Evaluating the diagnostic accuracy of androgen measurement in polycystic ovary syndrome: a systematic review and diagnostic meta-analysis to inform evidence-based guidelines.

BACKGROUND: Biochemical hyperandrogenism is a hallmark and diagnostic feature of polycystic ovary syndrome (PCOS). However, the most accurate androgen measurement for assessing biochemical hyperandrogenism in PCOS diagnosis remains uncertain. OBJECTIVE AND RATIONALE: This systematic review aimed to assess different androgen measures [including total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), and dihydrotestosterone (DHT)] for accuracy in diagnosing biochemical hyperandrogenism in women with PCOS, to inform the 2023 International PCOS Evidence-based Guidelines. SEARCH METHODS: To update evidence from the 2018 International PCOS Guidelines, a systematic search from 3 July 2017 to 23 June 2023 was conducted across Medline (Ovid), CINAHL, all EBM, EMBASE, and PsycInfo for articles evaluating androgens in the diagnosis of biochemical hyperandrogenism. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias and applicability. A diagnostic test accuracy meta-analysis was performed using STATA 18 software. Summary sensitivity and specificity were calculated with 95% CIs using the bivariate model, while the hierarchical summary receiver operating characteristics (ROC) model was used to produce a summary ROC curve. OUTCOMES: Of 23 studies reviewed, 18 were included in the meta-analysis, with data from 2857 participants (1650 with PCOS and 1207 controls). For diagnosing biochemical hyperandrogenism in PCOS, the pooled sensitivity, specificity, and AUC with 95% CI were for TT: 0.74 (0.63-0.82), 0.86 (0.77-0.91), and 0.87 (0.84-0.90); cFT: 0.89 (0.69-0.96), 0.83 (0.79-0.86), and 0.85 (0.81-0.88); FAI: 0.78 (0.70-0.83), 0.85 (0.76-0.90), and 0.87 (0.84-0.90); A4: 0.75 (0.60-0.86), 0.71 (0.51-0.85), and 0.80 (0.76-0.83); and DHEAS: 0.75 (0.61-0.85), 0.67 (0.48-0.81), and 0.77 (0.73-0.81), respectively. In subgroup analyses, liquid chromatography with tandem mass spectrometry (LC-MS/MS) had superior sensitivity for measuring cFT, FAI, A4, and DHEAS, and superior specificity for measuring TT, cFT, and FAI, compared to the direct immunoassay method. WIDER IMPLICATIONS: Our results directly informed the 2023 International PCOS Guideline recommendations to use TT and FT as the first-line laboratory tests to assess biochemical hyperandrogenism in the diagnosis of PCOS. cFT should be assessed by equilibrium dialysis or ammonium sulfate precipitation, or calculated using FAI. If TT or cFT are not elevated, A4 and DHEAS could also be considered, noting their poorer specificity. Laboratories should utilize LC-MS/MS for androgen measurement given its high accuracy. Future studies should focus on establishing optimal normative cut-off values in large, unselected, and ethnically diverse cohorts of women. REGISTRATION NUMBER: The review protocol was prepublished in the 2023 PCOS Guideline Technical Report (https://www.monash.edu/__data/assets/pdf_file/0010/3379591/TechnicalReport-2023.pdf).

How Frequently Is Ultrasound Required to Diagnose Polycystic Ovary Syndrome in a Clinical Population?

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting up to 20% of reproductive aged women worldwide. Polycystic ovarian morphology (PCOM) may be present, but is not required for diagnosis. Our study seeks to evaluate the utility of ultrasound in diagnosing or excluding PCOS by 2023 International Guidelines Criteria. Materials and Methods: Subjects were patients seen in a tertiary care referral clinic in whom other causes of hyperandrogenism (HA) were ruled out. All underwent complete history, physical, modified Ferriman Gallwey scoring, and serum androgen testing; followed by transvaginal ultrasound (TVUS) to assess ovarian morphology if indicated. PCOM was identified as antral follicle count ≥20 and/or ovarian volume >10 mL in at least one ovary. After clinical classification, PCOS was diagnosed by at least two of three: biochemical/clinical HA, ovulatory dysfunction (OD), and PCOM. Statistics were calculated using Fisher's exact test and chi-square. Results: In total, 454 subjects were included. 299 were classified as group A/B and did not require TVUS for diagnosis. Of 82 subjects with HA alone, 50 (61.0%) were classified as group C after demonstrating PCOM. Fifty-five subjects had OD alone, 37 (67.3%) of which were classified as group D based on PCOM. In total, 137/454, or 30.2% of subjects required TVUS for diagnosis or exclusion of PCOS. Conclusions: TVUS was necessary in less than one-third of subjects, primarily identifying PCOS groups C or D. Selective use of ovarian ultrasonography may reduce the costs and complexity of epidemiological and clinical studies for PCOS.

Economic Burden of Endometrial Cancer Associated With Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged females, and women with PCOS are at increased risk for endometrial cancer (EndoCA), the most common gynecological malignancy. Our study sought to assess the economic burden associated with EndoCA in PCOS. METHOD: Using PRISMA systematic review guidelines, we evaluated studies on EndoCA rates in patients with PCOS. Excluded studies were reviews and case reports, non-human subjects, without controls, without full text available, or reporting solely on other conditions. Selected studies were assessed for quality using the Newcastle-Ottawa Scale (NOS). Meta-analysis used DerSimonian-Laird random effects model to assess pooled risk ratio (RR). Excess cost was assessed in U.S. dollars (USD). RESULT: Of 98 studies screened, nine were included. Pooled RR for EndoCA in PCOS was 3.46 (95% CI 2.28-5.23), p=<0.001. In the US, prevalence of EndoCA in patients with PCOS in 2020 was 1.712%, compared with a baseline estimated prevalence in all women of 0.489%. The excess prevalence of EndoCA attributable to PCOS was 1.223%, approximately 98,348 affected women. A population-attributable fraction of EndoCA for PCOS was 24.4%. Given estimated cost of EndoCA exceeds $1.9 billion (in 2023 USD), the economic burden of EndoCA attributable to PCOS exceeds $467 million/year. CONCLUSION: The excess annual healthcare cost for EndoCA attributable to PCOS exceeds $467 million/year (2023 USD) for the US. Although a concerning morbidity of PCOS, it is notable that the economic burden of EndoCA attributable to the disorder represents only a small fraction of its total healthcare burden.

The Association Between Obesity and Polycystic Ovary Syndrome: An Epidemiologic Study of Observational Data.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female cardiometabolic-reproductive disorder. It is unclear whether the global obesity epidemic is impacting the high PCOS prevalence. OBJECTIVE: To determine the association between the prevalence of PCOS and obesity. MATERIALS AND METHODS: A systematic review was conducted to identify population studies on PCOS prevalence globally through July 2023. Linear regression and random-effect models were applied to examine the association of mean body mass index (BMI) or obesity prevalence with the prevalence of PCOS diagnosed by 1990 National Institutes of Health (NIH), 2003 Rotterdam (Rotterdam), and 2006 Androgen Excess-PCOS (AE-PCOS) criteria. Subgroup analyses were also conducted for recruitment methods and study quality. RESULTS: Fifty-eight studies with 85 956 adults from 24 countries were included. Considering all available data, a borderline association was observed between PCOS and obesity prevalence when using the AE-PCOS but not the NIH or Rotterdam criteria. Alternatively, subgroup analysis of studies with better recruitment methods demonstrated a significant positive association of population mean BMI or obesity prevalence with PCOS prevalence when using the Rotterdam or AE-PCOS criteria, while using only high-quality studies revealed an association using NIH as well as Rotterdam and AE-PCOS criteria. Overall, we observed that a 1% increase in obesity prevalence resulted in an approximately 0.4% increase in PCOS prevalence by the Rotterdam criteria. CONCLUSION: The prevalences of PCOS and obesity appear to be modestly associated, although our data cannot establish causality. This study also emphasizes the need to undertake only high-quality studies in assessing PCOS epidemiology.

Ethnicity and the Prevalence of Polycystic Ovary Syndrome: The Eastern Siberia PCOS Epidemiology and Phenotype Study.

CONTEXT: Previous studies have shown that the prevalence of polycystic ovary syndrome (PCOS) may vary according to race/ethnicity, although few studies have assessed women of different ethnicities who live in similar geographic and socio-economic conditions. OBJECTIVE: To determine the prevalence of PCOS in an unselected multiethnic population of premenopausal women. DESIGN: A multicenter prospective cross-sectional study. SETTINGS: The main regional employers of Irkutsk Region and the Buryat Republic, Russia. PARTICIPANTS: During 2016-19, 1398 premenopausal women underwent a history and physical exam, pelvic ultrasound, and testing during a mandatory annual employment-related health assessment. MAIN OUTCOME MEASURES: PCOS prevalence, overall and by ethnicity in a large medically unbiased population, including Caucasian (White), Mongolic or Asian (Buryat), and mixed ethnicity individuals, living in similar geographic and socio-economic conditions for centuries. RESULTS: PCOS was diagnosed in 165/1134 (14.5%) women who had a complete evaluation for PCOS. Based on the probabilities for PCOS by clinical presentation observed in the cohort of women who had a complete evaluation we also estimated the weight-adjusted prevalence of PCOS in 264 women with an incomplete evaluation: 46.2 or 17.5%. Consequently, the total prevalence of PCOS in the population was 15.1%, higher among Caucasians and women of Mixed ethnicity compared to Asians (16.0% and 21.8% vs. 10.8%, pz <0.05). CONCLUSIONS: We observed a 15.1% prevalence of PCOS in our medically unbiased population of premenopausal women. In this population of Siberian premenopausal women of Caucasian, Asian and Mixed ethnicity living in similar geographic and socio-economic conditions, the prevalence was higher in Caucasian or Mixed than Asian women. These data highlight the need to assess carefully ethnic-dependent differences in the frequency and clinical manifestation of PCOS.

Ovarian Morphology in Non-Hirsute, Normo-Androgenic, Eumenorrheic Premenopausal Women from a Multi-Ethnic Unselected Siberian Population.

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women, and its diagnosis rests on three principal features: ovulatory/menstrual dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology (PCOM). Currently, data on age- and ethnicity-dependent features of PCOM remain insufficient. We aimed to estimate ethnicity- and age-dependent differences in ovarian volume (OV) and follicle number per ovary (FNPO) in a healthy, medically unbiased population of Caucasian and Asian premenopausal women, who participated in the cross-sectional Eastern Siberia PCOS epidemiology and phenotype (ESPEP) study (ClinicalTrials.gov ID: NCT05194384) in 2016-2019. The study population consisted of 408 non-hirsute, normo-androgenic, eumenorrheic premenopausal women aged 18-44 years. All participants underwent a uniform evaluation including a review of their medical history and a physical examination, blood sampling, and pelvic ultrasonography. The statistical analysis included non-parametric tests and the estimation of the upper normal limits (UNLs) by 98th percentiles for OV and FNPO. In the total study population, the upper OV percentiles did not differ by ethnicity or age group. By contrast, the UNL of FNPO was higher in Caucasian women than in Asian women, and women aged <35 years demonstrated a higher UNL of FNPO compared to older women. In summary, these data suggest that the estimation of FNPO, but not OV, should take into account the ethnicity and age of the individual in estimating the presence of PCOM.

Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case-control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes. RESULTS: The study comprised 254,588 women (5,937 cases and 248,651 controls) from individual studies performed in Australia, Estonia, Finland, the Netherlands and United States of America, and separated according to three BMI stratifications (lean, overweight and obese). Genome-wide association analyses were performed for each stratification within each cohort, with the data for each BMI group meta-analysed using METAL software. Almost half of the total study population (47%, n = 119,584) were of lean BMI (≤ 25 kg/m2). Two genome-wide significant loci were identified for lean PCOS, led by rs12000707 within DENND1A (P = 1.55 × 10-12) and rs2228260 within XBP1 (P = 3.68 × 10-8). One additional locus, LINC02905, was highlighted as significantly associated with lean PCOS through gene-based analyses (P = 1.76 × 10-6). There were no significant loci observed for the overweight or obese sub-strata when analysed separately, however, when these strata were combined, an association signal led by rs569675099 within DENND1A reached genome-wide significance (P = 3.22 × 10-9) and a gene-based association was identified with ERBB4 (P = 1.59 × 10-6). Nineteen of 28 signals identified in previous GWAS, were replicated with consistent allelic effect in the lean stratum. There were less replicated signals in the overweight and obese groups, and only 4 SNPs were replicated in each of the three BMI strata. CONCLUSIONS: Genetic variation at the XBP1, LINC02905 and ERBB4 loci were associated with PCOS within unique BMI strata, while DENND1A demonstrated associations across multiple strata, providing evidence of both distinct and shared genetic features between lean and overweight/obese PCOS-affected women. This study demonstrated that PCOS-affected women with contrasting body weight are not only phenotypically distinct but also show variation in genetic architecture; lean PCOS women typically display elevated gonadotrophin ratios, lower insulin resistance, higher androgen levels, including adrenal androgens, and more favourable lipid profiles. Overall, these findings add to the growing body of evidence supporting a genetic basis for PCOS as well as differences in genetic patterns relevant to PCOS BMI-subtype.

Alterations in nonesterified free fatty acid trafficking rather than hyperandrogenism contribute to metabolic health in obese women with polycystic ovary syndrome.

OBJECTIVE: To determine whether alterations in nonesterified fatty acid (NEFA) dynamics or degree of hyperandrogenism (HA) contribute to the difference in insulin sensitivity between women with metabolically healthy obese polycystic ovary syndrome (PCOS) (MHO-PCOS) and women with metabolically unhealthy obese PCOS (MUO-PCOS). DESIGN: Prospective cross-sectional study. SETTING: Tertiary-care academic center. PATIENTS: One hundred twenty-five obese women with PCOS. INTERVENTION: Consecutive obese (body mass index [BMI] ≥ 30 kg/m2) oligo-ovulatory women (n = 125) with PCOS underwent an oral glucose tolerance test and a subgroup of 16 participants underwent a modified frequently sampled intravenous glucose tolerance test to determine insulin-glucose and -NEFA dynamics. MAIN OUTCOME MEASURES: Degree of insulin resistance (IR) in adipose tissue (AT) basally (Adipo-IR) and dynamically (the nadir in NEFA levels observed [NEFAnadir], the time it took for NEFA levels to reach nadir [TIMEnadir], and the percent suppression in plasma NEFA levels from baseline to nadir [%NEFAsupp]); peak lipolysis rate (SNEFA) and peak rate of NEFA disposal from plasma pool (KNEFA); whole-body insulin-glucose interaction (acute response of insulin to glucose [AIRg], insulin sensitivity index [Si], glucose effectiveness [Sg], and disposition index [Di]); and HA (hirsutism score, total and free testosterone levels, and dehydroepiandrosterone sulfate levels). RESULTS: A total of 85 (68%) women were MUO-PCOS and 40 (32%) were MHO-PCOS using the homeostasis model of assessment of IR. Subjects with MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, waist-to-hip ratio, HA, and lipoprotein levels. By a modified frequently sampled intravenous glucose tolerance test, eight women with MUO-PCOS had lesser Si, KNEFA, and the percent suppression in plasma NEFA levels from baseline to nadir (%NEFAsupp) and greater TIMEnadir, NEFAnadir, and baseline adipose tissue IR index (Adipo-IR) than eight subjects with MHO-PCOS, but similar fasting NEFA levels and SNEFA. Women with MUO-PCOS had a higher homeostasis model of assessment-ß% and fasting insulin levels than women with MHO-PCOS. In bivalent analysis, Si correlated strongly and negatively with Adipo-IR and NEFAnadir, weakly and negatively with TIMEnadir, and positively with KNEFA and %NEFAsupp, in women with MUO-PCOS only. CONCLUSION: Independent of age and BMI, women with MUO-PCOS have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, compared with women with MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese women with PCOS.

Influence of Phenotypes on the Metabolic Syndrome of Women with Polycystic Ovary Syndrome over a Six-Year Follow-Up in Brazil.

BACKGROUND: We followed polycystic ovary syndrome (PCOS) women with metabolic syndrome (MS) over a six-year treatment period and evaluated the influence of PCOS phenotypes on MS and on the risk for type 2 diabetes mellitus (T2DM). METHODS: This was an observational study of 457 PCOS women, whose demographic, clinical, hormonal, and metabolic data underwent analysis. The PCOS women were divided into four groups per NIH recommendations. RESULTS: After a follow-up of a mean of six years (1-20 years), 310 patients were selected to assess the development of T2DM and MS. The clinical and biochemical parameters, along with the Rotterdam phenotypes, were evaluated. Data were analyzed using Student's t- and the Pearson chi-square tests for data variation and group proportions, respectively. Additionally, multivariate analysis was applied to evaluate the effect of PCOS phenotypes on the risk for MS and T2DM. Patients of the four PCOS phenotypes did not differ in age, body mass index, total testosterone, insulin resistance, and dyslipidemia, but phenotype A patients showed the highest risk for T2DM. A decrease in androgen levels was not followed by an improved metabolic profile; instead, there was a significant increase in the number of T2DM cases. CONCLUSION: Phenotype A women are at the highest risk for type 2 diabetes mellitus.

Direct economic burden of mental health disorders associated with polycystic ovary syndrome: Systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is the most common hormone disorder affecting about one in seven reproductive-aged women worldwide and approximately 6 million women in the United States (U.S.). PCOS can be a significant burden to those affected and is associated with an increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression. We undertook this study to determine the excess economic burden associated with MH disorders in women with PCOS in order to allow for a more accurate prioritization of the disorder as a public health priority. Methods: Following PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021, for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer reviewed. As anxiety, depression, eating disorders, and postpartum depression were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian-Laird random effects model to compute pooled estimates of prevalence ratios (PRs) for the associations between PCOS and these MH disorders and then calculated the excess direct costs related to these disorders in U.S. dollars (USD) for women suffering from PCOS in the U.S. alone. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results: We screened 78 articles by title/abstract, assessed 43 articles in full text, and included 25 articles. Pooled PRs were 1.42 (95% confidence interval [CI]: 1.32-1.52) for anxiety, 1.65 (95% CI: 1.44-1.89) for depression, 1.48 (95% CI: PR: 1.06-2.05) for eating disorders, and 1.20 (95% CI: 0.96-1.50) for postpartum depression, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $1.939 billion/yr, $1.678 billion/yr, and $0.644 billion/yr in 2021 USD, respectively. Postpartum depression was excluded from the cost analyses due to the non-significant meta-analysis result. Taken together, the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $4.261 billion/yr in 2021 USD. Conclusions: Overall, the direct healthcare annual costs for the most common MH disorders in PCOS, namely anxiety, depression, and eating disorders, exceeds $4 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $15 billion yearly, considering the costs of PCOS diagnosis, and costs related to PCOS-associated MH, reproductive, vascular, and metabolic disorders. As PCOS has much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder. Funding: The study was supported, in part, by PCOS Challenge: The National Polycystic Ovary Syndrome Association and by the Foundation for Research and Education Excellence.

Polycystic Ovary Syndrome (PCOS) affects one in seven reproductive-age women worldwide. PCOS impacts women's physical and mental health, and it may also have detrimental effects on their social lives, academic achievement and careers. Studies show women with PCOS have higher rates of depression, anxiety, eating disorders, infertility and postpartum depression compared with women without the condition. The economic burden of PCOS is enormous. Previous studies show PCOS-related economic costs totals billions of dollars. But few studies have examined the costs associated with PCOS-associated mental health care. Learning more about these costs may help policymakers and clinicians allocate resources for mental health care for women with PCOS. Yadav et al. analyzed the results of 25 studies to assess the mental health impact of PCOS and its costs. The analysis found that women with PCOS are 60% more likely to have depression or anxiety compared to women without the condition. They were also twice as likely to have eating disorders. Caring for these mental health issues in PCOS patients increases US healthcare costs by approximately $4.2 billion yearly. These costs raise the healthcare-related economic burden of treating PCOS and associated conditions to $15 billion in the United States each year. The analysis suggests that earlier recognition and better treatment of PCOS could reduce associated healthcare costs and improve the quality of life for women with PCOS. The results may help policymakers and clinicians understand the condition's impact and prioritize resources for PCOS care. More research on the condition is necessary to reduce the enormous economic and personal burden caused by it.

Adipose Tissue Dysfunction in Polycystic Ovary Syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity. METHODS: We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS. RESULTS: Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS. CONCLUSION: AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.

Prospective Cohort Study Quantifying the Effect of the LevaLap 1.0 on the Distance between the Abdominal Wall and Intra-abdominal Viscera.

STUDY OBJECTIVE: More than 13 million laparoscopic procedures are performed globally every year. The LevaLap 1.0 device may facilitate safe abdominal access when using the Veress needle for initial abdominal insufflation during laparoscopic surgery. We undertook this study to test the hypothesis that use of the LevaLap 1.0 would increase the distance from the abdominal wall to underlying viscera and the retroperitoneum, including from major vessels. DESIGN: Prospective cohort study. SETTING: Referral center. PATIENTS: Eighteen patients scheduled to undergo an interventional radiology procedure under general anesthesia and muscle relaxation. INTERVENTIONS: Application of the LevaLap 1.0 device on the umbilicus and on Palmer's point, during computed tomography scanning. MEASUREMENTS: Distance from the abdominal wall to the underlying bowel and to retroperitoneal blood vessels and more distant intra-abdominal organs before and after vacuum was applied to the LevaLap 1.0. MAIN RESULTS: The device did not significantly increase the distance from the abdominal wall to the immediate underlying bowel. Alternatively, the LevaLap 1.0 created a significant increase in the distance between the abdominal wall at the access point and more distant intra-abdominal organs at the umbilicus and at Palmer's point (mean ± SD: +3.91 ± 2.32 cm, p = .001, and +3.41 ± 3.12 cm, p = .001, respectively). At the umbilicus, the device increased the distance between the abdominal wall and the anterior wall of the vena cava by +5.32 ± 1.22 cm (p = .004) or the anterior wall of the aorta by 5.49 ± 1.40 cm (p = .004). At Palmer's point, the device increased the distance between the anterior abdominal wall and the colon and/or small bowel by 2.13 ± 1.81 cm (p = .023). No adverse events were reported. CONCLUSIONS: The LevaLap 1.0 increased the distance between abdominal wall and major retroperitoneal blood vessels by >5 cm, promoting safer access during Veress needle insufflation when performing laparoscopic surgery.

The polycystic ovary syndrome: the first 150 years of study.

The communities of reproductive medicine and reproductive sciences have been witness to an enormous acceleration of interest in polycystic ovary syndrome (PCO) since the mid-19th century. Although progress has been increasingly palpable, the fundamentals of the etiology and pathophysiology of PCO remain as elusive as ever. Particularly lacking is a requisite understanding of events at the cellular and molecular levels. As we cross the millennial divide, it appears appropriate that an interim progress report be crafted. This treatise is attempting to meet this objective. What follows traces the chronology of the recorded history of PCO in 4 parts.

Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome.

Hormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day × 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. (p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.

Racial and ethnic disparities in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that impacts women worldwide. There are several racial and ethnic differences in PCOS phenotypes and in PCOS- associated metabolic dysfunction. In this review, we summarize the current literature on disparities in the diagnosis and outcomes associated with PCOS in the United States. Future studies are needed to address gaps in knowledge for racial and ethnic-specific differences in PCOS, and include a large number of non-White and/or Hispanic participants in PCOS studies.

Regional Variation in Hormonal and Metabolic Parameters of White and Black Women With PCOS in the United States.

CONTEXT: Ongoing research is needed to determine geo-epidemiologic differences of polycystic ovary syndrome (PCOS). OBJECTIVE: Determine hormonal and metabolic parameters of women with PCOS in 2 environments. METHODS: Prospective cohort study. SETTING: Tertiary-care based specialty clinics in Alabama and California. PATIENTS OR OTHER PARTICIPANTS: A total of 1610 women with PCOS by National Institutes of Health Criteria from 1987 to 2010. INTERVENTIONS: Interview, physical examination, laboratory studies. MAIN OUTCOMES MEASURES: Demographic data, menstrual cycle history, and hormonal and metabolic parameters were collected. Hirsutism was defined as modified Ferriman-Gallwey scores ≥4. Androgen values greater than laboratory reference ranges or >95th percentile of all values were considered elevated (hyperandrogenemia). Metabolic parameters included body mass index (BMI), waist-hip-ratio (WHR), glucose tolerance test, and homeostatic model assessment for insulin resistance (HOMA-IR) scores. RESULTS: Alabama women with PCOS were younger with a higher BMI. After adjustment for age and BMI, Alabama women with PCOS were more likely hirsute (adjusted odds ratio [aOR], 1.8; 95% CI, 1.4-2.4; P < 0.001), with elevated HOMA-IR scores (adjusted beta coefficient 3.6; 95% CI, 1.61-5.5; P < 0.001). California women with PCOS were more likely to have hyperandrogenemia (free testosterone aOR, 0.14; 95% CI, 0.11-0.18; P < 0.001; total testosterone aOR, 0.41; 95% CI, 0.33-0.51). Results were similar when stratified by White race. In Black women with PCOS, BMI and WHR did not differ between locations, yet differences in androgen profiles and metabolic dysfunction remained. CONCLUSION: Alabama women with PCOS, regardless of Black or White race, were more likely hirsute with metabolic dysfunction, whereas California women with PCOS were more likely to demonstrate hyperandrogenemia, highlighting potential environmental impacts on PCOS.

Ovarian volume as an independent marker for metabolic dysfunction in women with suspected androgen excess.

Objective: To determine whether ovarian volume (OV) alone is an independent marker for metabolic dysfunction in women with suspected androgen excess. Design: Retrospective cohort study. Setting: Tertiary academic reproductive endocrinology clinic. Patients: Women aged ≥21 years recruited/referred for symptoms related to androgen excess. Interventions: Transvaginal ovarian ultrasound, physical and medical evaluation, 2-hour 75-g oral glucose tolerance test (oGTT), and blood sampling. Main Outcome Measures: Prevalence of hyperandrogenism and metabolic dysfunction. Results: This study included 666 women, of whom 412 (61.9%) and 254 had OVs of >10 and ≤10 mL, respectively. An OV of >10 mL was associated with a higher prevalence of hirsutism (65.1% vs. 51.5%) than an OV of ≤10 mL. Polycystic ovary syndrome by the National Institutes of Health 1990 criteria was found in 67.3% and 51.4% of women with OVs of >10 and ≤10 mL, respectively. Metabolic parameters, including body mass index, waist circumference, and 1-hour insulin levels during the oGTT (odds ratio, 1.98; 95% confidence interval, 1.18-3.31), were significantly higher in women with an OV of >10 mL than in those with an OV of ≤10 mL. An OV of ≤10 mL had a 76.3% negative predictive value for hyperinsulinemia at 1 hour. Conclusions: In women with suspected androgen excess, an OV of >10 mL in at least 1 ovary is not associated with metabolic syndrome but is associated with younger age; an increased body mass index and waist circumference; a higher prevalence of hirsutism, oligoovulation, and polycystic ovary syndrome; and a higher 60-minute insulin level during the oGTT. Overall, an increased OV appears to be a good marker for hyperinsulinemia and hyperandrogenism in women suspected of having an androgen excess disorder.

History of Polycystic Ovary Syndrome, Premature Adrenarche, and Hyperandrogenism in Pediatric Endocrinology.

Descriptions of probable PCOS can be found in ancient Roman writings and in Renaissance art. Attention to domesticated animal reproduction led ancient observers to understand the role of the testes in male phenotypes, proven experimentally by testicular transplantation (in chickens) in 1849. Testosterone was isolated and its structure determined in the 1930s, but the multiple pathways of androgen synthesis have only been delineated recently. Adrenarche as an event separate from puberty was described in 1937, but the mechanism(s) triggering its onset remains unclear, although most work points to intraadrenal events. The identification of 11-ketotestosterone as the principal adrenal androgen is very recent (2018). Definitions of PCOS have evolved with the elucidation of its complex biology. PCOS is now recognized as a complex disorder characterized by irregular menses and hyperandrogenism often associated with infertility; its prevalence may be as high as 20% of reproductive age women. Work in the 1980s associated premature exaggerated adrenarche with PCOS, linking the adrenal to an "ovarian" syndrome. Obesity has long been noted in many patients with PCOS, and associated insulin resistance was noted in the 1980s, possibly associated with fetal developmental events such as low birth weight, but the mechanistic link between carbohydrate metabolism and hyperandrogenism remains unclear, despite intensive investigation. Genome-wide association studies have identified apparently associated genes, but mechanistic links are apparent for only some of these. Adrenarche, PCOS, and adrenal and ovarian hyperandrogenism remain very active areas of clinical and basic research.