remain uncertain, likely owing to controversy in diagnostic criteria. Our objective was to contrast the usual dietary and PA behaviors of women with PCOS (n = 80) diagnosed by the 2018 International Evidence-based Guideline for the Assessment and Management of PCOS to that of controls (n = 44). Study outcomes were dietary intake, diet quality (Healthy Eating Index-2015), and PA (questionnaire, waist-worn accelerometers). Women with PCOS met the acceptable macronutrient distribution ranges for carbohydrate, fat, and protein, but did not meet the recommended dietary reference intakes for vitamin D (mean (95% confidence interval); 6 (5-7) µg/d), vitamin B9 (275 (252-298) µg/d), total fiber (24 (22-26) g/d), or sodium (4.0 (3.6-4.4) g/d). Women with PCOS also met the US recommendations for PA. No differences were detected in dietary intake, diet quality, or PA levels between groups (p ≥ 0.11). In conclusion, women with and without PCOS have comparable dietary and PA behaviors. A lack of unique targets for dietary or PA interventions supports the position of the new guideline to foster healthy lifestyle recommendations for the management of PCOS.

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.

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.

Ovarian Morphology by Transabdominal Ultrasound Correlates With Reproductive and Metabolic Disturbance in Adolescents With PCOS.

PURPOSE: To determine whether ovarian morphology imaged using transabdominal ultrasonography reflects clinical and metabolic features in adolescents with polycystic ovary syndrome (PCOS). METHODS: A retrospective pilot study was conducted in 33 adolescents (12-18 years) with PCOS as defined by hyperandrogenism and irregular cycles. Adolescents underwent the following assessments at a random time during the menstrual cycle: transabdominal ultrasonography, physical examination (height, weight, and systolic and diastolic blood pressure), fasting hormonal tests (free, percent free, and total testosterone, androstenedione, follicle stimulating hormone, luteinizing hormone), and metabolic tests (including an oral glucose tolerance test, fasting and 2-hour insulin and glucose, homeostatic model assessment of insulin resistance, and whole-body insulin sensitivity index). Ultrasound images were analyzed offline for ovarian area (OA), ovarian volume (OV), follicle number per cross section (FNPS), and follicle distribution pattern. Associations among endocrine and metabolic variables with sonographic features were assessed by Spearman's rank correlation coefficients and stepwise multiple linear regression. RESULTS: Total testosterone and androstenedione, but not free testosterone, or percent free testosterone, positively correlated with OA (ρ = .515, ρ = .422, respectively), OV (ρ = .451, ρ = .382), and FNPS (ρ = .394, ρ = .474). Luteinizing hormone:follicle stimulating hormone ratio also positively correlated with ovarian size (OA, ρ = .520 and OV, ρ = .409). Unexpectedly, body mass index (ρ = -.503) and fasting glucose levels (ρ = -.393) were inversely correlated with FNPS. Total testosterone was an independent predictor of FNPS, OA, and OV as judged by stepwise multiple regression analyses. CONCLUSIONS: Some aspects of ovarian morphology in adolescents with PCOS using transabdominal ultrasonography associate with markers of reproductive dysfunction and provide rationale to further investigate how ovarian morphology may reflect concurrent metabolic dysfunction.

Health-related knowledge, beliefs and self-efficacy in women with polycystic ovary syndrome.

STUDY QUESTION: Do health-related knowledge, beliefs and self-efficacy differ between women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Women with PCOS felt at greater risk for adverse health outcomes, yet believed a healthy lifestyle was less beneficial to prevent weight gain relative to a comparison group. WHAT IS KNOWN ALREADY: Diet and physical activity are often used to treat PCOS, but there are high attrition rates and less engagement in self-help methods. It is unclear whether there are unique psychosocial considerations in PCOS that should be incorporated into these interventions. STUDY DESIGN, SIZE, DURATION: This cross-sectional study enrolled 475 women with (N = 255) and without PCOS (N = 220). PARTICIPANTS/MATERIALS, SETTING, METHODS: Female participants were recruited through paper and web-based advertisements across the US (mean age: 28.1 ± 5.4 years). Participants were either diagnosed with PCOS by a healthcare professional (PCOS group) or had self-reported regular menstrual cycles (comparison group). A reliable and valid online instrument about health-related knowledge, beliefs and self-efficacy was administered to these participants. MAIN RESULTS AND THE ROLE OF CHANCE: Most women with PCOS had a basic understanding of nutrition (96%), but had misconceptions about diagnostic criteria for PCOS (≥86%). PCOS was associated with greater perceived susceptibility for disease and weight gain and poorer perceived control over these health outcomes (all P < 0.05), in relation to the comparison group. Women with PCOS also perceived fewer benefits of healthy behaviors on weight gain (P = 0.03) with less than half of the PCOS group attempting to follow government diet recommendations (47%). There were no differences in the self-efficacy of dietary behaviors between groups. LIMITATIONS, REASONS FOR CAUTION: It is likely that participant self-selection occurred due to the nature of recruitment in this study and results may have limited generalizability since most participants identified as Caucasian. Additionally, it is unclear whether some results may be clinically meaningful due to small effect sizes. WIDER IMPLICATIONS OF THE FINDINGS: These findings support that behavioral interventions should incorporate the unique psychosocial considerations associated with PCOS to encourage patient participation in lifestyle interventions. STUDY FUNDING/COMPETING INTEREST(S): This manuscript was partially supported by Cornell University Human Ecology Alumni Association and College of Agriculture and Life Sciences Alumni Association. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NCT01859663.