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.

Overnight Melatonin Concentration and Sleep Quality Are Associated with the Clinical Features of Polycystic Ovary Syndrome.

Circulating melatonin is elevated in women with polycystic ovary syndrome (PCOS); whether circadian disruptions coincide with sleep disturbances in women with PCOS or their symptom severity is unclear. The objective of this observational pilot study was to determine whether altered patterns of melatonin excretion are associated with reduced sleep quality in women with versus without PCOS. Participants underwent a clinical assessment, transvaginal ultrasound, and reproductive hormone testing. Morning and evening urine samples were assayed for urinary 6-sulfatoxymelatonin (MEL) as a proxy for melatonin production. The night (morning MEL)-to-day (evening MEL) ratio, or N:D ratio, was determined to approximate the rhythm of MEL production. Sleep quality and duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy. No differences were detected in overnight MEL, daytime MEL, or the N:D ratio in participants with PCOS versus controls. The PCOS group experienced reduced weekend sleep efficiency vs. controls (81% vs. 88% p < 0.05). The number of follicles per ovary (FNPO) was positively associated with overnight MEL (r = 0.359, p < 0.05). Weekend sleep time and overnight MEL concentrations were dependent on PCOS status. Therefore, diagnostic features of PCOS were associated with MEL production and sleep disturbances, suggesting that women with a more severe clinical presentation of PCOS may be more likely to experience altered MEL production or sleep disturbances.

Diagnostic Performance of Ovarian Morphology on Ultrasonography across Anovulatory Conditions-Impact of Body Mass Index.

The study objectives were to determine whether ovarian morphology can distinguish between women with regular menstrual cycles, normo-androgenic anovulation (NA-Anov), and PCOS and whether body mass index (BMI)-specific thresholds improved diagnostic potential. Women with PCOS (biochemical and/or clinical hyperandrogenism and irregular cycles; N = 66), NA-Anov (irregular cycles without clinical and/or biochemical hyperandrogenism; N = 64), or regular cycles (controls; cycles every 21-35 days in the absence of clinical or biochemical hyperandrogenism; N = 51) were evaluated. Participants underwent a reproductive history, physical exam, transvaginal ultrasound, and a fasting blood sample. Linear regression analyses were used to assess the impact of BMI on ovarian morphology across groups. The diagnostic performance of ovarian morphology for anovulatory conditions, and by BMI (lean: <25 kg/m2; overweight: ≥25 kg/m2), was tested using Receiver Operating Characteristic (ROC) curves. Follicle number per ovary (FNPO) and ovarian volume (OV), but not follicle number per cross-section (FNPS), increased across controls, NA-Anov, and PCOS. Overall, FNPO had the best diagnostic performance for PCOS versus controls (AUCROC = 0.815) and NA-Anov and controls (AUCROC = 0.704), and OV to differentiate between PCOS and NA-Anov (AUCROC = 0.698). In lean women, FNPO best differentiated between PCOS and controls (AUCROC = 0.843) and PCOS versus NA-Anov (AUCROC = 0.710). FNPS better distinguished between NA-Anov and controls (AUCROC = 0.687), although diagnostic performance was lower than when thresholds were generated using all participants. In women with overweight and obesity, OV persisted as the best diagnostic feature across all analyses (PCOS versus control, AUCROC = 0.885; PCOS versus NA-Anov, AUCROC = 0.673; NA-Anov versus controls, AUCROC = 0.754). Ovarian morphology holds diagnostic potential to distinguish between NA-Anov and PCOS, with marginal differences in diagnostic potential when participants were stratified by BMI suggesting that follicle number may provide better diagnostic performance in lean women and ovarian size in those with overweight.

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.

Reliability and Agreement of Ultrasonographic Measures of the Ovarian Stroma: Impact of Methodology.

OBJECTIVES: Increased ovarian stromal area (SA), stromal-to-ovarian area ratio (S/A), and echogenicity (SEcho) on ultrasonography have been proposed as diagnostic markers for polycystic ovary syndrome. Although several methods to evaluate the stroma exist, their reproducibility has not been defined which limits clinical utility. This study aimed to determine the interrater reliability and agreement of methods to evaluate SA, S/A, and SEcho. METHODS: Five raters tested 3 methods to obtain SA and S/A, and one to obtain SEcho on 30 ovarian cineloops under two imaging conditions, simulating real-time (free-choice) or offline (fixed-frame) imaging. For SA, Method 1 subtracted follicular area from the ovarian area, Method 2 involved outlining the periphery of the stroma, and Method 3 represented a hybrid approach in which central follicles were subtracted from the outlined stroma. SEcho was scored on a subjective 3-tiered scale. Intraclass correlation coefficients (ICCs) and the coefficient of variation were determined for SA and S/A, and Fleiss' kappa agreement statistics (κ) were determined for SEcho. RESULTS: Interrater reliability of SA was superior using Method 1 (ICC = 0.558 and ICC = 0.705) versus Method 2 (ICC = 0.522 and ICC = 0.230) or Method 3 (ICC = 0.429 and ICC = 0.305) under free-choice and fixed-frame imaging conditions, respectively. Interrater reliability of S/A was also moderate to poor across methods. SEcho was also not reliably assessed across raters (κ = <0.500). CONCLUSIONS: Ultrasonographic assessments of the ovarian stroma were associated with moderate to poor reproducibility. Indirect estimates of the ovarian stroma (Method 1) could be optimized to yield a reproducible approach, clarifying the clinical relevance of the stroma.

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.

Obesity, Insulin Resistance, and Hyperandrogenism Mediate the Link between Poor Diet Quality and Ovarian Dysmorphology in Reproductive-Aged Women.

The relationship between diet quality and ovarian morphology has biological plausibility yet remains unclear and was therefore evaluated. In a multicenter cross-sectional analysis, four dietary patterns were scored for 111 consecutive reproductive-aged women (18-45 years) using (1) Healthy Eating Index (HEI-2015); (2) alternative HEI-2010; (3) alternate Mediterranean Diet (aMED); (4) and Dietary Approaches to Stop Hypertension (DASH) indices. Ovarian volume (OV) and follicle number per ovary (FNPO) were evaluated on transvaginal ultrasonography. Relationships between dietary and ovarian morphology indices were evaluated by linear regression and mediation analyses. Associations between aMED and DASH scores and OV/FNPO were completely mediated by obesity, insulin resistance, and hyperandrogenism (All: p < 0.05), unlike direct associations (All: p ≥ 0.89). Namely, a 1-standard deviation [SD] increase in aMED score was associated with decreases in OV (0.09 SD; 0.4 mL) through reducing waist circumference. Likewise, a 1 SD increase in aMED and DASH score was associated with decreases in OV (0.07 SD; 0.3 mL) by reducing glucose response to a 75 g glucose tolerance test. A 1 SD increase in DASH score was associated with decreased FNPO (0.07 SD; 2 follicles) by reducing free androgen index (All: p < 0.05). Adherence to aMED and DASH eating plans was indirectly associated with significant improvements in ovarian form, providing novel mechanistic insights for future interventions about contributions of diet quality on ovarian function.

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.

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.

Impact of hypocaloric dietary intervention on ovulation in obese women with PCOS.

Polycystic ovary syndrome (PCOS) is a common cause of ovulatory dysfunction impacting women of reproductive age. Obesity and insulin resistance are thought to potentiate disruptions in antral follicle development that result in chronic anovulation, and as such, have become important therapeutic targets of dietary interventions aimed at weight loss. Caloric restriction has been shown to promote sporadic ovulation in obese women with PCOS, but improvements have occurred across a wide range of patients and little has been garnered about the factors that distinguish responders from non-responders. Further, few studies have evaluated the likelihood for modest weight loss to restore normal ovulatory cyclicity in PCOS. Consensus regarding the impact of dietary intervention on ovulation has been limited by variability in the measures used to characterize and report ovulatory status across studies. In response, this review provides an assessment of the evidence surrounding the effectiveness of hypocaloric dietary intervention to normalize ovulatory function in PCOS. The impact of physiological versus methodological factors on the evaluation of ovulatory status is discussed and recommendations to strengthen future studies in this area are provided. Ultimately, further research is needed to understand the optimal dietary or lifestyle approaches that promote ovulation and sustained improvements in reproductive function in PCOS.

Sonographic markers of ovarian morphology, but not hirsutism indices, predict serum total testosterone in women with regular menstrual cycles.

OBJECTIVE: To determine whether sonographic markers of ovarian morphology or male pattern hair growth scores predict androgen levels in women with regular or irregular menstrual cycles. DESIGN: Cross-sectional observational study. SETTING: Clinical research unit. PATIENT(S): Seventy-six women of reproductive age (18-39 years) were evaluated for male-pattern hair growth (using a modified Ferriman-Gallwey scoring system), ovarian morphology (by transvaginal ultrasonography), and total serum testosterone (T) (by liquid chromatography tandem mass spectrometry). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Regional and total modified Ferriman-Gallwey scores, number of follicles per follicle size category, follicle number per ovary, ovarian volume, ovarian area, stromal to ovarian area ratio, stromal echogenicity index, total testosterone (total T), and menstrual cycle length. RESULT(S): Neither regional nor total modified Ferriman-Gallwey scores correlated with total T concentrations in women with regular or irregular menstrual cycles, as judged by the Least Absolute Shrinkage and Selection Operator technique. By contrast, a sonographic marker (follicle number per ovary 6-9 mm) significantly predicted total T concentrations in women with regular menstrual cycles but not in women with irregular menstrual cycles. CONCLUSION(S): Sonographic markers of ovarian morphology, but not hirsutism scores, predicted total T levels. However, the predictive value of ovarian morphology for total T differed by menstrual cycle status. That sonographic markers did not predict androgen levels in a diverse cohort of women with cycle irregularity suggests the potential for distinct variations in ovarian morphology for androgenic and nonandrogenic types of cycle irregularity. Overall, our findings support that an assessment of ovarian morphology may be helpful in reflecting total T levels.

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.