Polycystic Ovary Syndrome Subgroups Research Articles

MALAT1 expression in granulosa cells in PCOS patients with different phenotypes

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept.

Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis. Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G. Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans. LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.

Enhancement of Melanocortin-4 Receptor (MC4R) and Constancy of Kiss1 mRNAs Expression in the Hypothalamic Arcuate Nucleus in a Model of Polycystic Ovary Syndrome Rat

Background: Hypothalamic Melanocortin-4 Receptor (MC4R) and kiss1/kisspeptin systems play roles in reproductive processes. This study was conducted to evaluate changes in MC4R and kiss1 genes expression in the arcuate nucleus (ARC) of the hypothalamus and its relationship with polycystic ovary syndrome (PCOS) in rats. Materials and Methods: In the current experimental study, 24 female rats were randomly and equally allocated into nulliparous and primiparous groups and then were divided into two subgroups of PCOS and control. PCOS was induced by exposure to continuous light. Sex-related hormones were evaluated by radioimmunoassay or immunoradiometric assay. Expressions of MC4R and kiss1 gene in the ARC of the hypothalamus of the rats were evaluated by real-time PCR. Histomorphometric alterations of ovaries were compared between groups. Results: Number of tertiary follicles and their size and number of atretic follicles in the PCOS subgroups were more than those in the controls (P&lt;0.05) whereas the number of secondary follicles and corpus luteum in the PCOS subgroups were lower than those in the controls (P&lt;0.05). Antrum and total diameters of tertiary follicles in the PCOS subgroups were greater and granulosa layer diameter was lower than those in the controls (P&lt;0.05). The MC4R mRNA expression in the PCOS subgroups was 6.5-fold in nulliparous and 3.5-fold in primiparous groups more than their controls’ pairs (P&lt;0.05). However, parity did not affect the expression of MC4R gene (P&gt;0.05).The kiss1 mRNA expression in the PCOS and control subgroups was not significantly different (P&gt;0.05). Conclusion: Overexpression of MC4R gene after PCOS induction in the ARC of the hypothalamus may link to metabolic disorders of induced PCOS in the rats. However, alteration in the kiss1 mRNA expression after PCOS induction was not observed in the rats. [GMJ.2018;7:e1070]

Altered Vitamin D Status and Bone Mineral Density in Obese and Non-obese Patients With Polycystic Ovary Syndrome: A Cross-Sectional Study in Turkey.

Background Polycystic ovary syndrome (PCOS) is the most common endocrinological disease in women of reproductive age. In addition to providing the basis for comorbidities such as metabolic and cardiovascular diseases, it also affects bone metabolism. This study aimed to determine whether there is a relationship between bone mineral density (BMD), vitamin D status, insulin resistance, sex hormones, and calcium metabolism disorders in women with PCOS. Methodology Fifty-six non-obese women with PCOS, 67 obese women with PCOS, and 45 normal weight controls participated in the study. Circulating levels of gonadotropins, estradiol, prolactin, dehydroepiandrosterone sulfate, total testosterone, thyroid stimulating hormone, sex hormone-binding globulin, insulin, glucose, and calcium metabolism parameters were assessed. We used the Homeostatic Model Assessment-Insulin Resistance Index to detect insulin resistance. BMD values in the various body regions were measured by dual X-ray absorptiometry. Results Women with PCOS had significantly lower vitamin D values and lumbar spine BMD than controls (p <0.001 and p <0.05, respectively). Among the patients with PCOS subgroups, vitamin D deficiency (VDD) was more frequent in obese PCOS patients (67.1%) than in non-obese patients (58.9%). We found significantly lower BMD at all sites only in the subgroup of the non-obese PCOS women than in controls (p <0.001). Conclusions VDD is prevalent in PCOS women in those with obesity and hyperandrogenemia. Non-obese PCOS women have significantly lower BMD measurements than healthy controls, but obese PCOS women have BMD values comparable with normal-weight eumenorrheic controls. Body mass index is the most important factor determining BMD in women with PCOS.

The presence of polycystic ovary syndrome increases the risk of maternal but not neonatal complications in women with type 2 diabetes in pregnancy.

Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain (unadjusted 12.0 vs. 11.4kg, adjusted mean difference 2.1kg [0.3, 3.9], p=0.021) and higher total insulin dose at 34-36weeks (unadjusted 172 vs. 124 units per day, adjusted mean difference 44 units [15, 73], p=0.004), but no difference was seen in neonatal outcomes. Unlike the non-PCOS subgroup, metformin treatment versus placebo in the PCOS subgroup was associated with an increase in extremely large-for-gestational-age infants (28.6 vs. 14.0%, p=0.008 for interaction) and an increase in worsened pre-existing maternal hypertension (16.7 vs. 4.5%, p=0.046 for interaction). Clinicians should be alerted to the potential for high insulin requirements and excess weight gain in pregnant patients with T2DM and comorbid PCOS. Moreover, metformin may not be as beneficial in this population as previously understood.

Marrow adipose tissue is increased in overweight and obese women with PCOS independently of hyperandrogenism related obesity and metabolic disorders.

This study aimed to investigate the increase in bone marrow adipose tissue (BMAT) in overweight and obese women with polycystic ovary syndrome (PCOS) and its relationship with hyperandrogenism, obesity, and metabolic disorders. The study included 87 overweight or obese women with PCOS (mean age 29 ± 4 years), as well as 87 age-matched controls recruited from a separate population study. All PCOS patients were measured for anthropometric features, abdominal adipose tissue areas, BMAT, biochemistry, and sex hormones. BMAT was compared between the PCOS patients and controls. In PCOS patients, subgroup comparisons of BMAT and its associations with body adiposity indices, biochemistry, and sex hormones were analyzed. The odds ratios (ORs) of elevated BMAT (defined as BMAT ≥ 38%) were calculated. On average BMAT was increased by 5.6% ( ± 11.3%) in PCOS patients compared to controls. BMAT were significantly higher in the upper tertiles of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). BMAT was not correlated with abdominal adiposity indices or biochemistry except for LDL-C (r = 0.253-0.263, p = 0.014-0.018). LDL-C was not significantly different between the normal and abnormal androgen PCOS subgroups (p = 0.10-0.887). LDL-C, follicle stimulating hormone (FSH), and total testosterone (TT) were risk factors for elevated BMAT, with ORs of 1.899 (p = 0.038-0.040), 1.369 (p = 0.030-0.042), and 1.002 (p = 0.040-0.044) for each unit increase, respectively. BMAT was increased in overweight and obese PCOS patients, but the increase in BMAT was not associated with the hyperandrogenism related obesity or metabolic disorders.

The Relationship between Macronutrient Intake and Insulin Resistance in Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. It is linked to genetic and environmental factors such as nutrition. Insulin resistance (IR) is one of the major pathological changes in PCOS. This study aimed to determine the relationship between IR and macronutrient intake in PCOS subgroups.&#x0D; Methods: This case-control study was performed on 151 women with PCOS and were divided into four groups according to the Rotterdam diagnostic criteria: A=41, B=33, C=40, and D=37, and 31 women were also in the control group and did not have this syndrome. All macronutrients were assessed with a 168-item food frequency questionnaire (FFQ).&#x0D; Results: There was a significant relationship between HOMA-IR and some dietary components (Increased calorie in group A, increased total fat intake in group C, lower intake of unsaturated fats (PUFA and MUFA) in group D and higher intake of saturated fat (SFA) and protein intake in the control group). There was no correlation in subgroup B (ovulatory phenotype).&#x0D; Conclusion: Due to the significant relationship between IR and some dietary components in PCOS subtypes, it is recommended to maintain a balance in carbohydrate and fatty acids intake, and increase dietary fiber to improve health parameters in PCOS subjects.

Anti-Mullerian Hormone-Based Phenotyping Identifies Subgroups of Women with Polycystic Ovary Syndrome with Differing Clinical and Biochemical Characteristics.

Even though polycystic ovary syndrome (PCOS) was originally defined as "amenorrhea associated with bilateral polycystic ovaries", women without PCO morphology can be included in this diagnosis. This may contribute to the clinical heterogeneity seen in PCOS. Serum anti-Mullerian hormone (AMH) correlates with the number of ovarian cysts. We investigated whether phenotyping based on serum AMH can distinguish subgroups of PCOS with different clinical and biochemical characteristics. The electronic medical records of 108 women with PCOS (Rotterdam criteria) were reviewed. The serum AMH value correlated inversely (0.03 < p < 0.0001) with age, weight, and BMI values and directly with serum total testosterone (T), free T, and bioavailable T values. When divided into quartiles based on serum AMH values, the women in the highest quartile (AMH: 18.5 ± 9.9 ng/mL; n = 27) had lower BMI (29.4 ± 6.9 vs. 34.0 ± 10.6-36.7 ± 7.2 kg/m2) but higher total T (51.3 ± 27.2 vs. 26.5 ± 10.4-35.1 ± 16.3 ng/dL), free T (7.7 ± 6.0 vs. 4.4 ± 2.3-5.7 ± 3.2 ng/dL), and bioavailable T (22.1 ± 17.0 vs. 12.2 ± 6.6-16.5 ± 8.7 ng/dL) values. The combination of high AMH and high testosterone values may point to the ovaries and reproductive etiology for PCOS in this subgroup. Thus, AMH-based phenotyping may provide a practical and cost-effective tool to explore the heterogeneity in PCOS.

The Relationship between Insulin Resistance and Micronutrient Intake in Polycystic Ovary Syndrome Subgroups

Background: Polycystic ovary syndrome (PCOS) is with oxidative stress in women of reproductive age. Oxidative stress is an important factor in the development of insulin resistance. Some micronutrients are also linked to oxidative stress. The aim of this study was to determine the relationship between insulin resistance and micronutrient intake in PCOS subgroups. Methods: This case-control study was performed on 151 PCOS. They were divided into four groups according to the Rotterdam diagnostic criteria: D = 37, C = 40, B = 33, A = 41 and 31 women were also in the control group and did not have this syndrome. Micronutrient food intake was assessed with a 168-item FFQ feed frequency questionnaire. Insulin resistance was diagnosed with HOMA-IR index (Cut off&gt; 2.5). The data were analyzed with SPSS 22 using Kruskal Wallis (KW), Spearman, and Chi-square tests. Results: The mean age of participants was 28.53 years. There was a significant relationship between the HOMA-IR and some dietary components (selenium depletion in group A, zinc depletion, vitamin D, and vitamin E in group D, and vitamin D and vitamin E depletion in control group) (P &lt; 0.05). There was no relationship between subgroups B and C. Conclusion: Due to the significant relationship between insulin resistance indices, increasing the dietary intake of zinc, selenium, vitamin D, and vitamin E in women with PCOS, as well as increasing the dietary intake of these micronutrients in improving the physical health and fertility parameters of these people is recommended.

OR15-4 Heterogeneity of Clinical Presentation of Adolescent PCOS Is Attributable to Distinct Subtypes

Abstract Objective Adolescent polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome characterized by hyperandrogenism and irregular menses. Heterogeneous features of the syndrome include the presence/absence of obesity, degree of insulin resistance, and clinical and/or biochemical hyperandrogenism. In adult women with PCOS, discrete metabolic and reproductive subgroups can be identified. A recent study described distinct phenotypes using unsupervised hierarchical cluster analysis: a metabolic subgroup characterized by higher BMI, glucose, and insulin levels, and a reproductive subgroup demonstrating higher LH and SHBG levels. We hypothesized that non-obese and obese adolescent girls with PCOS would exhibit similar distinct phenotypes at the time of diagnosis. Methods Data were extracted from a multi-site PCOS registry including seven academic centers in the US with the following inclusion criteria: PCOS confirmed per 2018 international guidelines, diagnosis before age 18 years, and at least one follow-up visit. Data collected included demographics, medical and family history, physical characteristics including hirsutism, acanthosis nigricans, and laboratory measures such as HbA1c, ALT, lipid profiles and reproductive hormones (androgens, LH, FSH, SHBG). Hormone levels were normalized to the upper limit provided by the measuring laboratory. Patients were divided by obesity status, defined as obese (OB) with BMI ≥ 95th percentile for age and sex and non-obese (NO) &amp;lt; 85th percentile for age and sex. Differences in continuous variables were assessed with unpaired t-tests using GraphPad Prism. Results Complete diagnostic data from 390 patients from 7 different sites were included for analysis, with 284 OB (Age 15.3±1.5 years, BMI 36.1±5.6 kg/m2) and 68 NO (Age 15.8±1.3 years, BMI 22.6±3.4 kg/m2). OB presented with more severe acanthosis (p&amp;lt;0.0001) and higher HbA1c (OB 5.5±0.5, NO 5.2±0.3; %, p&amp;lt;0.0001), ALT (OB 35±30, NO 22±17; IU/L, p=0.0006), and triglycerides (OB 145±90, NO 110,±88; mg/dL, p=0.002). OB also presented with higher free testosterone (OB 219±188% vs NO 158±125% above upper limit of normal; p=0.003), while NO presented with higher total testosterone (OB 121±68%, NO 152±88% above upper limit of normal; p=0.003), androstenedione (OB 87±37%, NO 125±62 above upper limit of normal; p=0.002), and LH (OB 9.7±4.9, NO 15.2±10.4; mIU/mL, p=0.0001). No differences in Ferriman Gallwey score or number of menses in the 6 months prior to diagnosis were detected. Conclusions Metabolic and reproductive phenotypes differed in OB and NO adolescent girls at the time of PCOS diagnosis. The reproductive phenotype in NO was characterized by increased LH, total testosterone and androstenedione levels. In contrast, OB girls had a phenotype characterized by insulin resistance-driven hyperandrogenemia established by lower SHBG and higher free testosterone levels. Our data are consistent with findings reported for adult women with two divergent phenotypes: an insulin resistance-driven metabolic subtype and a primarily reproductive subtype, potentially driven by neuroendocrine mechanisms. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

Derailed peripheral circadian genes in polycystic ovary syndrome patients alters peripheral conversion of androgens synthesis.

Do circadian genes exhibit an altered profile in peripheral blood mononuclear cells (PBMCs) of polycystic ovary syndrome (PCOS) patients and do they have a potential role in androgen excess? Our findings revealed that an impaired circadian clock could hamper the regulation of peripheral steroid metabolism in PCOS women. PCOS patients exhibit features of metabolic syndrome. Circadian rhythm disruption is involved in the development of metabolic diseases and subfertility. An association between shift work and the incidence of PCOS in females was recently reported. This is a retrospective case-referent study in which peripheral blood samples were obtained from 101 control and 101 PCOS subjects. PCOS diagnoses were based on Rotterdam Consensus criteria. This study comprised 101 women with PCOS and 101 control volunteers, as well as Swiss albino mice treated with dehydroepiandrosterone (DHEA) to induce PCOS development. Gene expression analyses of circadian and steroidogenesis genes in human PBMC and mice ovaries and blood were executed by quantitative real-time PCR. We observed aberrant expression of peripheral circadian clock genes in PCOS, with a significant reduction in the core clock genes, circadian locomotor output cycles kaput (CLOCK) (P ≤ 0.00001), brain and muscle ARNT-like 1 (BMAL1) (P ≤ 0.00001) and NPAS2 (P ≤ 0.001), and upregulation of their negative feedback loop genes, CRY1 (P ≤ 0.00003), CRY2 (P ≤ 0.00006), PER1 (P ≤ 0.003), PER2 (P ≤ 0.002), DEC1 (P ≤ 0.0001) and DEC2 (P ≤ 0.00005). Transcript levels of an additional feedback loop regulating BMAL1 showed varied expression, with reduced RORA (P ≤ 0.008) and increased NR1D1 (P ≤ 0.02) in PCOS patients in comparison with the control group. We also demonstrated the expression pattern of clock genes in PBMCs of PCOS women at three different time points. PCOS patients also exhibited increased mRNA levels of steroidogenic enzymes like StAR (P ≤ 0.0005), CYP17A1 (P ≤ 0.005), SRD5A1 (P ≤ 0.00006) and SRD5A2 (P ≤ 0.009). Knockdown of CLOCK/BMAL1 in PBMCs resulted in a significant reduction in estradiol production, by reducing CYP19A1 and a significant increase in dihydrotestosterone production, by upregulating SRD5A1 and SRD5A2 in PBMCs. Our data also showed that CYP17A1 as a direct CLOCK-BMAL1 target in PBMCs. Phenotypic classification of PCOS subgroups showed a higher variation in expression of clock genes and steroidogenesis genes with phenotype A of PCOS. In alignment with the above results, altered expression of ovarian core clock genes (Clock, Bmal1 and Per2) was found in DHEA-treated PCOS mice. The expression of peripheral blood core clock genes in DHEA-induced PCOS mice was less robust and showed a loss of periodicity in comparison with that of control mice. N/A. We could not evaluate the circadian oscillation of clock genes and clock-controlled genes over a 24-h period in the peripheral blood of control versus PCOS subjects. Additionally, circadian genes in the ovaries of PCOS women could not be evaluated due to limitations in sample availability, hence we employed the androgen excess mouse model of PCOS for ovarian circadian assessment. Clock genes were assessed in the whole ovary of the androgen excess mouse model of PCOS rather than in granulosa cells, which is another limitation of the present work. Our observations suggest that the biological clock is one of the contributing factors in androgen excess in PCOS, owing to its potential role in modulating peripheral androgen metabolism. Considering the increasing prevalence of PCOS and the rising frequency of delayed circadian rhythms and insufficient sleep among women, our study emphasizes the potential in modulating circadian rhythm as an important strategy in PCOS management, and further research on this aspect is highly warranted. This work was supported by the RGCB-DBT Core Funds and a grant (#BT/PR29996/MED/97/472/2020) from the Department of Biotechnology (DBT), India, to M.L. B.S.J. was supported by a DST/INSPIRE Fellowship/2015/IF150361 and M.B.K. was supported by the Research Fellowship from Council of Scientific & Industrial Research (CSIR) (10.2(5)/2007(ii).E.U.II). The authors declare no competing interests. N/A.

Plasma Complement C1q/tumor necrosis factor-related protein 15 concentration is associated with polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common poignant endocrine disorder affecting women, posing a close association with metabolic syndrome and obesity. Existing literature characterizes PCOS with deranged levels of several adipokines and myokines. CTRP15 is a paralogue of adiponectin, mainly expressed by skeletal muscles, and plays a key role in insulin, glucose, and lipid metabolism. In the current study, we aim to determine the circulating levels of CTRP15 and evaluate its association with cardiometabolic and inflammatory parameters in PCOS women. This case-control study included 120 PCOS patients (60 Recurrent pregnancy loss (RPL) and 60 infertile (inf) PCOS) and 60 healthy non-PCOS controls. Serum levels of hs-CRP were measured by commercial kits, while serum levels of adiponectin and CTRP15 were determined using the ELISA technique. Serum levels of CTRP15 were significantly elevated in PCOS-RPL and PCOS-inf subgroups when compared to controls (94.80 ± 27.08 and 87.77 ± 25.48 vs. 54.78 ± 15.45, both P < 0.001). Moreover, serum adiponectin was considerably lower in the PCOS group and subgroups (P < 0.001), while serum hs-CRP, fasting insulin, HOMA-IR, and free testosterone were significantly higher when compared to the non-PCOS group (P < 0.05). Furthermore, CTRP15 closely associated with FSH, HOMA-IR, hs-CRP, and BMI. These results highlight a possible involvement of CTRP15 in the pathogenesis of PCOS. The elevated levels of CTRP15 might be a compensatory mechanism for the metabolic dysregulations (excess adiposity, insulin resistance, metaflammation) associated with the syndrome. Nevertheless, future studies are necessary to unravel the underlying mechanism.

The Prevalence of Insulin Resistance and Its Association With Thyroid-Stimulating Hormone and Obesity in Infertile Women With Different Polycystic Ovary Syndrome Phenotypes

The aim of this study was to investigate the prevalence of insulin resistance (IR) according to the phenotypic subgroups of polycystic ovary syndrome (PCOS) and to determine the associations of TSH levels and body mass index (BMI) with IR in infertile women with PCOS. In this cross-sectional study, we included 400 infertile women with a diagnosis of PCOS according to Rotterdam criteria who were referred to the infertility clinic of amir-al-Momenin University Hospital from April 2018- to January 2020. They were classified into four different phenotypic subgroups according to ESHRE guidelines. The homeostasis model (HOMA-IR) was used to measure IR. The prevalence of insulin resistance was 39.3% in infertile women with PCOS. Among women with PCOS, the commonest phenotype was type I (68%), with type II (18.2%), type III (8.8%), and type IV (5%), respectively. Furthermore, there was no significant difference in the prevalence of IR among different phenotypes of PCOS. Logistic regression analysis showed that the chance of insulin resistance was higher in overweight (OR: 1.76, 95% CI: 1.07, 2.88, P=0.024) and obese PCOS women (OR: 3.25, 95% CI: 1.86, 5.67, P&lt;0.001) compared with those who were normal or underweight. Moreover, the chance of IR was higher in PCOS women with TSH ≥2.5 μIU/ml as compared with those who had TSH &lt;2.5 μIU/ml (OR: 2.00, 95% CI: 1.18, 3.40, P&lt;0.001). Insulin resistance is a prevalent disorder among infertile Iranian women with PCOS BMI, and serum levels of TSH ≥2.5 μIU/ml are independent predictors of IR.

Oxidative stress promotes hyperandrogenism by reducing sex hormone-binding globulin in polycystic ovary syndrome

To determine the relationships between circulating sex hormone-binding globulin (SHBG) and oxidized low-density lipoprotein (ox-LDL), total oxidant status, total antioxidant capacity, oxidative stress index, malondialdehyde, and the high-density lipoprotein (HDL) inflammatory index in patients with polycystic ovary syndrome (PCOS) and to investigate the effect of oxidative stress on the expression of SHBG and its mechanism in HepG2 cells. Cross-sectional study. University hospital. A total of 533 women with PCOS and 292 control women were included. None. Circulating SHBG, hormones, and metabolic and oxidative stress indices were determined in all subjects. The effects of ox-LDL and ox-HDL on the mRNA and protein expression of SHBG and related transcription factors were observed in HepG2 cells. The HDL inflammatory index, total oxidant status, oxidative stress index, and malondialdehyde levels were significantly higher in the three PCOS subgroups with different SHBG levels than in the controls. The ox-LDL and total antioxidant capacity were higher in the PCOS subgroups with SHBG levels <75th percentile compared with the controls or the PCOS subgroup with SHBG levels ≥75th percentile. In HepG2 cells, the SHBG concentration in the culture supernatant, the mRNA levels of SHBG and hepatocyte nuclear factor-4α (HNF-4α), and the protein levels of HNF-4α were significantly lower in ox-LDL- and ox-HDL-treated cells than in the control cells and lipoprotein-treated cells. Oxidative stress inhibits the expression and secretion of SHBG by downregulating HNF-4α invitro and may be an important factor promoting the occurrence of hyperandrogenemia in PCOS.

THE HAIRY TRUTH: AMH, BMI, AND HYPERANDROGENISTIC SYMPTOMS IN PCOS WOMEN

Women with polycystic ovarian syndrome (PCOS) often present with elevated serum AMH levels as well as a higher BMI as a result of metabolic dysfunction. While both AMH and BMI have been strongly linked to fertility outcomes in PCOS patients, previous studies correlating the two have been controversial. Better understanding the link between AMH and BMI may provide important insight to the widely misunderstood metabolic and endocrine etiology of PCOS’ impacts on fertility. Hyperandrogenism and altered steroidogenesis is one of the defining features of PCOS that may play a key role in the relationship between BMI and AMH levels. Thus, we sought to better understand the relationship between hyperandrogenistic characteristics, BMI, and AMH levels in PCOS patients, compared to classical PCOS presentations. The purpose of this study was to determine the relationship between hyperandrogenism, AMH, and BMI levels in PCOS patients. Retrospective chart review at a private multi-site infertility center. Patients who underwent in-vitro fertilization (IVF) cycles between April 2017 and October 2020 with a diagnosis of PCOS, defined by the Rotterdam Criteria, were included. Patients were divided into two groups: those with hyperandrogenism and those without. Hyperandrogenic PCOS and classical PCOS subgroups were defined based on the presence or absence of self-reported adult acne and hair growth. Baseline characteristics were evaluated, and linear regression analysis was performed on PCOS patients to detect correlations between BMI, AMH, and clinical hyperandrogenism. Two sample t-tests and chi square analysis were used to analyze the data using SPSS (SPSS Inc., Chicago, IL, USA). A total of 330 patients were analyzed. We did not find a statistically significant correlation between BMI and AMH. While there was no statistically significant difference in BMI between the classical and hyperandrogenic PCOS groups, of note, there was a significantly higher AMH in the hyperandrogenic group, with a mean of 5.89, compared to 4.56 in the classical PCOS group (p = 0.008). However, when separated based on whether patients exhibited clinical hyperandrogenism, patients with no increased testosterone levels did exhibit a statistically significant negative correlation between BMI and AMH (p = .001). Comparatively, while there was a negative correlation between AMH and BMI in the clinical hyperandrogenism group, it was not statistically significant (p = .605). Our results demonstrate that there is an overall negative correlation between BMI and AMH amongst both classical and hyperandrogenic PCOS populations. Although this is only statistically significant in the classical PCOS group, these preliminary results may demonstrate a peek into the etiology of hyperandrogenic PCOS, as well as the relationship between BMI and AMH in this subgroup. Further research is needed to clarify the correlation between BMI and AMH and how testosterone, or lack thereof, may influence these levels.

The association between 24-hour ambulatory blood pressure measurement and selected biochemical and anthropometric parameters in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorders, which may contribute to the development of cardiovascular diseases. The aim of our study was to evaluate the association between of 24-hour ambulatory blood pressure measurement (ABPM) and selected biochemical and anthropometric parameters in women with PCOS. The study involved 153 Polish, Caucasian women with PCOS hospitalized in the Department of Endocrinology Gynecology from January 2018 to March 2020. All women had stable body mass during the 3-month period. ABPM was performed using a portable lightweight device with oscillometric technology accepted by International Protocol of European Society of Hypertension (ABPM, HolCARD CR-07, Poland). The first factor taken into consideration was the variability phenotypic subgroups of PCOS on the values of 24-hour ABPM. We revealed that the daytime and night-time systolic and diastolic blood pressure values were significantly higher in phenotype A subgroup than in other subgroups. Moreover, daytime and night-time systolic and diastolic blood pressure value as well as day-time heart ratio value were significantly higher in subgroup with than without hyperandrogenemia. The obese women with PCOS were characterized of the highest value of all night-time measurements among women with PCOS and normal weight, overweight or obesity. In addition, insulin resistance in the PCOS subgroup was associated with lower value of systolic, diastolic blood pressure and both at daytime and night-time heart rate value than in insulin sensitive PCOS subgroup. Hyperandrogenemia and obesity were the crucial influencing factors on 24-hour ABPM in the group of women with PCOS. In addition, hypertension, apart from visceral obesity, hyperinsulinemia and insulin resistance, could be considered as component of metabolic syndrome in women with PCOS.

Skeletal Muscle Health in Polycystic Ovary Syndrome: Protective Effect of Hyperandrogenism or Detrimental Effect of Insulin Resistance? A Systematic Review and Meta-Analysis

Women with polycystic ovary syndrome (PCOS) exhibit reduced skeletal muscle insulin-mediated glucose uptake. Altered muscle mass may affect insulin resistance (IR) and inflammation, thereby potentially aggravating reproductive status including ovulatory cyclicity and fertility potential. However, the relationship between PCOS and skeletal muscle mass is elusive given conflicting reports on protective or detrimental influence of PCOS endocrine derangements (hyperandrogenism, IR) on muscle. We evaluated whether muscle mass and function are affected by PCOS in response to a call to elucidate musculoskeletal alterations in the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Web of Science, and Scopus were searched (January 1990 to September 2020) to identify observational studies on skeletal muscle mass (lean tissue mass) and function (strength) in PCOS and control groups. The primary outcome was total lean body mass (LBM) or fat-free mass (FFM). Data were pooled by random-effects models and expressed as weighted mean differences and 95% confidence intervals. Forty-five studies (n = 3,676 [1,854, PCOS; 1,822, controls]) were eligible. Forty-one evaluated lean tissue mass and five strength. PCOS groups had increased total (0.83 [0.08, 1.58] kg; P=0.03; I2 = 72.0%) yet comparable trunk (0.84 [-0.37, 2.05] kg; P = 0.15; I2 = 73.0%) LBM/FFM. There were no associations between mean differences of groups in total testosterone (TT) or homeostatic model assessment of IR (HOMA-IR) and total/trunk LBM/FFM (All: P ≥ 0.75) by meta-regressions. However, mean differences of groups in body mass index (BMI) were associated with total (0.65 [0.23, 1.06] kg; P < 0.01; I2 = 56.9%) and trunk (0.56 [0.11, 1.01] kg; P = 0.02; I2 = 42.8%) LBM/FFM. Accordingly, PCOS sub-group with overweight/obesity (BMI ≥ 25 kg/m2) exhibited greater total LBM/FFM than controls (1.58 [0.82, 2.34] kg; P < 0.01; I2 = 64.0%) unlike a lean (BMI < 25 kg/m2) sub-group (-0.45 [-1.94, 1.05] kg; P = 0.53; I2 = 69.5%). Some study results were contradictory (i.e., increased appendicular mass or strength in PCOS group or comparable findings between groups) and study methodology varied; thus, inclusion in meta-analyses was not possible. PCOS cohorts have a tendency for increased total and trunk lean tissue mass likely attributed to obesity. However, most critically, whether PCOS influences other lean tissue areas (appendicular), morphology, and function is unclear. Our observations do not support any protective/detrimental influence of hyperandrogenism (TT) or IR (HOMA-IR) on lean mass. Heterogeneity among studies warrants research to address any contributions of lifestyle, healthcare, and biological factors to observed differences for future guideline recommendations to improve PCOS musculoskeletal and reproductive health (www.crd.york.ac.uk/PROSPERO ID, CRD42020203490).

Obesity, but not hyperandrogenism or insulin resistance, predicts skeletal muscle mass in reproductive-aged women with polycystic ovary syndrome: A systematic review and meta-analysis of 45 observational studies.

Women with polycystic ovary syndrome (PCOS) exhibit reduced muscle insulin-mediated glucose uptake, potentially attributed to altered muscle mass; however, this is inconclusive. Altered muscle mass may aggravate PCOS complications. Our systematic review and meta-analysis evaluated whether PCOS alters muscle mass and function. Databases (MEDLINE, Web of Science, Scopus) were searched through September 2, 2020, for studies documenting skeletal muscle mass (lean tissue mass) and function (strength) in PCOS and control groups. The primary outcome was total lean body mass (LBM) or fat-free mass (FFM). Data were pooled by random-effects models and expressed as mean differences and 95% confidence intervals. Forty-five studies (n= 3676 participants) were eligible. Women with PCOS had increased total (0.83 [0.08,1.58]kg; p= 0.03; I2 = 72.0%) yet comparable trunk (0.84 [-0.37,2.05]kg; p= 0.15; I2 = 73.0%) LBM or FFM versus controls. Results of meta-regression analyses showed no associations between mean differences between groups in total testosterone or homeostatic model assessment of insulin resistance and total or trunk LBM or FFM (All: p≥ 0.75). Mean differences in body mass index (BMI) were associated with total (0.65 [0.23,1.06]kg; p< 0.01; I2 = 56.9%) and trunk (0.56 [0.11,1.01]kg; p= 0.02; I2 = 42.8%) LBM or FFM. The PCOS subgroup with BMI ≥ 25 kg/m2 had greater total LBM or FFM versus controls (1.58 [0.82,2.34]kg; p< 0.01; I2 = 64.0%) unlike the PCOS subgroup with BMI < 25 kg/m2 (-0.45 [-1.94,1.05]kg; p= 0.53; I2 = 69.5%). Appendicular lean mass and muscle strength data were contradictory and described narratively, as meta-analyses were impossible. Women with PCOS have higher total and trunk lean tissue mass attributed to overweight/obesity, unlike hyperandrogenism or insulin resistance.

The Relationship of Anti-Mullerian Hormone in Polycystic Ovary Syndrome Patients with Different Subgroups.

PurposeTo explore the value of anti-Mullerian hormone (AMH) in patients with polycystic ovary syndrome (PCOS) with different phenotypes and ages, and to identify the relationship between hyperandrogenism (HA) and polycystic ovary morphology (PCOM), in a Chinese cohort.MethodsA total of 2262 women (1631 with PCOS and 631 controls) were enrolled. The serum AMH and total testosterone (TT) were analyzed, the AMH levels of each subgroup were compared, and the value of each phenotype and age group of patients with PCOS was evaluated.ResultsThe level of AMH in women with PCOS (mean±SD, 8.63±4.73 ng/mL) was higher than that in controls (5.57±3.31 ng/mL) (P<0.01). The level of AMH in the PCOM subgroup (11.19±6.4 ng/mL) was significantly higher than that in the HA subgroup (8.58±4.74 ng/mL) (P<0.01), and both were higher than that in controls (P<0.01). AMH was higher in PCOS patients than in controls, but the same values were found in subgroups of PCOS patients under 30 years old.ConclusionAMH changed in different subgroups of PCOS, which was the possible reason why AMH was not a diagnostic indicator. However, AMH could help to differentiate between clinical subgroups, as it was strongly related with PCOM but not with HA. AMH changed substantially with age, but was stable in PCOS patients under 30 years old.

Serum pregnancy-associated placental protein-a (PAPP-A) levels are increased in polycystic ovary syndrome (PCOS) in women with oligo-anovulation

Background/Aim: Pregnancy associated placental protein-A (PAPP-A) is a zinc-binding metalloproteinase with a key role in insulin like growth factor (IGF) pathway, and potential atherogenic effects. There is little information in the literature regarding PAPP-A levels in Polycystic ovary syndrome (PCOS). We aimed to investigate the serum PAPP-A levels among non-obese women with PCOS as a cardiovascular risk marker. Methods: Non-obese women of reproductive age (18-35 years of age) diagnosed with PCOS according to Rotterdam Consensus Conference criteria were included in this case-control study. Serum PAPP-A levels were compared with independent samples t-test between two main groups (PCOS and control) and investigated in PCOS subgroups as PCOS patients were further classified according to main phenotypes (hyperandrogenism and oligo-anovulation). Results: A total of 41 women with PCOS and 40 age- and body mass index- matched controls were included in the analysis. The serum PAPP-A levels of the control and PCOS groups, and of PCOS patients with hyperandrogenism were similar (P=0.128, P=0.261, respectively). However, the serum PAPP-A levels of those with oligo-anovulation was higher than those without (P=0.006), and that of women without oligo-anovulation was comparable to that of the control group (P=0.613). Conclusion: Lean and young PCOS women with oligo-anovulation had increased serum levels of PAPP-A when compared to women without. Prospective studies are needed to uncover the long-term cardiovascular risk of elevated PAPP-A levels in PCOS women with oligo-anovulation.