Virtual Reality-Based Exercise in Adolescents with Polycystic Ovarian Syndrome -Induced Fatty Liver: An Interesting and Entertaining Method Requiring More Attention

Abnormal aminotransferase activity in women with polycystic ovary syndrome

IL-22 and its interaction with amino acid and glycolipid metabolite in polycystic ovary syndrome (PCOS) patients

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

Objective To compare the prevalence of non-alcoholic fatty liver disease (NAFLD) in women with or without polycystic ovary syndrome (PCOS), and to evaluate association between PCOS and NAFLD. Methods A cross-sectional study was performed including 122 PCOS patients (PCOS group) and 107 age, and body mass index (BMI)-matched women (control group). Anthropometric parameters, liver enzyme, lipid profile, glucose and insulin levels, sex hormones and hepatic ultrasonography were measured in all subjects. The clinical features, laboratory parameters and prevalence of NAFLD were compared between PCOS group and control group. The related factors were evaluated between PCOS and NAFLD, finally the role of insulin resistance (IR) and hyperandrogenism (HA) was analysed. Results Women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (62.6% vs. 76.2%, P=0.025). Logistic regression found that HOMA-IR and FAI were associated with NAFLD in PCOS women (OR=1.686, 95% CI=1.279-2.223; OR=1.167, 95% CI=1.039-1.311), however, there was no significant correlation between FAI and NAFLD after adjustment for HOMA-IR (P>0.05). Conclusion NAFLD is more prevalent in women with PCOS than in those without. Insulin resistance and HA drive risk of NAFLD in young female with PCOS. IR may be an independent risk factor for NAFLD, and the association between HA and NAFLD is not independent but is mediated by IR. Key words: Polycystic ovary syndrome; Non-alcoholic fatty liver disease; Insulin resistance; Hyperandrogenism

Objective To explore the incidence of insulin resistance (IR) in patients with obese polycystic ovary syndrome (PCOS) and its relationship with body composition including body fat (BF) and visceral fat area (VFA). Methods In the period from April 2013 to December 2014, in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, 62 patients with obese PCOS who were in the weight loss program in the Department of Clinical Nutrition were selected, and 19 obesity subjects without PCOS, matching with the obsess PCOS group in age and body mass index (BMI), were selected as controls. In the cases and controls, we used Biospace Inbody720 body composition analyzer to determine their body composition, measured serum lipid profile, conducted 75 g oral glucose tolerance test and insulin release test, and calculated homeostasis model assessment of insulin resistance (HOMA-IR). Results Blood lipids, insulin level, and HOMA-IR were not significantly different between the obese PCOS and the control groups (all P>0.05). Both groups showed IR (defined as HOMA-IR≥2.69), and HOMA-IR in the obese PCOS group was higher than that in the control group, but with no significant difference(6.17 ± 3.15 vs. 5.00±2.18, t= 1.515, P= 0.134). The mean alanine aminotransferase (ALT) level in the obese PCOS group was higher than normal, and the ALT values and the proportion of patients with ALT> 40 U/L were higher than those in the control group, but with no significant difference (P= 0.106 and P= 0.134). Those with nonalcoholic fatty liver disease (NAFLD) accounted for 27/62 in the obese PCOS group, also higher than the 6/19 in the control group(χ2 = 0.863, P= 0.353). BF in the obese PCOS group was lower than that in the control group [(36.28±6.16)kg vs. (39.56±6.13)kg, t=-2.032, P=0.046], so was VFA after adjusting for waist-to-hip ratio [(150.39±22.86)cm2vs. (161.74±20.77)cm2,OR=0.963, P=0.040]. Linear regression analysis showed that HOMA-IR was not correlated with BF, VFA or other body composition indexes in the obese PCOS patients (all P>0.05). Conclusions Obesity PCOS patients have significant IR, but HOMA-IR seems to be not correlated with BF, VFA, and other body composition indexes in this population. Studies with larger sample size and exploring relevant mechanisms are still needed. Key words: Obesity; Polycystic ovary syndrome; Insulin resistance index; Inbody720 body composition analyzer; Visceral fat area

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition characterized by endocrine, reproductive and metabolic abnormalities. There is no cure for PCOS and existing treatments are suboptimal. Obesity and adverse metabolic features are prevalent in PCOS patients, but weight loss has a beneficial effect on PCOS features. However, dietary interventions aimed at weight loss are difficult to sustain long-term. Interestingly, recent data from animal studies has shown that a mitochondrial uncoupler, BAM15, is an effective approach to pharmacologically treat obesity and metabolic diseases. Aim: To investigate the efficacy of BAM15 to ameliorate PCOS-traits in a PCOS mouse model. Method: The effect of BAM15 treatment on metabolic and reproductive PCOS features were evaluated in dihydrotestosterone (DHT)-induced PCOS mice fed a standard chow diet ± BAM15 for 10 weeks. Results: As expected, exposure of female mice to DHT induced the PCOS metabolic features of increased body weight (P<0.05), lean mass (P<0.001), increased parametrial and mesenteric fat pad weights (P<0.05) and adipocyte hypertrophy (P<0.05). DHT-induced PCOS mice also exhibited increased HOMA-IR, cholesterol and fasting triglyceride levels and hepatic steatosis (all P<0.05). Conversely, DHT-induced PCOS females treated with BAM15 displayed lowered body weights similar with controls, a significant decrease in parametrial and mesenteric fat depot weights (P<0.05) and reduced adipocyte hypertrophy. Likewise, BAM15 treatment decreased HOMA-IR, cholesterol and fasting triglyceride levels and the degree of hepatic steatosis observed in PCOS females, to levels comparable with control females. Lastly, PCOS mice presented the reproductive PCOS traits of irregular cycles and ovulatory dysfunction, though BAM15 treatment did not improve these PCOS features. Conclusion: These findings demonstrate that the pharmacologic mitochondrial uncoupler BAM15 is able to ameliorate metabolic PCOS features in a PCOS mouse model. These data provide evidence to support BAM15 as a potential innovative therapeutic approach to manage associated metabolic PCOS features.

Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients. To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort. This was a case-control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS. Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P=0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25-5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status. Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.

Disclosure: S. Zhang: None. J.A. Darbinian: None. L.C. Greenspan: None. J.B. Schwimmer: Grant Recipient; Self; Intercept, Seraphina. J.C. Lo: None. Background: We recently observed that US Asian/Pacific Islander (PI) adolescents have two-fold higher odds of polycystic ovary syndrome (PCOS) compared to non-Hispanic White adolescents, with prevalence strongly associated with higher BMI. Moreover, similar to Hispanic/Latina adolescents, Asian/PI adolescents with obesity have much higher odds of elevated alanine aminotransferase (ALT), a biochemical marker for suspected non-alcoholic fatty liver disease (NAFLD). In a pilot study, we observed that PCOS was an independent predictor of elevated ALT in adolescent females with obesity. In this study, we characterized the association of PCOS and elevated ALT in a much larger population of adolescent females and further examined the burden of elevated ALT within the PCOS subset. Methods: We used data from 15,683 females aged 13-17 years who were members of a US integrated healthcare system, had a well-child visit in 2012-2018, met BMI criteria for obesity (BMI ≥95th percentile), and had ALT measured within 1 year of the visit. Elevated ALT was defined as ≥44 U/L (NASPHGAN criteria). PCOS was identified based on clinical diagnosis within 1 year of the visit. Class I, II, III obesity were defined by BMI percent of the 95th percentile from 100 to <120%, 120% to <140%, and ≥140%, respectively. Differences between PCOS and non-PCOS groups were compared using the Chi-square test. Multivariable logistic regression was used to examine the association of PCOS and elevated ALT. Results: Among 15,683 adolescent females with obesity and measured ALT (23.5% White, 14.1% Black, 11.0% Asian/PI, 46.8% Hispanic, and 4.7% other/unknown race and ethnicity), 5.5% had diagnosed PCOS and 39.5% had severe (class II-III) obesity. The prevalence of elevated ALT was 5.1% overall and was substantially higher among those with PCOS (10.6%) compared to those without PCOS (4.7%, p<0.001). In multivariable analyses, PCOS was associated with a 1.8-fold (CI 1.4-2.2) higher odds of elevated ALT, adjusting for age, race/ethnicity, and level of obesity. Similar to our prior report, greater obesity severity, Asian/PI race, and Hispanic ethnicity were significant predictors of elevated ALT. Among the subset of 865 adolescents with obesity and PCOS (40.9% class I, 34.9% class II, 24.2% class III obesity), the prevalence of elevated ALT varied by race and ethnicity, ranging from 15.8% among Asian/PI, 12.8% among Hispanic/Latina, 8.5% among White, and 2.0% among Black females. Conclusion: Our findings confirm a strong independent association of PCOS and elevated ALT among adolescent females with obesity. Among those with both obesity and PCOS, about 1 in 10 had elevated ALT, increasing to 1 in 8 among Hispanic/Latina females and nearly 1 in 6 among Asian/PI females. These findings support recommendations for NAFLD screening in adolescents with PCOS and consideration of screening in young adult women with PCOS, especially high-risk subsets. Presentation: Saturday, June 17, 2023

Polycystic ovary syndrome (PCOS) increases non-alcoholic fatty liver disease (NAFLD) risk and severity in adults, but data in adolescents with diverse backgrounds are limited. We evaluated NAFLD prevalence and characterized NAFLD risk factors in overweight/obese adolescents by PCOS status. Retrospective study of overweight (n=52)/obese (n=271) female adolescents (12-18 years old), evaluated clinically 2012-2020, was conducted comparing PCOS patients to age-matched non-PCOS controls. NAFLD was defined as ALT≥44U/L x2 and/or≥80U/L x1, hepatic steatosis on imaging, or NAFLD on biopsy, in absence of other liver disease. Metabolic comorbidities were captured. Log-binomial regression models estimated prevalence risk ratios (PR). NAFLD prevalence was 19.1% in adolescents with PCOS (n=161), similar to those without (n=162) (16.8%, p=0.6). Adolescents with PCOS were more likely to have insulin resistance, hypercholesterolemia, and higher triglycerides (p<0.05). Those with PCOS and concomitant type 2 diabetes (T2DM) did have increased NAFLD risk (PR 2.5, p=0.04), but those with PCOS without T2DM did not (PR 0.9, p=0.8). Adolescents with PCOS and NAFLD, compared to those with PCOS without NAFLD, had a higher prevalence of metabolic comorbidities including hypercholesterolemia (77 vs. 48 %), T2DM (29 vs. 8 %), and hypertriglyceridemia (65 vs. 37 %) (p<0.01). Almost 1 in 5 overweight/obese female adolescents had NAFLD, but PCOS did not increase NAFLD risk in this diverse cohort. Among young women with PCOS, concomitant T2DM did increase the risk for NAFLD. Closer monitoring of obesity comorbidities in adolescents with PCOS is essential for optimizing health and merits updating current guidelines.

Introduction:Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women in reproductive age that is associated with insulin resistance (IR) and metabolic abnormalities which are also a part of metabolic syndrome (Met S). This study was aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) women diagnosed with PCOS based on the Rotterdam criteria from January 2013 to June 2014.Methods:In this cross-sectional study, 75 women with PCOS and 75 healthy controls were enrolled. Anthropometric parameters, biochemical and hormonal investigation, were measured in all women. IR was calculated by homeostasis model assessment. Abdominal ultrasonography and biochemical tests were used to determine the NAFLD.Results:The level of triglyceride, cholesterol, low-density lipoprotein, aspartate aminotransferase, alkalin phosphatase, fasting insulin, and homeostatic model assessment index in women with PCOS were significantly higher than women without PCOS. High-density lipoprotein and alanine aminotransferase (ALT) in women with PCOS were significantly lower. The frequency of IR women with or without PCOS was 53.3% and 29.3%, respectively (P = 0.003). The frequency of Met S in women with PCOS was 33.3% and in other was 10.7% (P = 0.001). The prevalence of fatty liver in women with or without PCOS was 38.7% and 18.7%, respectively (0.008). In women with PCOS, body mass index (BMI) (odds ratio [OR] = 4.25; P = 0.046), ALT (OR = 1.62; P = 0.005), fasting insulin (OR = 1.32; P = 0.032), and IR (OR = 58.17; P = 0.025) were associated with a higher fatty liver.Conclusions:NAFLD is frequent in patients with PCOS with combination with other metabolic derangements. BMI, ALT, fasting insulin, and IR are the risk factors for high prevalence of NAFLD in women with PCOS.

Polycystic ovary syndrome (PCOS) is a common disorder for women of child-bearing age and is associated with metabolic syndrome (MS). To assess the literature for associations between polycystic ovary syndrome and non-alcoholic fatty liver disease (NAFLD). We performed a systematic review using PubMed-search for peer-reviewed articles related to polycystic ovary syndrome and NAFLD. Articles were summarised and grouped according to different sections defining interactions of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease as well as risk factors, pathogenic pathways and treatment options. Obesity is a common factor involved in both polycystic ovary syndrome and non-alcoholic fatty liver disease. Obesity causes non-alcoholic fatty liver disease and aggravates hirsutism and menstrual disorders in polycystic ovary syndrome. Insulin resistance, a hallmark of metabolic syndrome is observed in 50-80% of women with polycystic ovary syndrome and patients with non-alcoholic fatty liver disease. Recent findings suggest that women with polycystic ovary syndrome may be at risk for developing non-alcoholic fatty liver disease and conversely, non-alcoholic fatty liver disease may be a risk for polycystic ovary syndrome. Based on the association of polycystic ovary syndrome and other metabolic abnormalities, such as insulin resistance, hyperandrogenism, obesity and non-alcoholic fatty liver disease, the candidate genes have been speculated for polycystic ovary syndrome. Closer scrutiny of these genes placed most of their proteins at the crossroads of three highly inter-related conditions: metabolic syndrome, obesity and non-alcoholic fatty liver disease. In most studies, the prevalence of both polycystic ovary syndrome and non-alcoholic fatty liver disease rises proportionally to the degree of insulin resistance and increases in the mass of adipose tissue. Non-alcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Similarly, it seems appropriate to consider polycystic ovary syndrome as the ovarian manifestation of metabolic syndrome. Both these conditions can co-exist and may respond to similar therapeutic strategies.

BackgroundPhysical exercise (PE), virtual reality-based exercise (VRE), and brain exercise (BE) can influence physical and cognitive conditions in older persons. However, it is not known which of the three types of exercises provide the best effects on physical and cognitive status, and which exercise is preferred by older persons. This study compared the effects of PE, VRE, and BE on balance, muscle strength, cognition, and fall concern. In addition, exercise effort perception and contentment in older persons was evaluated.MethodsEighty-four older persons (n = 84) were randomly selected for PE, VRE, BE, and control groups. The exercise groups received 8-week training, whereas the control group did not. Balance was assessed by Berg Balance Scale (BBS) and Timed Up and Go test (TUG), muscle strength by 5 Times Sit to Stand (5TSTS) and left and right hand grip strength (HGS), cognition by Montreal Cognitive Assessment (MoCA) and Timed Up and Go test Cognition (TUG-cog), fall concern by Fall Efficacy Scale International (FES-I), exercise effort perception by Borg category ratio scale (Borg CR-10), and exercise contentment by a questionnaire.ResultsAfter exercise, PE significantly enhanced TUG and 5TSTS to a greater extent than VRE (TUG; p = 0.004, 5TSTS; p = 0.027) and BE (TUG; p = 0,012, 5TSTS; p < 0.001). VRE significantly improved MoCA (p < 0.001) and FES-I (p = 0.036) compared to PE, and 5TSTS (p < 0.001) and FES-I (p = 0.011) were improved relative to BE. MoCA was significantly enhanced by BE compared to PE (p < 0.001) and both MoCA and TUG-cog were improved compared to VRE (p = 0.04). PE and VRE significantly (p < 0.001) increased Borg CR-10 in all exercise sessions, whereas BE showed a significant improvement (p < 0.001) in the first 4 sessions. Participants had a significantly greater satisfaction with BE than controls (p = 0.006), and enjoyed VRE and BE more than PE (p < 0.001). Subjects in all exercise groups exhibited benefits compared to the control group (p < 0.001).ConclusionsPE provided the best results in physical tests, VRE produced measurable improvements in physical and cognition scores, while BE enhanced cognition ability in older persons. Older persons preferred VRE and BE compared to PE. Both exercises are suggested to older persons to improve physical and cognitive conditions.

Do women with PCOS have a unique predisposition to obesity?

Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD). Retrospective study of women ages 18-45years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status. Among 102 women meeting study criteria, 36% (n=37) had PCOS; median age was 35years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102mg/dL, P=.05) and body mass index(BMI) (38 vs 33kg/cm2 , P<.01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P=.3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P=.02), presence of any fibrosis (84% vs 66%, P=.06) and advanced fibrosis (16% vs 6%, P=.10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1-10.6, P=.03) and advanced fibrosis (OR 7.1, 95% CI 1.3-39, P=.02). Among women with advanced fibrosis, median age was 5years younger in those with as compared to those without PCOS (40 vs 45years, P=.02). Polycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.

The aim of this study was to determine if there is an association between non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS). NAFLD and PCOS are both known to be associated with metabolic syndrome/insulin resistance. Fourteen consecutive female patients of reproductive age (20-45) either with liver biopsy proven NAFLD (50%) or abdominal ultrasound (US) consistent with steatosis together with elevated ALT levels (50%) were screened for PCOS using 2003 Rotterdam consensus meeting criteria. Other causes of hyperandrogenism were excluded. All subjects underwent relevant questionnaire and clinical exam together with hormonal assays, pelvic (1) or transvaginal US (13) and were screened for evidence of the metabolic syndrome. Ten out of fourteen women matched 2003 Rotterdam consensus meeting diagnostic criteria for PCOS (71%). Eight women suffered from oligo/amenorrhoea, nine women manifested presence of hyperandrogenism and six had history of infertility. Seven women had evidence of biochemical hyperandrogenism with low SHBG, raised free testosterone and elevation of serum LH concentration. Seven women fulfilled US criteria for PCOS. Three of ten patients with PCOS also had type 2 diabetes mellitus. Women with PCOS and NAFLD had higher triglyceride and cholesterol and lower HDL level than group without PCOS. Five patients with NAFLD and PCOS had documented fibrosis on liver biopsy, indicative of more advanced liver disease. Despite limitations of the study due to the sample size, we found evidence of PCOS in the majority of subjects with NAFLD. Women with NAFLD should be routinely screened for presence of PCOS, diabetes mellitus and metabolic risk factors for cardiovascular disease. Equally, women with PCOS should be screened for NAFLD. Evaluation for liver disease should be considered at an earlier age in some women with PCOS particularly those with an evidence of metabolic syndrome.