Polycystic Ovary Syndrome Status Research Articles

Polycystic ovary syndrome increases risks of infertility: Role of a well-planned diet and other factors

Polycystic ovary syndrome (PCOS) is a hormonal disorder causing menstrual irregularities, insulin resistance, and infertility. Treatment options include medical treatments and lifestyle modifications. The guideline suggests various balanced strategies, including diet, exercise, behavioral interventions, and sleep. This article aimed to review the multiple diets, nutrients, and other factors responsible for PCOS-induced infertility, which is growing nowadays. The primary motive to recover PCOS is to reduce the risk of infertility among women. PCOS treatment involves birth control pills, diabetes medication, and estrogen receptor modulators. Lifestyle changes like resistance training and yoga can improve body composition and reduce fat. Traditional lifestyles, such as alcohol and tobacco, can hinder fertility. Weight loss improves PCOS status regardless of dietary composition. Low glycemic index diets reduce weight gain, improve insulin sensitivity, and reduce risk factors. The DASH diet, rich in fruits, vegetables, whole grains, nuts, legumes, and low-fat dairy, is recommended for managing PCOS. In conclusion, PCOS should be taken care of for young women with the help of diet, exercise, and medication, if needed, to avoid infertility under the supervision of a dietitian and physician.

Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort

Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions. To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions. This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys. Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles. The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated. The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity. These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome.

This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

Association between Dietary Inflammatory Index (DII) and the Risk of Polycystic Ovary Syndrome: A Case-Control Study

Background: Polycystic ovary syndrome (PCOS) is an inflammation-related condition and a common metabolic disorder in women at fertility ages. The Dietary Inflammatory Index (DII) is a validated nutritional tool for estimating the inflammatory potential of the diet. It is assumed that a high DII score (indicating a predominantly inflammatory diet) has an association with higher odds of PCOS. The current study aimed to investigate the association between DII and PCOS risk in women. Methods: This case-control study was conducted in 2019-2020 on 120 newly-diagnosed PCOS cases and 120 healthy controls aged 18-45 years in Khorramabad, Iran. DII was estimated based on a validated 168-item Food Frequency Questionnaire (FFQ). Results: The mean±SD of DII in PCOS patients was 0.40±2.09, while it was 0.45±1.92 in the control group (P&lt;0.001). There was a positive association between increasing DII score and the risk of PCOS (odds ratio= 2.41; 95%CI: 1.15-5.02, P for trend =0.006) in the crude model as the fourth quartile was compared with the lowest one. This association was still significant in several models after adjusting for age and energy intake (P for trend &lt;0.001), in the model adjusted for the physical activity level, education status, and family history of PCOS (P for trend=0.003), and also after additional adjustment for BMI (P for trend= 0.003). Conclusions: The present study revealed that consuming more pro-inflammatory diets with higher DII scores is related to an increased risk of PCOS.

Gut bacteriome and mood disorders in women with PCOS.

How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31years and age 46years, and stool samples were collected from the women at age 46years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. N/A.

Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. This is a retrospective study, and subjects attended for care from 2004 to 2022. Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. We could not evaluate hormonal or ultrasound parameters in controls. Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. No funding was received in support of this study. The authors have no conflicts of interest to disclose. N/A.

Hyperandrogenism associated with polycystic ovary syndrome may have a protective effect against fracture risk in female athletes: A pilot study.

Polycystic ovary syndrome (PCOS), characterized by polycystic ovaries, anovulation, and hyperandrogenism, is believed to be an evolutionary mismatch disease. Past research has examined PCOS as a uniform disease, despite variation in phenotypes across diagnostic categories, but establishing an evolutionary mismatch requires a focus on individual traits. We suggest PCOS hyperandrogenism may have been beneficial in ancestral environments because it reduced fracture risk and associated morbidity and mortality due to increased bone mineral density (BMD). We test this hypothesis by assessing fracture frequency, a proxy for BMD, in highly active females with and without PCOS hyperandrogenism. Sixty-seven reproductive-aged women were surveyed and grouped as: high intensity interval training (HIIT; a proxy for metabolic and physical stress) athletes with hyperandrogenic PCOS (31.24%), HIIT athletes without PCOS (29.85%), and nonathletes with hyperandrogenic PCOS (38.81%). Fracture occurrence was compared between the groups using independent samples Kruskal-Wallis tests for non-normally distributed data, and multiple regression analysis was used to examine anthropometrics, lifestyle and reproductive factors, PCOS status, and exercise frequency on fracture occurrence. Fracture occurrence was higher in non-PCOS athletes (3.8 ± 4.3) than PCOS-athletes (1.2 ± 1.4, p = .11) and PCOS-non-athletes (1.0 ± 1.4, p < .01). PCOS-athletes and nonathletes did not differ significantly in fracture occurrence (p = .33). These results were independent of factors associated with bone health. These preliminary findings suggest females with PCOS-related hyperandrogenism may be less likely to experience bone fractures and provide an initial step to explaining why PCOS has persisted despite marked negative reproductive consequences in modern populations.

BMI and Polycystic Ovary Syndrome: Demographic Trends in Weight and Health.

Introduction Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women in adolescence and reproductive age. The distribution of PCOS across different body mass index (BMI) categories can vary, and research has shown associations between PCOS and weight status. This study tries to evaluate the distribution of PCOS in relation to BMI in women attending the PCOS clinic in a tertiary hospital in eastern India. Methodology This hospital-based cross-sectional study was carried out in the gynecology outpatient departmentof a tertiary care center. The study population included all the women in the age group between 15 and 45 years diagnosed as having PCOSusing the Rotterdam definition. The various physical, clinical, and biochemical parameters were measured in the study population and compared among the obese and lean PCOS patients. Results and discussion A total of 143 women were included in the study. The mean age of the study population was 26.8 years. Among these, the underweight and normal weight patients were categorized as lean PCOS patients, 35 in number (24.5%), and overweight and obese patients were categorized as obese PCOS patients, 108 in number (75.5%). All the physical parametermeasures like age (mean = 28.05, SD = 5.722), height (mean = 153.384, SD = 6.679), weight (mean = 68.182, SD = 11.501), waist circumference (mean = 95.135, SD = 10.291), hip circumference (mean = 101.47, SD = 9.320), waist-to-hip ratio (mean = 0.940, SD = 0.0831), and neck circumference (mean = 34.85, SD = 2.445) were significantly higher in the obese group as compared to the lean group. Menstrual irregularity was significantly more common in the obese PCOS patients as compared to the lean PCOS group (p = 0.02). There was a significant difference (p < 0.05) between the obese and lean PCOS patients when the biochemical parameters like fasting insulin, fasting glucose, and homeostatic model assessment of insulin resistance (HOMA-IR) were compared. There is a strong link between obesity, insulin resistance, and PCOS. Obesity can exacerbate insulin resistance, a common feature of PCOS, leading to increased levels of insulin and androgens. Conclusion The demographic distribution of PCOS in relation to BMI is essential for tailoring interventions and treatments.

Validation of an Anti-Müllerian Hormone Cutoff for Polycystic Ovarian Morphology in the Diagnosis of Polycystic Ovary Syndrome in the HARMONIA Study: Protocol for a Prospective, Noninterventional Study.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women and is diagnosed using the Rotterdam criteria, including diagnosis of polycystic ovarian morphology (PCOM) by transvaginal ultrasound (TVUS). Due to high cost, availability, and the impact of the operator and ultrasound equipment on the reliability of the antral follicle count (AFC) by TVUS, an unmet need exists for a diagnostic test to determine PCOM without TVUS. A strong positive correlation between elevated anti-Müllerian hormone (AMH) levels and AFCs has been demonstrated in women with PCOS. In addition, recent updates to the international evidence-based PCOS guidelines state that serum AMH can be used as an alternative to TVUS-determined AFC, in the diagnosis of PCOM. The retrospective APHRODITE study derived and validated an AMH cutoff of 3.2 ng/mL for the Elecsys AMH Plus or Elecsys AMH assays (Roche) to diagnose PCOM in patients with PCOS. This study aims to further validate, in an independent prospective cohort, the AMH cutoff (3.2 ng/mL) for PCOM determination, which was previously derived and validated in the APHRODITE study. This large, prospective, multicenter, population-based, noninterventional study will evaluate the previously established AMH cutoff for the determination of PCOM during the diagnosis of PCOS using the Elecsys AMH Plus immunoassay in an independent population. Participants were women born between July 1985 and December 1987 in Northern Finland; the study partially links to the Northern Finland Birth Cohort 1986. We assessed the enrolled women, determined with the 2023 PCOS Guidelines, for current PCOS status and divided them by phenotype if positive. Each participant had 1 study visit to collect serum samples, record clinical data, and undergo a gynecological examination including TVUS. All data were collected by highly trained midwives or trained gynecologists. Sensitivity, specificity, and agreement measures were used to validate the previously determined cutoff in the whole population and in subpopulations based on phenotype and relevant demographic or clinical factors. The minimum target sample size was approximately 1800 women, including approximately 10% with PCOS. At the time of manuscript submission, participant recruitment had concluded, and 1803 women were enrolled into the study. Data collection is complete and biostatistical analysis is planned for 2023. To limit variability, there were few TVUS operators and only 2 TVUS machines of the same type. Additionally, all women who were taking oral contraceptives were excluded from the primary analysis population. Selection bias was limited as this was a population-based study and participants were not seeking treatment for PCOS symptoms. Validating the AMH cutoff in a large, population-based study will provide further evidence on the utility of the Elecsys AMH Plus or Elecsys AMH assays in PCOM diagnosis as an alternative to TVUS. Measuring AMH for PCOM diagnosis could reduce delayed or missed diagnoses due to operator-dependent TVUS examinations. ClinicalTrials.gov NCT05527353; http://tinyurl.com/2f3ffbdz. DERR1-10.2196/48854.

Polycystic Ovarian Syndrome and Periodontal Diseases: The Link Demystified

Polycystic Ovarian Syndrome (PCOS) is one of the most commonly diagnosed endocrine disorders, affecting 7-20% of women of reproductive age. In the case of PCOS, the ovaries have a large number of cystic follicles linked to persistent anovulation and androgen overproduction. PCOS is also linked to other systemic disorders, such as diabetes mellitus, cardiovascular disorders, and psychological conditions. Research studies indicate that PCOS may increase susceptibility to periodontal disease. The mechanisms underpinning the links between these two conditions are not completely understood. There is emerging evidence to support the existence of a two-way relationship between PCOS and periodontitis, with PCOS increasing the risk for periodontitis and periodontal inflammation worsening the PCOS status. This narrative review of the various pathophysiological mechanisms linking the two diseases depicts a positive correlation between the two conditions.

Increased body mass index is negatively associated with ovarian reserve as measured by anti-Müllerian hormone in patients with polycystic ovarian syndrome.

Anti-Müllerian hormone (AMH) is commonly used as a marker of ovarian reserve. Although obesity is associated with decreased fertility, the relationship between body mass index (BMI) and AMH remains uncertain, hindering the accurate interpretation of AMH. We sought to assess the relationship between serum AMH and BMI in patients with and without polycystic ovarian syndrome (PCOS). This study analysed 500 patients at a single centre between 2020 and 2021. Patients were divided into cohorts: those with BMI <40 kg/m2 and those with BMI >40 kg/m2. Patients with and without PCOS were included. Chi-square tests, Fisher's exact tests, multiple linear regression analysis and independent t-tests were performed as appropriate. In the general study population, serum AMH was not significantly different in the BMI >40 kg/m2 group compared to the BMI <40 kg/m2 group (4.3 ± 5.6 vs. 4.3 ± 5.6, p = .35). Patient ages between these two groups differed, with an average age of 35.4 ± 5.4 years in the BMI <40 kg/m2 group and 33.7 ± 5.4 years in the BMI <40 kg/m2 group (p = .031). Our multivariate regression analysis, which adjusted for age, demonstrated a significant interaction effect between BMI and PCOS diagnosis, indicating that the relationship between BMI and AMH is dependent on PCOS status (β = -.03, 95% confidence interval [CI]: -0.05, 0.00, p = .044). In patients without PCOS, we found a non-significant relationship between AMH and BMI (β = .00, 95% CI -0.01, 0.01, p = .7); however, in patients with PCOS, AMH significantly decreased as BMI increased (β = -.03, 95% CI -0.06, 0.00, p = .034). BMI has an inverse association with AMH levels in patients with PCOS, indicating a need for future research to determine if that interaction represents a clinically significant negative effect on reproductive function.

Insulin-like growth factor binding protein-1 and insulin in polycystic ovary syndrome: a systematic review and meta-analysis.

Insulin-like growth factor binding protein-1 (IGFBP-1) is considered a decline in polycystic ovary syndrome (PCOS), but it remains controversial that whether such reduction is attributed to obesity. This systematic review aims to explore whether IGFBP-1 is reduced in PCOS, and whether such reduction is associated with obesity. Our pooled study included 12 studies with a total of 450 participants. IGFBP-1 levels in PCOS were significantly lower than that in non-PCOS (SMD (95%CI)=-0.49(-0.89, -0.09), P=0.02). No significant difference in IGFBP-1 levels between patients with or without PCOS classified by BMI. Whilst, stratification by PCOS status revealed a significant decrease in IGFBP-1 in overweight (SMD (95%CI)=-0.92(-1.46, -0.37), P=0.001). When comparing fasting insulin in the same way, PCOS patients had significantly elevated fasting insulin level but not statistically declined IGFBP-1 after classified by BMI. This meta-analysis provides evidence that the decrease of IGFBP-1 in PCOS was more strongly influenced by comorbid obesity than by PCOS itself. Additionally, contrast to previous findings that insulin significantly suppresses IGFBP-1, our results suggested that the suppression of PCOS-related hyperinsulinemia on IGFBP-1 seemed diminished. Overall, our work may provide a novel perspective on the mechanism between insulin and IGFBP-1 underlying PCOS development.

Abstract 15904: Hypertension Risk in Adolescent Females With Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is associated with increased risk of hypertension (HTN) in adult women, but fewer studies have examined PCOS and HTN among adolescents. Characterizing blood pressure (BP) by PCOS status prior to adulthood may inform early cardiovascular risk surveillance efforts. Aim: To examine the prevalence of hypertension-range BP (HTN-BP) in adolescent females with and without PCOS and to characterize the association of PCOS and HTN-BP. Methods: We used data from an existing cohort of 171,855 females aged 13-17y in a US healthcare system with well-child visit (2012-2018) and measured systolic/diastolic BP. The 2017 American Academy of Pediatrics Practice Guideline was used to classify normal BP [&lt;120/&lt;80], elevated BP [120/&lt;80-129/&lt;80], stage 1 HTN [130/80-139/89] and stage 2 HTN [≥140/90 mmHg]. PCOS was based on clinical diagnosis (ICD-9 265.4, ICD-10 E28.2) within 1 year of the visit. Body mass index (BMI) was classified as healthy, overweight, moderate and severe obesity using BMI percentile data; 3062 underweight females were excluded from analyses. Differences by PCOS (N=1142) and no PCOS (N=167,651) status were compared. Multivariable logistic regression examined the association of PCOS and HTN-BP, with adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: The cohort included 168,793 females (33.6% non-Hispanic White, 9.7% Black, 30.5% Hispanic, 19.9% Asian/Pacific Islander, and 6.3% other/unknown race ethnicity), of whom 65.9% had healthy weight, 18.7% overweight, and 15.4% obesity. Based on visit BP data, 75.6% were normotensive, 17.5% had elevated BP, and 7.0% had HTN-BP (6.1% Stage 1, 0.9% Stage 2). HTN-BP prevalence was much higher for PCOS vs no PCOS (18.6% vs 6.9%, p&lt;0.001). After accounting for age, race/ethnicity, and BMI level, PCOS was associated with 1.3-fold greater odds of HTN-BP (aOR 1.3, CI 1.1-1.5). Similar findings were seen among females with obesity (aOR 1.3, CI 1.1-1.6). Conclusions: Prevalence of HTN-BP was 30% higher for those with PCOS after adjusting for BMI, race/ethnicity, and age. Similar findings were evident among those with obesity. Future studies should examine persistent HTN and the independent association of PCOS and HTN severity in this high-risk population.

Examining the proportions of food addiction among women with and without polycystic ovarian syndrome who do and do not take hormonal birth control

Polycystic ovarian syndrome (PCOS) is a reproductive disorder driven by insulin resistance. Insulin resistance may increase weight gain and increase the rewarding intake of ultra-processed foods (UPFs). Individuals with PCOS may be more susceptible to the reinforcing properties of UPFs, increasing the risk to consume UPFs in addictive-like ways, operationalized by food addiction (FA). Additionally, hormonal birth control, commonly prescribed to women with PCOS, are found to increase food cravings and overeating. This study examined the relationships between PCOS status, FA, and hormonal birth control use. The study sample (N = 365, assigned female at birth) was drawn from Amazon Mechanical Turk, with half of the sample (n = 181) reporting having PCOS and the other half not (n = 184). Participants answered questions about women's reproductive health (i.e., PCOS, hormonal birth control use) and completed the modified Yale Food Addiction Scale 2.0 (mYFAS 2.0). A chi-square test found that 51.9 % of participants with PCOS (M = 6.23, SD = 3.82) met diagnostic criteria for FA (assessed by the mYFAS 2.0) compared to 16.8 % of participants without PCOS (M = 2.47, SD = 3.39). A hierarchical linear regression found independent main effects of PCOS status (β = 0.40, t(352) = 8.61, p < .001) and hormonal birth control use (β = 0.16, t(351) = 3.59, p < .001), to be associated with higher mYFAS symptom count scores. No differences were found between the types of hormonal birth control participants reported taking. The finding suggests that FA is an overlooked, understudied psychological condition impacting these individuals in weight loss treatments. Future studies are needed to understand the relationship between FA and PCOS in clinical samples.

Correlation between phenotype and cortisol with anxiety status related to Polycystic Ovary Syndrome (PCOS)

Link of Video Abstract: https://youtu.be/VpTspeX7fe0 Background: Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Symptoms include irregular menstrual cycles, hirsutism, obesity, acne vulgaris, and infertility. PCOS is a stigmatized condition that affects women's identity and mental health, especially anxiety. In addition, increased cortisol is associated with increased anxiety. This study aims to determine the effect of phenotype and cortisol on anxiety status in polycystic ovary syndrome (PCOS) patients. Methods: 40 patients diagnosed with polycystic ovary syndrome (PCOS) aged 18-40 years in Makassar. The Indonesian version of the Hamilton Anxiety Rating Scale (HAM-A) assesses anxiety. A blood sample is taken to check for cortisol (drip blood test). Cortisol levels were measured using the CMIA (Chemiluminescent microparticle Immunoassay) method. Data were analyzed using SPSS version 25.0 for Windows. Results: The prevalence of phenotypes A, B, C, and D were 27.5%, 0%, 45%, and 45%, respectively. Phenotype C had a higher body mass index than the other phenotypes but was not significantly different. (p &gt; 0.05). About 26.1% of patients with phenotype A were found to suffer from mild anxiety and 29.5% experienced moderate anxiety. Compared to phenotype C, 52.2% experienced mild anxiety and 35.5% experienced moderate anxiety; however, these results were not statistically significant. Higher cortisol levels were found in phenotype A compared to other phenotypes (phenotype C; 7.01±3.12 and phenotype D; 6.37±3.02) but not significantly different (p&gt;0.05). Conclusion: The PCOS phenotype has no relationship with the anxiety status of PCOS patients and there is no relationship between the phenotype and serum cortisol levels in PCOS patients.

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.

THU645 Comparison Of LC-MS/MS Testosterone Assays Towards Standardization Of Lower Testosterone Ranges

Abstract Disclosure: M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Eli-Lilly, Amino Co. S. Ottey: None. K.D. Sherif: None. O. Sugahara: None. F. Pokuah: None. A.N. Lyle: None. V. Hubert: None. Objective: Polycystic ovary syndrome (PCOS) is a common disorder in women. The diagnosis of PCOS often includes elevated concentrations of serum testosterone. Previous work has harmonized the higher range of the testosterone assay and normative cut-offs for low and high testosterone concentrations for the male gender. However, similar work is needed to better align existing Liquid Chromatography Tandem Mass Spectroscopy (LC-MS/MS) methods in the lower range of testosterone and determine upper limits of normal for females. Methods: This is a secondary analysis of a pooled cohort of 60 obese adolescents with and without PCOS, enrolled in 1 of three studies (NCT02157974; NCT03041129; NCT03717935) at the University of Colorado, Anschutz. None of the participants were taking hormonal medication to treat PCOS. Frozen plasma samples collected between 6-7 AM were analyzed by Esoterix hormone branch of LabCorp (Agoura Hills, CA) and by the Centers for Disease Control (CDC) Clinical Standardization Programs with LC-MS/MS. Samples were selected from the available participants to encompass the full range of testosterone concentrations available within the cohort. Results: Within the entire cohort (N=60, Age = 15.8, SD: ± 1.7 years, BMI 35.4, SD: ± 5.5 kg/m2), the means between the assays were statistically, but not clinically different (CDC 48.4 SD: ±24.4 ng/dL vs OL 45.4 SD: ±22.1, p=0.013).Deming regression indicated that the assays were not different with an intercept of 2.05 (-3.69 to 7.79, 95% confidence interval) and slope of 0.895 (0.753 to 1.04, 95% confidence interval). The two assays were highly correlated via linear regression (R2=0.859, p&amp;lt;0.001) and with a Bland-Altman comparison, the CDC assay only had a slight positive bias of 3.04, SD: ± 9.18 ng/dL relative to Esoterix. When divided by PCOS status (PCOS N=52, Hirsutism score 6.5±5.9, Control N=8, Hirsutism score 2.1±4.5), the CDC assay ROC demonstrated discrimination of PCOS status with an AUC of 0.903 (0.800-1.00), p&amp;lt;0.001 and the Youden index was &amp;lt;27.1 ng/dL with a sensitivity of 87.5% and a specificity of 86.5%. However, when the sensitivity was at 100%, the specificity was 57.7% and the cut-off &amp;lt;43.0 ng/dL. Conclusions: The Esoterix, a major commercial lab, assay is very similar to that of CDC LC-MS/MS, and able to discriminate PCOS status at 43.0 ng/dL. Future work is needed to 1) align more clinical assays to the CDC standard and 2) define a common cut-off to describe hyperandrogenism in females across the weight and age spectrum. Presentation: Thursday, June 15, 2023

THU632 Musculoskeletal Composition And Function In Polycystic Ovary Syndrome: Early Evidence From A Prospective Study

Abstract Disclosure: M. Kazemi: None. J. Michalak: None. I.B. Xavier: None. S.A. Parry: None. M.E. Lujan: None. Current evidence on the body composition of women with polycystic ovary syndrome (PCOS) is primarily focused on fat accumulation and impaired fat function. The relevance of PCOS to non-fat (skeletal muscle, bone) components of body composition remains unknown, despite the clinical and prognostic value for musculoskeletal function and healthy aging. We recently showed a link between PCOS and the loss of skeletal muscle mass and bone concurrent with fat infiltration. While our observations reflect an aberrant musculoskeletal composition in PCOS, any impact on function is unknown. The objective of the current study was to test the hypothesis that musculoskeletal function and composition are poorer in PCOS vs. controls without PCOS. This work represented early evidence from a prospective case-control study (N=25, age 18-35y; BMI 18.2-41.5 kg/m2). Cases were defined as those with PCOS (NIH criteria; n=12). Controls were those without PCOS (n=13). Musculoskeletal composition traits (bone mineral density [BMD], lean body mass [LBM]) were evaluated by dual-energy X-ray absorptiometry. Furthermore, musculoskeletal function traits (maximum and average isometric strength of the hand and forearm muscles in 3 trials) were evaluated with a hydraulic dynamometer. Associations between PCOS status and traits were evaluated using generalized linear regression models. All p-values were BMI adjusted. Analyses of the musculoskeletal composition traits revealed comparable BMD between PCOS cases and controls (mean [SD]: 1.13 [0.03] vs. 1.11 [0.02] g/cm2; P=0.30). In contrast, PCOS cases showed an association with lower LBM vs. controls (40.98 [26.71] vs. 43.86 [24.10] kg; P&amp;lt;0.001). Regarding musculoskeletal function, PCOS cases showed an association with lower maximum (29.10 [1.89] vs. 34.46 [1.88] kg; P=0.007) and average (27.33 [1.84] vs. 32.35 [1.88] kg; P=0.008) isometric strength of the dominant hand vs. controls. Similarly, PCOS cases showed an association with lower maximum (28.10 [2.15] vs. 32.25 [1.69] kg; P&amp;lt;0.001) and average (26.93 [2.04] vs. 30.42 [1.61] kg; P&amp;lt;0.001) isometric strength of the non-dominant hand vs. controls. Quantitative musculoskeletal traits, including lower LBM and hand grip strength differ in PCOS vs. controls. These findings reflect poorer skeletal muscle mass, physical fitness, and overall health status in PCOS. If confirmed by longitudinal studies, these observations may translate to a greater risk for musculoskeletal derangements in later life stages. Potential mechanisms underlying these aberrations are being investigated and will likely reveal environmental and biological pathways (assuming interactive) beyond obesity per se. Future studies should also delineate causal pathways of PCOS to musculoskeletal aberrations. Presentation: Thursday, June 15, 2023

FRI417 An Interdisciplinary Program Promoting The Adoption Of A Healthy Lifestyle Increases Insulin Sensitivity In Women With Obesity And Infertility

Abstract Disclosure: A. Forget-Renaud: None. M. Belan: None. F. Jean-Denis: None. M. Pesant: None. J. Baillargeon: Grant Recipient; Self; Ferring Pharmaceuticals, JPB received an unrestricted investigator-initiated grant from Ferring Canada, which was not for the reported study. Introduction Obesity increases the risk of ovulatory and anovulatory infertility in women, mainly through the development of polycystic ovary syndrome (PCOS). Insulin resistance contributes to the pathogenesis of PCOS and may play a role in the infertility of PCOS and non-PCOS women with overweight or obesity. Lifestyle modifications are recommended as a first-line therapy in women with PCOS or those with obesity and infertility, as it was associated with improvement in menstrual pattern and fertility outcomes. We therefore hypothesized that a lifestyle intervention may increase insulin sensitivity in women with obesity and infertility. Methods Women with obesity and infertility were randomly allocated to usual fertility care (control group, CG) or to an interdisciplinary intervention promoting the adoption of a healthy lifestyle (LSG) alone for 6 months and then combined with usual care. Insulin resistance was estimated during fasting (HOMA-IR) and a 75-g oral glucose test (Matsuda Insulin Sensitivity Index, ISI(M)), and β-cell function was estimated using the Insulin Secretion-Sensitivity Index (ISSI-2) in women not taking medication affecting insulin sensitivity (except metformin). Data were collected at baseline, 6, 12 and 18 months, and as soon as possible when the participant knew she was pregnant. We estimated the integrated change in insulin sensitivity during follow-up using the incremental area-under-the-curve of ISI(M) divided by time (iAUC-ISI(M)/time). Results Among 130 randomized participants, 105 had available data (LSG=51, CG=54). PCOS was diagnosed using the Rotterdam criteria in 63.2% of participants, equally distributed between the groups. As compared to CG, women in the LSG improved significantly more their ISI(M) after 6 months (+0.24 [IQR: -0.48 - +0.94] vs 0.16 [-1.32 - +0.53], p=0.039, n=90), as well as their iAUC-ISI(M)/time during follow-up (+0.18±0.84 vs -0.21±0,93, p=0.035, n=104). All these results remained statistically significant after correction for baseline BMI, age and use of folic acid. Increases in iAUC-ISI(M)/time in the intervention vs control groups were significantly more important (p for interaction=0.045) in participants with baseline ISI(M) above the median (LSG: +0.10±1.13, n=24, vs CG: -0.62±1.13, n=27, p=0.028) than in those below the median (LSG: +0.26±0.48, n=27, vs CG: +0.21±0.35, n=26, p=0.71). Interactions with PCOS status and other subgroups were not statistically significant. There was no impact on HOMA-IR or ISSI-2. Conclusion An interdisciplinary program promoting the adoption of a healthy lifestyle significantly increases whole-body insulin sensitivity in women with infertility and obesity, mainly in those with higher baseline insulin sensitivity. It may be explained in part by the weight loss associated with the intervention and may have a role in improving fertility in this population. Presentation: Friday, June 16, 2023

SAT356 Predicting Nonalcoholic Fatty Liver Disease in Adolescent Girls with Polycystic Ovary Syndrome and Obesity

Abstract Disclosure: J.S. Lo: None. F. Bril: None. A. Taylor: None. N. Morelli: None. M.A. Ware: None. Y. Garcia-Reyes: None. M.J. McPhaul: Employee; Self; Quest Diagnostics. M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Amino Corp. Adolescents with obesity and polycystic ovary syndrome (PCOS) have significant insulin resistance and are at high risk of nonalcoholic fatty liver disease (NAFLD). This risk may be related to increased growth hormone and insulin resistance associated with puberty, in addition to excess testosterone. NAFLD is difficult to diagnose in obese individuals. Intact insulin (II), as measured by mass spectrometry, multiplied by alanine aminotransferase (ALT; II*ALT) has emerged as a strong predictor for NAFLD in adults (ROC 0.94 [0.89-0.99]). However, II*ALT has not been used in predict NAFLD in adolescents with PCOS. To assess the utility of II*ALT measurements in predicting NAFLD in the context of pubertal timing in a high-risk population of adolescents with PCOS and obesity. Participants were screened to confirm PCOS status per 2018 international guidelines. Liver fat fraction was measured with MRI Dixon, and fasting laboratory assessments were performed including traditional insulin (TI) and insulin growth factor-1 (IGF-1), measured with ELISA and ALT, AST. NAFLD was defined as a liver fat ≥5.0%. Mass spectrometry was used to measure intact molecules of II and C-peptide. Seventy-seven adolescent girls with PCOS and obesity who were Tanner 5 and at least 1-year post-menarche were enrolled (age 16.3 ± 1.7 years, BMI 34.9 ± 5.0 kg/m2). There was no difference in the prediction of NAFLD between II and TI (AUROC 0.72 [0.59-0.85] vs. 0.66 [0.53-0.79], p=0.39). Of note, the combination of II*ALT (ROC 0.83 [0.72-0.95], sensitivity 77%, specificity 65%) performed better in predicting NAFLD than II alone (ROC 0.72 [0.59-0.85]), ALT alone (ROC 0.81 [0.71-0.91]), and better than TI*ALT (ROC 0.75 [0.63-0.86]) for the entire cohort (p&amp;lt;0.01 for overall comparison). Patients were divided into 2 groups based on age as a surrogate for pubertal duration (Age &amp;lt;15: n=22, age 13.9 ± 0.8, BMI 32.7 ± 4.9 kg/m2, and Age &amp;gt;15: n=55, age 17.3 ± 0.9, BMI 35.8 ± 4.8 kg/m2). II*ALT had a higher ROC to predict NAFLD in the &amp;gt;15 group (ROC 0.90 [0.81-0.98], sensitivity 97%, specificity 60%) compared to the &amp;lt;15 group (ROC 0.71 [0.41-0.99] sensitivity 81%, specificity 83%), although it did not reach statistical significance. There was no effect of race and ethnicity on these relationships. The II*ALT index performs better than II and ALT alone for the detection of NAFLD and outperforms TI*ALT as well. It is a strong predictor for NAFLD in adolescents &amp;gt;15 years old with PCOS and obesity, with results very similar to those published in adults. However, it is not as robust in adolescents younger than 15 years old, perhaps due to the effect of pubertal hormones altering the relationship between liver fat and insulin concentrations. Presentation Date: Saturday, June 17, 2023