Diagnosis Of PCOS Research Articles

62. Accuracy of Polycystic Ovarian Syndrome Diagnosis in the Adolescent Population

<h3>Background</h3> Historically, PCOS diagnosis for adolescents has been based on adult criteria. Since PCOS symptoms commonly overlap with normal pubertal changes, the Pediatric Endocrine Society developed a diagnostic criteria for PCOS in adolescents in December 2015. The purpose of this study is to assess the rate of correct diagnosis of PCOS in the adolescent population (age 10-19) at Lehigh Valley Health Network, based on Pediatric Endocrine Society (PES) expert consensus criteria. <h3>Methods</h3> We conducted a descriptive study which was a retrospective case series, using our institution's electronic medical record system. All female patients between the ages of 10-19 who were given the diagnosis of PCOS between Jan 1, 2012 to March 31, 2020 were included in the study. Patients with existence of non-PCOS causes for hyperandrogenic anovulation were excluded. If diagnosis of PCOS was made at an outside facility or if no initial note for diagnosis was found, these patients were excluded from the study as well. Study charts were reviewed to see if patients met the PES criteria for PCOS at the time the PCOS diagnosis was given. <h3>Results</h3> Out of the 40 patients in the study, 18 (45.0%) patients met the PES criteria for PCOS at the time the diagnosis was given. In the Ob/Gyn department, 7 out of 18 patients (38.9%) met the PES criteria for PCOS. In the adolescent medicine department, 7 out of 13 patients (53.9%) met the PES criteria. In the family medicine department, 1 out of 3 patients (33.3%) met PES criteria. In the pediatric endocrinology department, 3 out of 6 patients (50%) met the PES criteria. Out of the 40 patients in the study, 36 patients (90%) did meet the Rotterdam criteria for PCOS, which is not the standard for diagnosis of PCOS in the adolescent population. <h3>Conclusions</h3> The findings of the study indicate that more than half of the study population was over-diagnosed with PCOS based on adult criteria. The diagnosis of PCOS is often inaccurately given in the adolescent population. Most providers still use the Rotterdam criteria for diagnosis of PCOS in the adolescent population.

Characterization of polycystic ovary syndrome among Flo app users around the world

BackgroundPolycystic ovary syndrome (PCOS) is a complex and multi-faceted endocrine disorder that affects 5–20% of women. Literature is limited regarding potentially differing PCOS phenotypes among women around the world.ObjectiveTo use Flo app technology to understand the multifaceted characteristics of PCOS across several countries and identify contributing risk factors to the development of this condition.Study designFlo is a widely used female health and wellbeing app with period tracking functionality that provides a globally representative and medically unbiased perspective on PCOS symptomatology. A chatbot dialog on PCOS was subsequently administered on the Flo application (app) to users from 142 countries (with at least 100 respondents) who have the app running in English during September–October 2019.ResultsFor analyses, we selected the five countries with the greatest number of respondents: US (n = 243,238), UK (n = 68,325), India (n = 40,092), Philippines (n = 35,131), and Australia (n = 29,926). Bloating was the most frequently reported symptom among PCOS-positive women and appeared to be the main predictor of PCOS in our model (odds ratio 3·76 [95% CI 3·60–3·94]; p < 0·0001). Additional top predictors of PCOS are high blood cholesterol and glucose levels. As BMI increased, the percentage of women who reported a physician-confirmed PCOS diagnosis also increased. However, women in India did not follow this trend.ConclusionOur findings are based on the largest known PCOS dataset and indicate that symptoms are more complex than previously understood. The most frequently reported symptoms (bloating, facial hirsutism, irregular cycles, hyperpigmentation, and baldness) are broader than those included in the Rotterdam criteria. Future work should reevaluate and refine the criteria utilized in PCOS diagnosis.

Prevalence threshold of screening tests in obstetrics and gynecology

ObjectiveWe define the prevalence threshold as the prevalence level below which a test’s positive predictive value (PPV) declines most sharply relative to disease prevalence – and thus the rate of false positive results/false discovery rate increases most rapidly. The objective of this study is to determine the prevalence threshold of various screening tests used in obstetrics and gynecology among low-risk women in modern clinical practice. MethodsWe searched Medline, EMBASE, Google Scholar, Scopus, ISI Web of Science, Cochrane database, and PubMed to obtain the sensitivity and specificity estimates for the following screening tests: 50 g-oral glucose tolerance test (GDM-50 g), non-invasive prenatal testing (NIPT), combined first trimester screening (FTS), vagino-rectal swab for group B streptococcus (GBS) in pregnancy, cervical cytology (Pap) and HPV testing, mammography and manual breast exam, urinary PCR and cervical-vaginal swab testing for gonorrhoea and chlamydia as well as AMH for the diagnosis of PCOS. We used these estimates to calculate disease-specific prevalence thresholds, comparing them to the actual estimates of disease prevalence. ResultsThe prevalence thresholds and average estimates of disease prevalence (shown in brackets) are as follows: GDM-50 g 31 % (6%), NIPT 7% (0.2 %), combined FTS 19.5 % (0.2 %), GBS swab 18 % (15–45 %), Pap 21 % (0.2 %), HPV 27 % (0.2 %), mammography 25 % (12.5 %), breast exam 25 % (12.5 %), gonorrhoea -chlamydia 6–13 % (4.2–4.7 %), AMH for PCOS 32 % (10 %). ConclusionThe prevalence thresholds of various screening tests used in obstetrics and gynecology are well above the estimated disease prevalence. This implies that when undertaking population-level screening a significant proportion of positive screening tests obtained are likely false-positives. Attempts at individualizing pre-test probability when undertaking population-level screening are needed in order to best interpret the results of screening tests.

Polycystic Ovarian Morphology in Normocyclic Non-hyperandrogenic Adolescents.

To understand whether polycystic ovarian morphology (PCOM) represents a transient phase, and whether an increased stroma could help to characterize the phenotype of the ovary in adolescence. Cross-sectional population-based study on high-school students in Cagliari, Italy. The study population consisted of 257 normocyclic non-hyperandrogenic girls selected from a sample of 600 healthy volunteers recruited from 2012 to 2016. Clinical examination, medical history, blood sampling, and pelvic ultrasound (US) were performed. Postmenarchal years and body mass index (BMI) were estimated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β estradiol (E2), total testosterone (tT), delta-4-androstenedione (A), and 17-hydroxyprogesterone (17-OHP) were measured. Ovarian volume, follicular number per section (FNPS), and S/A ratio were measured by pelvic US. Following the Rotterdam guidelines for US PCOS diagnosis and setting the normal S/A ratio at ≤0.3, subjects were categorized into 3 groups: (1) normal ovarian morphology (NOM; n = 154, 60%); (2) polycystic ovarian morphology (PCOM) with normal S/A ratio (PCOM-NS; n = 70, 27%); and (3) PCOM with increased S/A ratio (PCOM-IS; n = 33, 13%). The NOM group had more postmenarchal years and a lower LH than both the PCOM groups, and lower A and tT than the PCOM-IS group. The PCOM-NS group had fewer postmenarchal years and lower A than the PCOM-IS group. Interestingly, unlike NOM and PCOM-NS, the prevalence of PCOM-IS remained constant among the 3 phases of postmenarchal age (10% vs 16% vs 15%, P = not significant). This study demonstrates that PCOM can be a transient condition, whereas a high S/A ratio is a stable US alteration present from early postmenarchal years.

Comparison of Body Compositions Evaluated with Bioelectrical Impedance Analysis (BIA) with Metabolic, Hormonal and Anthropometric Measurements in PCOS Patients

Aim: In this study, it was aimed to compare the body composition parameters measured by BIA(Bioelectrical Impedance Analysis) and the metabolic, anthropometric and hormonal parameters of the PCOS patients with the healthy control group and to examine the effect of PCOS on body composition parameters. It is aimed to give a better direction to PCOS follow-up and treatment. Material and Method: 23 non-obese PCOS patients were involved to this prospective study. PCOS diagnosis was made according to the Rotterdam Consensus. Antropometric, metabolic and hormonal parameters were measured. Body compositions were measured by BIA. Results: When the relationship between body composition parameters and metabolic and hormonal values were examined, significant correlations were found. There was a negative correlation between AUC-insulin levels and SHBG while a significant positive correlation between free testosterone in hirsute women with PCOS. There was a significant negative correlation between free testosterone level increase and body fat ratio while a significant positive correlation between SHBG and body fat ratio. There was a significant negative correlation between DHEAS and BMI and the hip circumference. When the relationship between body composition and antropometric parameters were examined, a significant positive correlation was found between BMI and body fat ratio, total body water and basal metabolic rate in women with PCOS. Conclusion: In this study, significant correlations were found between body compositions and hormonal, metabolic and anthropometric parameters in patients with PCOS. Based on these findings, we believe that BIA can play an important role in outpatient follow-up of patients with PCOS.

Treatment and Diagnosis Changes Polycystic Ovary Syndrome

Polycystic ovarian syndrome is at the present a well-known disease disturbing 6% to 25% of women of reproductive age, based on their interpretation. Over the past three decades, research has led to it becoming a disease more common to internal medicine procedures, from relative medical obscurity. It impacts many processes and allows for an advanced health care approach for successful diagnosis. Metabolic disorders and related complications include insulin and diabetic resistance, hyperlipidemia, elevated blood pressure, fatty liver syndrome and sleep apnea. Oligo-/amenorrhea, endometrial hyperplasia and cancer are all reproductive complications. Depression and disordered behavior are both linked to psychosocial problems. Cosmetic problems may include hirsutism, androgenic alopecia and acne. The diagnosis of PCOS takes place only if the patients have at least 2 of the 3 symptoms, namely high (High Androgen level, Presence of ovarian cysts and Irregular Periods). Diagnosis is confirmed following a pelvic exam, blood tests along with an ultrasound to determine the structure of the ovaries. This analysis addresses the mnemonic "MY PCOS" in a multiple system approach and explores the diagnosis and therapeutic strategies for developmental, cosmetic and metabolic complications. This paper gives an analysis of polycystic ovary syndrome treatment for females. The debate must emphasize the various particular issue to be dealt with in the management of this situation mnemoic "MY PCOS".

Clinical profile of PCOS patients at a tertiary care center in Gandaki Province of Nepal

Background: Polycystic Ovary Syndrome is one of the most common cause of anovulation in women of reproductive age, with a prevalence of upto 10%. Oligomenorrhea, hirsutism and obesity together with enlarged polycystic ovaries are the diagnostic criteria of PCOS. These women are vulnerable to type II diabetes, dyslipidemia, premature arteriosclerosis, and endometrial carcinoma.&#x0D; Aims and Objectives: The aim and objective of this study was to see the various clinical profile of PCOS patients at a Medical College in Nepal and to make patients aware about the long term sequalae associated with it.&#x0D; Materials and Methods: This was a retrospective study conducted in the outpatient department of Obstetrics and Gynaecology at Manipal Teaching Hospital from January 2018 till June 2019. A total of 90 patients presenting with oligomenorrhoea, obesity, acne, infertility and hirsutism were included in the study. The exclusion criteria were young women who had their menarche less than 2 years back, women older than 45 years, and patients on exogenous estrogen or progesterone therapy.&#x0D; Results: Out of 90 patients studied, 37(41%) were married and 53(59%) were unmarried. There were many patients from urban compared to rural areas (67% vs 33%). Many patients were either overweight (22%) or obese (61%) and 6% of the patients were underweight. Mean age at the time of presentation was 31.66 years with many patients (37%) between 30-35 years age group. Majority of the patients were either oligomenorrhoeic or amenorrhoeic (78 %). Weight gain was present in 83% of the patients. Infertility was present in 81% of the married patients. Fifteen women (17%) had hypothyroidism and were receiving treatment for the same. Ultrasonography was done in all the patients and typical necklace pattern of follicular arrangement was seen in 70 (78%) patients.&#x0D; Conclusion: The diagnosis of PCOS can be reliably predicted with the help of clinical features and sonography in women according to Rotterdam criteria. Oligomenorrhoea or amenorrhea and weight gain were main symptoms in our patients. It is important to educate and make unmarried PCOS patients aware of its association with infertility and long-term medical problems.

CHARACTERISTICS OF WOMEN WITH PCOS WHO UNDERGO ENDOMETRIAL BIOPSIES

In 2018, the International Evidence-Based Guidelines for the Assessment and Management of PCOS were released to integrate best practices for the diagnosis and treatment of PCOS. These guidelines do not include recommendations about endometrial biopsies for women with PCOS. Although patients with PCOS are at increased risk of endometrial hyperplasia and carcinoma due to unopposed estrogen and oligomenorrhea, no clear guidelines for endometrial biopsy for women with PCOS exist. The objective of this study is to assess characteristics of patients with PCOS who undergo endometrial biopsies. Retrospective chart review A retrospective chart review of women ages 12-65 who were seen at a university hospital system in 2017 with an ICD code for PCOS were identified and demographic, clinical, laboratory, and ultrasound data were collected in REDCap Database. Patient characteristics were compared for women who did and did not undergo endometrial biopsy, and results of endometrial biopsies were analyzed. Statistical analysis was performed with SAS 9.4 (Cary, NC) software with data analysis performed via t-test and Chi-square test, as appropriate, and a p-value <0.05 was considered significant. Of the 450 patients with PCOS identified, 51 patients had endometrial biopsies. Factors associated with having an endometrial biopsy performed were older age, diabetes, and irregular menses which were significantly different between the groups. Ethnicity, BMI, PCOS by updated guidelines, previous hormone treatment, and metformin use were not different between groups. Of the endometrial biopsies performed, 76% were benign, 20% had hyperplasia, and 2% had malignancy. Having diabetes, irregular menses, or older age increased the chance of endometrial biopsy being performed. As expected, a high percentage (22%) of patients with PCOS had endometrial hyperplasia or cancer on endometrial biopsy. Although most endometrial biopsies performed in our study were benign, future research is needed to establish clear guidelines for performing endometrial biopsies for women with PCOS since this group is at increased risk for endometrial hyperplasia and malignancy.

METFORMIN SHOULD BE RECOMMENDED FOR MORE PATIENTS WITH PCOS BASED ON UPDATED GUIDELINES

In 2018, the International Evidence-Based Guidelines for the Assessment and Management of PCOS were released to integrate best practices for the diagnosis and treatment of PCOS. Among these guidelines are updated recommendations for the use of metformin in patients with PCOS. These recommendations advise that patients with PCOS and BMI≥25, impaired glucose tolerance, and/or adolescents age <18 should take metformin to prevent metabolic sequelae of PCOS (1). Previously, metformin use was recommended for patients with PCOS who displayed evidence of glucose intolerance and/or hyperinsulinemia (2,3). The objective of this study was to evaluate patients with PCOS who are and should be taking metformin based on these updated recommendations. Retrospective chart review. A retrospective chart review of women ages 12-65 who were seen at a university system in 2017 with an ICD code for PCOS were identified and demographic, clinical, laboratory, and ultrasound data were collected in REDCap database. Forty-two women with a self-reported history of diabetes were eliminated to assess patients who were on metformin for PCOS. Patients with PCOS based on updated guidelines were identified with 2 out of 3 of the following criteria met 1) oligo or amenorrhea, 2) clinical and/or laboratory hyperandrogenism, 3) either ovary displaying ≥20 follicles between 2-9mm and/or volume > 10mL (1). It was determined whether the patients with PCOS based on new guidelines were currently taking metformin, and if they should be taking metformin based on updated recommendations as above. Patients with previously diagnosed PCOS were similarly analyzed, and it was determined if they should be taking metformin based on evidence of glucose intolerance and/or hyperinsulinemia. Statistical analysis was performed with SAS 9.4 (Cary, NC) software using Chi-square, and p-value <0.05 was considered significant. Significantly more women with PCOS by updated guidelines should be taking metformin than women with PCOS by previous guidelines. Using the old guidelines 12% of patients should be taking metformin which increased to 91% using the new guidelines (p<0.0001). Ninety-nine percent of patients who should be taking metformin by new guidelines meet criteria by BMI (Table 1). Based on updated guidelines, practitioners should prescribe metformin to more patients with PCOS, particularly those patients who are overweight and obese. Tabled 1PCOS, should be taking metformin (n=144)BMI ≥25142 (98.6%)Impaired glucose tolerance (A1c >5.7)22 (15.3%)Adolescence (age <18)17 (11.8%) Open table in a new tab

Comparison of PCOS phenotypes in adolescent and young adult Mediterranean women with possible PCOS.

During adolescence, PCOS features are supposed to be in evolution. Because of this, the diagnosis of PCOS in adolescence is often unclear and few studies have compared adolescent and adult PCOS phenotype distribution and features. The aim is to compare phenotypes in adolescents and young adults with PCOS. 109 girls aged from 13 to 19years were retrospectively studied. All patients had a gynecological age > 2years. 63 patients were adolescents (3-5years beyond menarche) while 46 patients were young adults (6-9years beyond menarche). Diagnosis of different PCOS phenotypes (A, B, C, D) was made according to the Rotterdam criteria. Clinical data (menstrual cycles, BMI, presence of hirsutism), androgen circulating levels (total testosterone, androstenedione, dehydroepiandrosterone sulphate) and ovarian morphology by ultrasound were assessed. 109 patients presented PCOS according to the Rotterdam criteria. Phenotype A was by far the most common phenotype (73.4%) followed by phenotype B (21.1%). Only few patients had phenotype C (4.6%) or phenotype D (0.9%). When patients were divided in two groups (adolescent and young adult patients), no significant difference in prevalence and features of the different phenotypes was observed. In this cohort of adolescent and young adult women with PCOS, the progression of age does not change the prevalence and the features of main PCOS phenotypes. It suggests that the Rotterdam criteria might be used also in adolescents, at least in those with 2 or more years of gynecological age, for the diagnosis of PCOS.

Effects of Activin A Hormone on Fertilization Capacity of PCOS Women Undergoing ICSI Cycle in Sample of Iraqi Women .

Activin is a member of the transforming growth factor-beta superfamily and is a polypeptide growth factor. Activin regulates follicle growth, gonadotropin responsiveness, steroidogenesis, oocyte maturation, ovulation, and corpus luteum function in the ovary via a local autocrine/paracrine effect. Activin measurement A level in serum and follicular fluid during the preovulatory stage in PCOS women undergoing an IVF/ICSI cycle to predict fertilization capacity earlier Fifty infertile couples, 25 with PCOS and 25 without PCOS, who attended Al Nahrain University in Baghdad, Iraq's High Institute of Infertility Diagnosis and Assisted Reproductive Technologies. The females that participated were between the ages of 18 and 40. On the day of oocyte retrieval, the level of Activin A in serum and follicular fluid was measured. Activin A levels in PCOS women's serum (activin A=1274 77.9) and follicular fluid (activin A =1038 50.3) compared to non-PCOS women's serum (activin A=453 25.74) and follicular fluid (Activin A=450 23.73). The study shows no correlation between activin A hormone with oocytes characteristics and fertilization rate in PCOS women with a significant increase of activin A hormone in the serum and FF of PCOS women compared to non PCOS women. Activin A level can predict a diagnosis of PCOS in addition to positive predictive pregnancy but not indicator of fertilization capacity in PCOS women.

Association of non-alcoholic fatty liver disease and polycystic ovarian syndrome

BackgroundPolycystic ovarian syndrome (PCOS) is a common endocrine disorder in women. Women with PCOS have androgen excess as a defining feature. They also have increased insulin resistance and obesity, which...

Depression in Girls With Obesity and Polycystic Ovary Syndrome and/or Type 2 Diabetes

ObjectivesPolycystic ovary syndrome (PCOS) is a common reproductive/metabolic condition associated with obesity, type 2 diabetes (T2D) and depression in adult women. Depression in adults is related to PCOS dermatologic manifestations. Adolescents with obesity with or without T2D have elevated depression symptoms, but data from youth with PCOS and obesity with/without T2D are limited. MethodsOur study included girls, aged 11 to 17 years, with obesity and PCOS, PCOS+T2D or T2D, who were newly seen in an obesity complications clinic after March 2016. All participants had Center for Epidemiologic Studies—Depression (CES-D, 20 items) scores obtained within 6 months of PCOS or T2D diagnosis. Data on history of psychiatric diagnosis and treatment, metabolic syndrome and severity of acne and hirsutism were collected through chart review. ResultsOne hundred five girls (47 with PCOS, 14 with PCOS+T2D, 44 with T2D) had similar age (15±1.8 years) and body mass index z scores (2.2±0.4). CES-D scores ≥16, indicating elevated depression symptoms, and CES-D scores ≥24, indicating severe depression symptoms, were observed in 60% and 30% of girls with PCOS, 78% and 71% of those with PCOS+T2D and 39% and 21% of those with T2D, respectively (p<0.0001 for both cutpoints). A higher CES-D score was not associated with severity of hirsutism or acne (p>0.05 for both). ConclusionsAdolescents with PCOS and obesity have higher rates of elevated depression symptoms compared with girls with T2D, which is not related to worse dermatologic symptoms. Because depression may impact both PCOS and T2D management and adherence to therapy, greater efforts should be made to screen for and address mental health in adolescents with PCOS and obesity, especially if T2D is present.

Identifying Women at Risk for Polycystic Ovary Syndrome Using a Mobile Health App: Virtual Tool Functionality Assessment.

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine disrupting disorder affecting about 10% of reproductive-aged women. PCOS diagnosis may be delayed several years and may require multiple physicians, resulting in lost time for risk-reducing interventions. Menstrual tracking apps are a potential tool to alert women of their risk while also prompting evaluation from a medical professional.ObjectiveThe primary objective of this study was to develop and pilot test the irregular cycle feature, a predictive model that generated a PCOS risk score, in the menstrual tracking app, Clue. The secondary objectives were to run the model using virtual test subjects, create a quantitative risk score, compare the feature’s risk score with that of a physician, and determine the sensitivity and specificity of the model before empirical testing on human subjects.MethodsA literature review was conducted to generate a list of signs and symptoms of PCOS, termed variables. Variables were then assigned a probability and built into a Bayesian network. Questions were created based on these variables. A total of 9 virtual test subjects were identified using self-reported menstrual cycles and answers to the feature’s questions. Upon completion of the questionnaire, a Result Screen and Doctor’s Report summarizing the probability of having PCOS was displayed. This provided information about PCOS and data to facilitate diagnosis by a medical professional. To assess the accuracy of the feature, the same set of 9 virtual test subjects was assigned probabilities by the feature and the physician, who served as the gold standard. The feature recommended individuals with a score greater than or equal to 25% to follow-up with a physician. Differences between the feature and physician scores were evaluated using a t test and a Pearson correlation coefficient in 8 of the 9 virtual test subjects. A second iteration was conducted to assess the feature’s probability capabilities.ResultsThe irregular cycle feature’s first iteration produced 1 false-positive compared with the physician score and had an absolute mean difference of 15.5% (SD 15.1%) among the virtual test subjects. The second iteration had 2 false positives compared with the physician score and had an absolute mean difference of 18.8% (SD 13.6%). The feature overpredicted the virtual test subjects’ risk of PCOS compared with the physician. However, a significant positive correlation existed between the feature and physician score (Pearson correlation coefficient=0.82; P=.01). The second iteration performed worse, with a Pearson correlation coefficient of 0.73 (P=.03).ConclusionsThe first iteration of the feature outperformed the second and better predicted the probability of PCOS. Although further research is needed with a more robust sample size, this pilot study indicates the potential value for developing a screening tool to prompt high-risk subjects to seek evaluation by a medical professional.

SUN-LB3 Relationship Between BMI and PCOS Symptoms Among Flo App Users in the United States

Polycystic ovary syndrome (PCOS) is known to affect 6%-12% of women of reproductive age in the United States. PCOS is a heterogeneous condition associated with menstrual cycle irregularity and androgen excess. Though many women with PCOS have a BMI classified as overweight or obese, information is limited on how specific symptoms and BMI mediate PCOS diagnoses in the general population. A questionnaire on PCOS-related symptoms and previous PCOS diagnosis was available to Flo users during one month (2019). Women aged 18-44 years seeking to track their cycle or to conceive, who were not pregnant, on active contraception or in stabilization mode after pregnancy, and had Flo app running in English met the study inclusion criteria. Participant characteristics including age and BMI were also collected from Flo app users during the sign-up process. All users in the study had agreed to the use of their de-identified and aggregated data for research purposes. The differences in clinical manifestation of PCOS symptoms between BMI groups were analyzed. Of US users with BMI data in the whole cohort, 8,808 women reported having physician-diagnosed PCOS, 5,551 women reported not having a PCOS diagnosis, and 58,478 reported that they had not been checked for PCOS. Of women with PCOS, 19.5% were normal weight (BMI 18.5-24.9), 19.7% were overweight (BMI 25.0-29.9), 20.4% were obese (30.0-34.9), 17.8% were severly obese (BMI 35.0-39.9), and 21.0% were morbidly obese (BMI 40+). The most common symptoms among PCOS positive women were bloating (38.7%), hirsutism (38.2%), and irregular cycle (26.0%). A direct relationship exists between BMI and having PCOS, as the percentage of PCOS in obese, severely obese, and morbidly obese BMI groups was higher (1.37, 1.87, and 2.12 times, respectively) than in the whole cohort. Similarly, among women who report acne, skin hyperpigmentation, bloating, hirsutism, heavy menses, baldness, family history of PCOS, high cholesterol, irregular cycle, and inability to conceive for > 1 year, there is a direct relationship between BMI and the percentage of women with PCOS. Moreover, when identifying symptoms and findings serving as strong predictors of a positive PCOS diagnosis, hirsutism, high glucose, and high levels of both cholesterol and glucose were the top symptoms and findings for women with BMI 18.5-34.9. Hirsutism, high glucose, and inability to conceive for > 1 year were the strongest predictors of PCOS for women with BMI 35+. Among all users with hirsutism, the percentage of women with PCOS increased 3.65 times compared to the whole cohort, making it the strongest predictor of PCOS. Understanding BMI patterns as they relate to PCOS symptoms allows for better understanding the pathophysiology of PCOS. Among women with PCOS in the United States, changes in BMI are associated with variations in the many symptoms of PCOS.

OR11-02 Distinctive Neuroendocrine Changes and Menstrual Dysfunction in Early Postmenarchal Daughters of Women With PCOS

PCOS is a complex genetic disease with strong familial aggregation - ~40% of reproductive-age sisters have elevated testosterone (T) levels and other features of the syndrome. Beginning in infancy, daughters of affected women (PCOS-d) have elevated anti-Müllerian hormone (AMH) levels and evidence for global increases in 5α-reductase activity. Peripubertally, PCOS-d have increased T levels. Peripubertal overweight and obesity (OB) girls also have elevated T but not AMH levels.We initiated a prospective study of PCOS-d and OB to test the hypothesis that only PCOS-d are at increased risk to develop PCOS. Herein, we present the baseline assessments in 14 PCOS-d, 14 OB, and 18 lean control girls (LC) aged 11-16 yrs who were enrolled within 2-yrs of menarche. PCOS-d mothers fulfilled NIH criteria, OB and LC mothers had no history of irregular menses or clinical hyperandrogenism. Morning blood sampling was performed for hormone levels. Free T was calculated from total T and SHBG. Ovarian MRI was performed to assess morphology. Data are mean ± SD, α=0.05.By design, age did not differ between the groups, but BMI z-score was higher in OB compared with PCOS-d and LC (1.3±1.1 PCOS-d v 2.0±0.6 OB v 0.1±0.7 LC, P<0.0001). The prevalence of irregular menses (cycles ≤ 21d or ≥ 45d apart) was significantly increased only in PCOS-d (61% PCOS-d, 23% OB, 19% LC, Χ 2 P=0.03). Total T levels did not differ between the groups. SHBG levels were decreased in PCOS-d and OB (23±16 PCOS-d v 30±16 OB v 56±15 LC, nmol/L, P<0.0001), resulting in a trend toward increased free T levels in these groups (0.6±0.3 PCOS-d v 0.6±0.5 OB v 0.4±0.2 LC, ng/dL, P=0.06). DHEAS levels were higher in PCOS-d and OB compared with LC (135±35 PCOS-d v 150±68 OB v 88±46 LC, ug/dL, P=0.05). AMH levels, follicle counts and ovarian volume did not differ.GnRH analog (GnRHa,10 µg/kg SC) stimulation was performed in 9 PCOS-d and 13 OB. Both baseline LH levels (7.6±4.4 PCOS-d v 3.7±2.1 OB, mIU/mL, P=0.01) and LH responses to GnRHa were significantly increased in PCOS-d (LH AUC: 2110±1132 PCOS-d v 1047±808 OB, P=0.01). Baseline FSH and FSH AUC did not differ. Post-GnRHa 17-OHP levels did not differ.Early postmenarchal PCOS-d but not OB have evidence for increased GnRH-mediated LH release, a cardinal feature of PCOS disordered gonadotropin secretion. The increased prevalence of irregular menses in PCOS-d is consistent with this change. In contrast, androgen levels are similarly increased in both groups. These findings align with genomewide association studies implicating gonadotropin secretion and action in PCOS pathogenesis and suggest that neuroendocrine alternations in gonadotropin release are a core causal pathway in PCOS. Moreover, these findings provide further support for our hypothesis that PCOS-d but not OB are at increased risk for PCOS. Longitudinal studies are ongoing to test this hypothesis at 2-yrs postmenarche when the diagnosis of PCOS can be established.

SAT-748 Advantages and Limitations of an Integrative Measurement for All Serum Androgens and Anti-Androgens

Background: Analytic measurements of a hormone in bodily fluids are a cornerstone of clinical evaluation. However, clinical presentation may be affected also by currently unmeasured modulators of hormonal function. An alternative could be to measure the cumulative effect of all factors present in a bodily fluid on the function of a hormone receptor. Prior studies showed an androgen receptor (AR) BioAssay to accurately measure urine androgens in males undergoing testosterone (T) supplementation (1). The factors integrated by the AR BioAssay include androgens, anti-androgens and, in serum, androgen binding proteins affecting ligand availability.Methods: The AR BioAssay was exposed to male and female serum samples obtained from the CDC’s Hormone Standardization (HoSt) Program, and to female serum samples from the UCSF PCOS Tissue Bank registry. AR activity was quantified against a testosterone standard curve and recorded as ‘T-equivalent’ (‘T-eq’) androgen activity units.Results: In 40 CDC HoSt sera added directly (no extraction) to AR BioAssay cells, androgen activities ranged from 2.57 to 298 ng ‘T-eq’/dl. In the 20 ‘male’ CDC HoSt sera (T>150 ng/dl), the androgen activity measurements were uniformly less (0.35 ± 0.10) that of the T-measurement. By contrast, in the 20 ‘female’ CDC HoSt sera, in which T concentrations are typically lower than the affinity of T for sex hormone binding globulins such that more of the T is available to the AR BioAssay, the measured androgen levels were on average 1.45-fold higher than the T concentration. This androgen to T comparison showed high variability in females with 5 of 20 CDC HoSt samples having androgen concentrations more than double that of T (maximum, 6.1-fold). In female serum samples from the PCOS registry, androgens were higher in patients with a PCOS diagnosis (57.7 +/-17.6 ng ‘T-eq’/dl; n = 23) compared to women not meeting formal PCOS criteria (38.1 +/-10.8 ng ‘T-eq’/dl; n = 4); androgen values again averaged 1.40-fold (maximum, 4.9-fold) that of the T measurements, regardless of PCOS diagnosis.Conclusions: Androgen-binding globulins appear to most influence androgen activity levels in male serum. In females, the lower T concentrations may minimize the impact of androgen-binding proteins and permit the impact of non-T androgens to be more pronounced with possible clinical consequence. Further investigations are needed to determine whether functional androgen measurements may improve clinical diagnosis of certain conditions. Reference: (1) Bailey et al (2016) PLoS One11(3):e0151860

SUN-LB6 Characterization of PCOS Among Flo App Users Around the World

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder associated with menstrual irregularity and androgen excess. The worldwide prevalence of PCOS among women of reproductive age ranges from 5-20%. Mobile menstrual cycle apps, such as Flo, provide an opportunity to gather data on the characteristics of PCOS in a globally representative and medically unbiased population. The objective of this study was to report PCOS symptomatology relative to country in order to better characterize PCOS and its differing phenotypes among users around the world. A questionnaire on PCOS related symptoms and previous PCOS diagnosis was available to Flo users during one month (2019). The geographical location of the user was estimated based on the IP address. Study inclusion criteria included women aged 18-44 years seeking to track their cycle or to conceive, who were not pregnant, on active contraception, or in stabilization mode after pregnancy and had Flo app running in English. All users in the study had agreed to the use of their de-identified and aggregated data for research purposes.The highest number of Flo app users who completed the PCOS questionnaire were coming from the following top 5 countries: United States (US) (n=240,732), United Kingdom (UK) (n=67,696), India (n=40,171), the Philippines (n=35,097), and Australia (n=28,946). The percentage of self-reported PCOS in these countries was 14.4% with higher percentages in India, the Philippines, and Australia (22.6%, 20.0%, 15.9, respectively) and lower in the US and UK (12.2% and 13.71%, respectively). In the US, UK, and Australia, the most common self-reported symptoms of PCOS positive women were bloating, hirsutism, and irregular cycles. In India and the Philippines, the most common symptoms of women with PCOS were bloating, baldness, and irregular cycles. Hirsutism, high glucose and high levels of both cholesterol and glucose are the three top symptoms increasing the probability of PCOS in all studied countries. The percentage of self-reported PCOS increases 3.04 times among users that reported hirsutism compared to all users that positively responded to the PCOS self-assessment question. Probability of PCOS among users that report hirsutism increases 3.85 times for Australia and 4.24 times for India. Australia and India had higher percentages of self-reported PCOS among those who reported experiencing nearly all PCOS related symptoms. Using Flo’s software, we are able to determine that geographic location has an effect on the phenotypic presentation of PCOS. Understanding the distribution of PCOS symptomology around the world will help to better characterize PCOS and improve diagnosis and treatment on both an individual and global scale.

Acupuncture or auricular electro-acupuncture as adjuncts to lifestyle interventions for weight management in PCOS: protocol for a randomised controlled feasibility study

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent women’s health condition with reproductive, metabolic, and psychological manifestations. Weight loss can improve these symptoms and is a key goal; however, many women find this difficult to achieve. Acupuncture is a Chinese medical treatment that involves insertion of very fine metal needles into specific areas of the body and has been shown to be efficacious for weight loss in non-PCOS populations. However, few studies have been conducted in women with PCOS. A variant of acupuncture, auricular electro-acupuncture (AEA), may have beneficial effects on sympathetic tone, which is associated with insulin resistance, obesity and PCOS.MethodsThis prospective three-arm open label parallel randomised controlled trial will assess feasibility and acceptability of acupuncture and/or AEA for weight loss in women with PCOS. We will enrol 39 women from the community aged between 18 and 45 years, with physician diagnosis of PCOS according to the Rotterdam criteria: body mass index (BMI) between 25 and 40 kg/m2. Women will be randomly allocated to receive one of three treatments for 12 weeks duration: body electro-acupuncture + lifestyle interventions, AEA + lifestyle interventions, or lifestyle interventions alone. The lifestyle intervention in this study is telephone-based health coaching (between 4 and 13 phone calls, depending on individual need), provided by the Get Healthy Service. Primary outcomes of the study are feasibility and acceptability of trial methods as determined by recruitment and retention rates, adherence, acceptability, credibility, and safety. Secondary outcomes include anthropometric (body weight, BMI, waist and hip circumference), metabolic (glucose tolerance and insulin sensitivity obtained from a 2-h 75 g oral glucose tolerance test with area under the curve insulin calculated using the trapezoid rule), reproductive (androgen levels, menstrual cyclicity, clinical hyperandrogenism using the Ferriman-Gallwey scoring system), autonomic (heart rate variability, blood pressure), lifestyle (physical activity levels, diet quality, weight self-efficacy), quality of life, and psychological (depression and anxiety symptoms, internal health locus of control).DiscussionThis study addresses the feasibility and acceptability of novel interventions to treat overweight/obesity in PCOS. Study findings have the potential to generate a new understanding of the role of acupuncture and auricular acupuncture in weight management.Trial registrationAustralian New Zealand Clinical Trial Registry, 8/6/18 ACTRN12618000975291

MicroRNA‐93, a Novel Potential Non‐Invasive Biomarker for Polycystic Ovary Syndrome (PCOS) Diagnosis

PCOS is one of the most common endocrine disorders and affects at least 7–9% of reproductive‐aged women. However, PCOS diagnosis is a challenge for physicians because of the constellation of symptoms. From our previous studies, we found that the expression of microRNA‐93 (miR‐93) was up‐regulated in adipose tissue and related to the high incident of insulin resistance in PCOS women. As a result, we generated an adipose‐selective miR‐93 overexpression mouse (miR‐93AT+ mice) model which shows a PCOS‐like phenotype by using Cre/loxP DNA recombination. The level of miR‐93 expression in tissues was investigated by the q‐PCR method. The expression of miR‐93 was specifically increased in adipose tissue but not in muscle, liver, heart, or kidney tissues in miR‐93AT+ mice. However, the level of miR‐93 was overexpressed in the blood of the miR‐93AT+ mice, similar to results found in PCOS women. In addition, the level of miR‐93 was overexpressed (2.5 fold) in the feces of miR‐93AT+ mice. These data suggest that fecal miR‐93 may be applied as a potential novel non‐invasive biomarker for the diagnosis of PCOS. Additional studies of miR‐93 expression in feces from PCOS women are required to confirm this hypothesis.Figure 1