Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women. Clinical manifestations include hyperandrogenism, chronic anovulation, polycystic ovaries and being ...frequently accompanied by insulin resistance (IR) and obesity. MicroRNAs (miRNAs) are short non-coding RNAs which are involved in the regulation of gene expression at the post-transcriptional level. Altered miRNAs levels have been showed to be associated with a variety of diseases including diabetes, endometriosis and cancer. In recent years, more and more evidence suggests abnormal expression of miRNAs are detected in granulosa cells, theca cells, adipose tissue, follicular fluid, serum and peripheral blood leukocytes of women with PCOS and display vital role in the occurrence and development of PCOS. This will shed light on new strategies for the diagnosis and treatment of this syndrome. In this paper, we will review the recent research on miRNAs with respect to PCOS.
•MiRNAs are involved in broad physiological processes.•Dysregulated miRNAs could be detected within cells and extracelluar fluids of Polycystic Ovary Syndrome patients and were involved in the pathogenesis of Polycystic Ovary Syndrome.
Polycystic ovary syndrome (PCOS) impacts approximately 6%-10% of women worldwide, with hallmark features of hyperandrogenism, irregular menses, infertility, and polycystic appearing ovaries on ...ultrasound. In addition, PCOS is associated with several endocrine and metabolic disorders, including obesity, insulin resistance and diabetes mellitus, hypertension, dyslipidemia and metabolic syndrome, which all increase the risk for subclinical cardiovascular disease (CVD), the presence of altered vascular endothelium without overt CVD. In this review, we summarize the most recent literature regarding subclinical CVD in women with PCOS, including markers such as flow-mediated dilation, arterial stiffness, coronary artery calcium scores, carotid intima-media thickness and visceral and epicardial fat.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ...ultrasonography, and affects 5-10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed. Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5-15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, one particular surgical method, called laparoscopic ovarian drilling (LOD), has been proposed as an alternative treatment. LOD results in an overall spontaneous ovulation rate of 30-90% and final pregnancy rates of 13-88%. These benefits are more significant for women with CC-resistant PCOS. Although the intra- and post-operative complications and sequelae are always important, we believe that a better understanding of the pathophysiological changes and/or molecular mechanisms after LOD may provide a rationale for this procedure. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of "toxic" follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the "hypothalamus-pituitary-ovary" axis and subsequent spontaneous ovulation. The detailed local and systematic changes in PCOS women after LOD are comprehensively reviewed in the current article.
Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 ...infection.
Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN).
The main outcome was the incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS.
We identified 21 292 women with a coded diagnosis of PCO/PCOS and randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 (95% CI: 1.27-1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14-1.63), P = 0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 (1.05-1.56), P = 0.015).
Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic.
Women with polycystic ovary syndrome (PCOS) have an increased risk of cardio-metabolic disease, which have been identified as a risk factor for COVID-19. To investigate whether the increased metabolic risk in PCOS translates into an increased risk of COVID-19 infection, we carried out a population-based closed cohort study in the UK during its first wave of the SARS-CoV-2 pandemic (January to July 2020), including 21 292 women with PCOS and 78 310 controls matched for sex, age and general practice location. Results revealed a 52% increased risk of COVID-19 infection in women with PCOS, which remained increased at 28% above controls after adjustment for age, BMI, impaired glucose regulation and other explanatory variables.
Summary
Context
Adipsin, a protein secreted mainly from the adipose tissue, is a structural homologous of complement factor D, a rate‐limiting enzyme of the alternative complement system. Growing ...evidence suggests that the alternative complement system plays a role both in the regulation of energy homoeostasis and in the atherosclerosis. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease.
Objective
To ascertain whether circulating adipsin levels are altered in women with PCOS, and whether there is an association between adipsin and metabolic parameters or carotid intima media thickness (CIMT).
Participants
A total of 144 women with PCOS and 144 age‐ and BMI‐matched controls without PCOS were recruited for this cross‐sectional study.
Main Outcome Measures
Circulating adipsin levels were measured using ELISA. Metabolic, hormonal parameters and CIMT were also determined.
Results
Adipsin levels were significantly elevated in women with PCOS compared with controls (91·52 ± 14·11 vs 60·31 ± 9·71 ng/ml, P < 0·001). Adipsin positively correlated with BMI, homoeostasis model assessment of insulin resistance (HOMA‐IR), free testosterone, high‐sensitivity C‐reactive protein (hs‐CRP) and CIMT in both groups. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 3·25 for patients in the highest quartile of adipsin compared with those in the lowest quartile (OR=3·25, 95% CI=2·64–4·00, P = 0·016). Our findings further indicate that BMI, HOMA‐IR, hs‐CRP and free testosterone are independent factors influencing serum adipsin levels and that adipsin is an independent predictor for CIMT.
Conclusion
Circulating adipsin levels are significantly higher in women with PCOS, and the peptide is closely related to increased cardiovascular risk and metabolic disturbances.
To investigate the expression and clinical significance of programmed cell death 4 (PDCD4), a novel metabolism-associated gene, during polycystic ovary syndrome (PCOS) pathogenesis.
Case-control ...study.
University hospital.
A total of 77 PCOS patients and 67 healthy women as matched controls.
PDCD4 expression in peripheral blood mononuclear cells analyzed by quantitative real-time polymerase chain reaction, and apoptosis of granulosa cells (GCs) detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and small-interfering RNA.
PDCD4 expression, body mass index (BMI), insulin 0, insulin 120, glucose 120, homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for β-cell function (HOMA-β), triglycerides, high-density lipoprotein (HDL), and GC apoptosis.
The PCOS patients had higher PDCD4 expression, but BMI was similar as matched with the obese group, which positively correlated with BMI, insulin 0, insulin 120, glucose 120, HOMA-IR, HOMA-β, triglycerides and negatively correlated with HDL (P<.05). After metformin treatment, PDCD4 expression was distinctly down-regulated for the obese women with PCOS with insulin resistance. Compared with the healthy controls, the apoptosis percentage of GCs was higher in the PCOS group and was decreased by knocking down PDCD4. Furthermore, expression of proapotosis factor Bax and the Bax/Bcl-2 ratio were lower, whereas the expression of antiapoptosis factor Bcl-2 was increased. In a multivariate logistic regression analysis, the level of PDCD4 expression independently related to the odds of PCOS risk after controlling for estradiol and insulin 120 (odds ratio 1.318).
Our study suggests for the first time that higher PDCD4 expression might play an important role in PCOS pathogenesis by affecting obesity, insulin resistance, lipid metabolism disorders, and GC apoptosis.
This study aims to assess the therapeutic effects of a well-known component (puerarin) obtained from a Chinese herb root in patients with polycystic ovary syndrome (PCOS).
Women with premature ...ovarian failure (POF) were assigned to the obese group (body mass index BMI ≥24 kg/m2 and waist hip ratio WHR >0.85) or non-obese group (group 3, n = 21). Obese patients were further randomly assigned to the obese treatment group (group 1, n = 15) and obese control group (group 1, n = 15). All patients received standard treatment (Diane-35, 1 tablet/d, orally, plus metformin, 1.5 g/d, orally). In addition to the standard modality, patients in group 1 and group 3 also orally received 150 mg/d of puerarin tablets for 3 months. Venous blood was drawn before and after treatment. Then, the metabolic and antioxidant biomarkers were measured. The normality of distribution of the data was tested using the Kolmogorov-Smirnov method. The baseline characteristics were analyzed using one-factor analysis of variance (ANOVA), and post-hoc was performed using the least significance difference (LSD)-t test.
Significantly improved blood levels of sex hormone binding globulin (SHBG) and superoxide dismutase (SOD) were observed in patients who received the additional treatment of puerarin, regardless of their lean or obese status, while these were not observed in patients who did not receive puerarin. Furthermore, obese patients with PCOS had significantly lower systolic blood pressure, total cholesterol, and testosterone blood levels, when compared with before treatment.
The addition of puerarin to the present treatment protocol can be considered for the management of metabolic disorders and hyperandrogenism in PCOS patients.
Gonadotropin-releasing hormone (GnRH) analogues are commonly used in clinical practice to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization/ Intra-Cytoplasmic Sperm ...Injection (IVF/ICSI) cycles. This review aimed to summarize the available evidence comparing the effects of conventional GnRH antagonist protocols, the most commonly used GnRH antagonist protocols, and GnRH agonist protocols on IVF/ICSI outcomes in women with polycystic ovary syndrome (PCOS). A comprehensive electronic search was carried out in Pubmed, Cochrane CENTRAL, Scopus, Web of Science, CINAHL, TRIP, ClinicalTrials.gov and ISRCTN registry from inception until 24 November 2020 without any language or date restrictions. In addition, reference lists of eligible studies and previous meta-analyses were hand-searched to identify relevant studies. Eligible randomized controlled trials were those designed to compare the effects of conventional GnRH antagonist protocols and GnRH agonist protocols on IVF/ICSI outcomes in PCOS subjects. The Cochrane ROB 2.0 tool was used to assess the risk of bias of each study, and the GRADE assessment was used to evaluate the overall quality of evidence. Data synthesis and analyses were done using Review Manager 5.3 with the assistance of Revman Web. A random-effects model was used for all meta-analysis. Dichotomous outcomes were reported as Relative Risk (RR) and continuous outcomes as Weighted Mean Difference (WMD), both with 95% CIs. The primary outcomes were Live birth rate, Ongoing pregnancy rate, and Ovarian hyperstimulation syndrome (OHSS) rate. Other IVF outcomes were considered secondary outcomes. We included ten studies with 1214 randomized PCOS women. Using GnRH antagonist protocols led to a significantly lower OHSS rate (RR = 0.58; 95% CI: 0.44 to 0.77, P = 0.0002), shorter stimulation duration (WMD = - 0.91; 95% CI: -1.45 to - 0.37 day, P = 0.0009), lower gonadotropin consumption (WMD = - 221.36; 95% CI: - 332.28 to - 110.45 IU, P < 0.0001), lower E2 levels on hCG day (WMD = - 259.21; 95% CI: - 485.81 to - 32.60 pg/ml, P = 0.02), thinner endometrial thickness on hCG day (WMD = - 0.73; 95% CI: - 1.17 to - 0.29 mm, P = 0.001), and lower number of retrieved oocytes (WMD = - 1.82; 95% CI: - 3.48 to - 0.15 oocytes, P = 0.03). However, no significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and cycle cancellation rate were seen between the GnRH antagonist protocols and the long GnRH agonist one. Although more cycles were cancelled due to poor ovarian response in the GnRH antagonist protocol (RR = 4.63; 95% CI: 1.49 to 14.41, P = 0.008), similar rates of cancellation due to risk of OHSS were noticed in both groups. The differences in IVF/ICSI outcomes may arise from the different patterns of gonadotropins suppression that the GnRH analogues exhibit during the early follicular phase of IVF/ICSI cycles and the divergent direct impacts of these analogues on ovaries and endometrial receptivity. The main evidence limitation was Imprecision. Conventional GnRH antagonist protocols represent a safer and more cost-effective treatment choice for PCOS women undergoing IVF/ICSI cycles than the standard long GnRH agonist protocol without compromising the IVF/ICSI clinical outcomes. The study had no sources of financial support and was prospectively registered at PROSPERO (International Prospective Register of Systematic Reviews) under registration number (CRD42021242476).
•PCOS is developmentally programmed by in utero androgen (dihydrotestosterone) exposure.•PCOS caused dysregulation of genes related to ovarian function and mitochondria in the ovary.•Ovarian ...mitochondrial ultrastructure was affected in PCOS mice.•PCOS ovaries consumed more oxygen than the controls.•Ovaries of PCOS mice were structurally and functionally compromised at birth.
Polycystic ovary syndrome (PCOS) is a common form of anovulatory infertility with a strong hereditary component but no candidate genes have been found. The inheritance pattern may be due to in utero androgen programming on gene expression and mitochondria. Mitochondria are maternally inherited and alterations to mitochondria after fetal androgen exposure may explain one of the mechanisms of fetal programming in PCOS. Our aim was to investigate the role of excessive prenatal androgens in ovarian development by identifying how hyperandrogenemia affects gene expression and mitochondria in neonatal ovary. Pregnant dams were injected with dihydrotestosterone on days 16–18 of pregnancy. Day 0 ovaries were collected for gene expression and mitochondrial studies. RNAseq showed differential gene expressions which were related to mitochondrial dysfunction, fetal gonadal development, oocyte maturation, metabolism, angiogenesis, and PCOS. Top 20 up and downregulated genes were validated with qPCR and Western Blot. Transcriptional pathways involved in folliculogenesis and genes involved in ovarian and mitochondrial function were dysregulated. Further, DHT exposure altered mitochondrial ultrastructure and function by increasing mitochondrial oxygen consumption and decreasing mitochondrial efficiency with increased proton leak within the first day of life. Our data indicates that one path that leads to PCOS begins at birth and is programmed in utero by androgens.
Abstract
Context:
Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters.
Objectives:
To investigate the ...prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed.
Design:
Population-based follow-up.
Setting:
Northern Finland Birth Cohort 1966 with 15-year follow-up.
Participants:
At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS.
Interventions:
Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed.
Main Outcomes:
Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46.
Results:
Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety.
Conclusions:
Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression.
We studied psychological distress in women with PCOS symptoms and found high anxiety and depression rates in women with PCOS or isolated hirsutism lasting until perimenopausal age.
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