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1.
The Role of Genetics, Epigenetics and Lifestyle in Polycystic Ovary Syndrome Development: the State of the Art.
Bruni, V, Capozzi, A, Lello, S
Reproductive sciences (Thousand Oaks, Calif.). 2022;(3):668-679
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease affecting about 20-25% of women in reproductive age. Different mechanisms could contribute to the development of its typical clinical features (i.e. hirsutism, acne, oligo-amenorrhea, alopecia). Some genetic and epigenetic aspects and lifestyle changes seem to be involved in PCOS development. In this review, we shall summarize data from principal studies evaluating the impact of major genetic, epigenetic and environmental factors on the appearance of this female disorder. Literature review and analysis of the most relevant data until May 2020. Current data suggest the importance of genetics and epigenetics in the appearance of PCOS. Several genes, including those related to adrenal and ovarian steroidogenesis as well as those associated with hormonal response to gonadotrophins, androgens and insulin, have been demonstrated to be associated with PCOS. Besides, the phenomenon of methylation of genes and the presence of specific microRNA (miRNA) could take part in PCOS aetiology. Intrauterine exposure to androgens, glucocorticoids and/or some stressful conditions for foetus could contribute to the development of PCOS and other disorders observed in adolescence and later (e.g. premature adrenarche, atypical puberty, metabolic syndrome). Emerging studies report a theoretical role of endocrine disruptors, intestinal dysbiosis and Advanced Glycation End products (AGEs) in PCOS. PCOS is a polygenic and multifactorial hormonal and metabolic dysfunction. An appropriate knowledge of personal and/or family history, lifestyle and nutritional habits of PCOS patients has a great importance to early identify and manage this syndrome.
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2.
Polycystic ovarian syndrome: signs and feedback effects of hyperandrogenism and insulin resistance.
Hernández-Jiménez, JL, Barrera, D, Espinoza-Simón, E, González, J, Ortíz-Hernández, R, Escobar, L, Echeverría, O, Torres-Ramírez, N
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2022;(1):2-9
Abstract
Polycystic ovary syndrome (PCOS) is a disease whose diagnosis is based on the detection of hyperandrogenism (HA) and ovulatory dysfunction. Women with PCOS frequently develop insulin resistance (IR), which generates a metabolic condition that involves a decrease in the action of insulin at the cellular level and is linked to compensatory hyperinsulinemia (HI). In PCOS, the ovary remains sensitive to the action of insulin. Additionally, it has been observed that the main effect of insulin in the ovary is the stimulation of androgen synthesis, resulting in HA, one of the fundamental characteristics of the PCOS. In this sense, the excess of androgens favors the development of IR, thus perpetuating the cycle of IR-HI-HA, and therefore PCOS. Moreover, mitochondrial dysfunction is present in PCOS patients and is a common feature in both IR and HA. This review places electron transfer as a key element in HA and IR development, with emphasis on the relationship between androgen biosynthesis and mitochondrial function. Indeed, metformin has been involved in repair mitochondrial dysfunction, decrease of oxidative stress, reduction of androgens levels and the enhancing of insulin sensitivity. Therefore, we propose that treatment with metformin could decrease HI and consequently HA, restoring, at least in part, the metabolic and hormonal disorders of PCOS.
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3.
Effects of Tea Consumption on Anthropometric Parameters, Metabolic Indexes and Hormone Levels of Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Shen, W, Pan, Y, Jin, B, Zhang, Z, You, T, Qu, Y, Han, M, Yuan, X, Zhang, Y
Frontiers in endocrinology. 2021;:736867
Abstract
OBJECTIVE Our aim was to conduct a systematic review and meta-analysis to assess the effectiveness and safety of tea supplements for patients with polycystic ovary syndrome (PCOS). METHODS We conducted searches of the published literature in PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), VIP database, and Wanfang Database in 1985 to September 2021. Data from randomized controlled trials (RCTs) were obtained to assess the effects of tea versus placebo in women with PCOS. Weighted mean differences (WMDs) were pooled using a random-effects model or risks ratios (RRs) using a random-effects model. RESULTS Six RCTs (235 participants) were included in our systematic review. Tea supplements as adjuvant therapy led to greater improvement in body weight (WMD -2.71, 95% CI -4.95 to -0.46, P = 0.02, I2 = 0%), fasting blood glucose (FBG: WMD -0.40, 95% CI -0.59 to -0.20, P < 0.0001, I2 = 0%) and fasting insulin (FINS: WMD -3.40, 95% CI -4.76 to -2.03, P < 0.00001, I2 = 0%) when compared with placebo. There were no significant differences of body mass index, waist circumference, hip circumference, waist-to-hip ratio (WHR), body fat rate, total testosterone, free testosterone (FT), dehydroepiandrosterone, luteinizing hormone or follicular-stimulating hormone (FSH) between the two groups. In addition, subgroup analysis suggested that green tea was effective on body weight, FINS, FBG, FT, and FSH, and herbal tea can also reduce FT levels, tea supplements had a significant impact on FBG and FSH in trials with intervention duration ≥ 3 months, and intervention lasting less than 3 months can improve FINS. Tea had significant effect on reducing WHR, FBG and FSH in Asian PCOS patients, but not in Caucasians. And there was no statistically significant effect of tea on weight and FINS in Asians, but it was effective for Caucasian participants. Compared with placebo, tea supplements did not cause significant adverse reactions (RR 1.45, 95% CI 0.30 to 6.90, P = 0.65, I2 = 0%). CONCLUSION This meta-analysis suggests that consumption of tea supplementation in women with PCOS could significantly decrease the levels of FBG and FINS as well as reduce body weight. Especially green tea, not only has the above effects, but also has a significant effect on improving a variety of reproductive hormone indexes. Furthermore, tea supplementation is a relatively safe therapy for PCOS patients. SYSTEMATIC REVIEW REGISTRATION PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=212755, identifier CRD42021249196.
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4.
Vitamin D and Polycystic Ovary Syndrome: a Narrative Review.
Mu, Y, Cheng, D, Yin, TL, Yang, J
Reproductive sciences (Thousand Oaks, Calif.). 2021;(8):2110-2117
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of reproductive age women and contributes to metabolic dysfunctions including insulin resistance (IR) and dyslipidemia. Vitamin D is a steroid hormone, which is involved in calcium metabolism and bone structure and has a potential role in the prevention of many illnesses, including cancers, autoimmune disorders, hypertension, diabetes, and obesity. Recently, it has been reported that vitamin D deficiency was a common complication of PCOS and vitamin D status was associated with reproductive ability, metabolic alterations, and mental health of PCOS patients. This review summarizes the advances between vitamin D status and the pathophysiological process of PCOS. Vitamin D level was negatively associated with serum androgen level. Vitamin D treatment could reduce serum androgen and anti-MüllerianHormone (AMH) levels, and decrease endometrial thickness, which resulted in improvement of menstrual cycle and folliculogenesis of PCOS patients. Moreover, vitamin D concentrations were negatively correlated with parameters of IR and body fat mass. Vitamin D supplementation has beneficial effects on IR and lipid metabolism. In addition, a positive of vitamin D on mental health of PCOS patients was proposed. Understanding the relationship between vitamin D status and the symptoms of PCOS patients is of great clinical significance to treat and prevent the progression of PCOS.
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5.
Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training.
Jerobin, J, Ramanjaneya, M, Bettahi, I, Parammal, R, Siveen, KS, Alkasem, M, Aye, M, Sathyapalan, T, Skarulis, M, Atkin, SL, et al
Lipids in health and disease. 2021;(1):34
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is associated with obesity, diabetes, and insulin resistance. The circulating C1Q/TNF-related proteins (CTRP-2, CTRP-9) and growth differentiation factors (GDF-8, GDF-15) contribute to glucose and lipid homeostasis. The effects of intralipids and insulin infusion on CTRP-2, CTRP-9, GDF-8 and GDF-15 in PCOS and control subjects before and after chronic exercise training were examined. METHODS Ten PCOS and nine healthy subjects were studied at baseline status and after moderate-intensity chronic exercise training (1 h exercise, 3 times per week, 8 weeks). All participants were infused with 1.5 mL/min of saline or intralipids (20%) for 5 h, and during the last 2 h of saline or intralipids infusion hyperinsulinemic-euglycemic clamp (HIEC) was performed. CTRP-2, CTRP-9, GDF-8 and GDF-15 levels were measured at 0, 3 and 5 h. RESULTS Intralipids dramatically increased CTRP-2 levels in PCOS (P = 0.02) and control (P = 0.004) subjects, which was not affected by insulin infusion or by exercise. Intralipids alone had no effects on CTRP-9, GDF-8, or GDF-15. Insulin increased the levels of GDF-15 in control subjects (P = 0.05) during the saline study and in PCOS subjects (P = 0.04) during the intralipid infusion. Insulin suppressed CTRP9 levels during the intralipid study in both PCOS (P = 0.04) and control (P = 0.01) subjects. Exercise significantly reduced fasting GDF-8 levels in PCOS (P = 0.03) and control (P = 0.04) subjects; however, intralipids infusion after chronic exercise training increased GDF-8 levels in both PCOS (P = 0.003) and control (P = 0.05) subjects and insulin infusion during intralipid infusion reduced the rise of GDF-8 levels. CONCLUSION This study showed that exogenous lipids modulate CTRP-2, which might have a physiological role in lipid metabolism. Since chronic exercise training reduced fasting GDF-8 levels; GDF-8 might have a role in humoral adaptation to exercise. GDF-15 and CTRP-9 levels are responsive to insulin, and thus they may play a role in insulin responses.
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6.
Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women.
Jamshidi, M, Mohammadi Pour, S, Bahadoram, M, Mahmoudian-Sani, MR, Saeedi Boroujeni, A
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2021;(1):33-44
Abstract
Polycystic ovary syndrome (PCOS) involves abnormalities in ovarian, reproductive, and metabolic systems. Genetic polymorphisms associated with individual differences and variations might be related to complex disorders with unknown causes, including PCOS. Several leading genetic markers with known cellular functions have been identified among Iranian women presenting with PCOS. In particular, the existing evidence shows a significant relationship between PCOS and the following genetic polymorphisms: rs2275913 (interleukin-17A), rs9927163 (interleukin-32), Pro12Ala (peroxisome proliferator-activated receptor-γ), rs17173608 (chemerin), rs2236242 (vaspin), ApaI (vitamin D receptor), and rs7895833 (sirtuin 1). In addition, a higher risk of PCOS is associated with the rs2910164 (microRNA 146a), rs2241766 (adiponectin), -34 T/C (cytochrome 17), and rs1800682 (Fas) polymorphisms. Furthermore, protective effects against PCOS have been reported for the A4223C polymorphism of adenosine deaminase 1. Overall, the available data indicate that Iranian women with PCOS have a higher prevalence of polymorphisms in inflammation- and metabolism-related genes, but not in insulin-related genes. More extensive studies are needed to identify the ethnicity-related genetic associations in PCOS.
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7.
Implementing the international evidence-based guideline of assessment and management of polycystic ovary syndrome (PCOS): how to achieve weight loss in overweight and obese women with PCOS?
Lie Fong, S, Douma, A, Verhaeghe, J
Journal of gynecology obstetrics and human reproduction. 2021;(6):101894
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Many of these women are overweight or obese. A minor weight loss of 5%-10% can significantly reduce reproductive, metabolic and psychological symptoms of PCOS and is recommended as a first step in the treatment of overweight or obese women with PCOS. Many weight loss programs have been proposed, but optimal methods on how to achieve the recommend weight loss are lacking. The aim of this systematic review was to generate practical tools for health professionals to guide women with PCOS towards a sustainable healthier lifestyle. PRISMA guidelines were used to conduct the systematic review. Eleven randomized controlled trials were found eligible for inclusion. Lifestyle modification strategies consisted of a diet, physical exercise, behavioural coaching or combined interventions. Mean weight loss ranged from +0.5 to -10.6 % of the initial body weight. However, the majority of the studies reported considerable drop-out rates varying between 12% and 47%. The heterogeneity of the described interventions and the high drop-out rates impede extrapolation of these results to daily clinical care. Hence, none of the described interventions seems superior to another in achieving substantial weight loss. In conclusion, the need for obtaining a healthier weight in overweight and obese women with PCOS is now well accepted. However, achieving this goal remains a challenge for both patients and healthcare providers. More research focusing on the multidisciplinary approach of lifestyle modification advice in daily practice is needed.
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8.
The effects of canola and olive oils consumption compared to sunflower oil, on lipid profile and hepatic steatosis in women with polycystic ovarian syndrome: a randomized controlled trial.
Yahay, M, Heidari, Z, Allameh, Z, Amani, R
Lipids in health and disease. 2021;(1):7
Abstract
BACKGROUND Polycystic Ovarian Syndrome (PCOS) is one of the most common endocrinopathies and metabolic disorders in women during their reproductive years. It is often associated with dyslipidemia and other risk factors of cardiovascular diseases (CVD). This study was aimed to evaluate dietary intervention effects with canola and olive oils compared to sunflower oil on lipid profile and fatty liver severity among women with PCOS. METHOD This study was a 10-week intervention including 72 women with PCOS. Patients were randomly assigned to three groups for receiving 25 g/day canola, olive, or sunflower oils for 10 weeks. The primary and secondary outcomes were to assess changes in lipid profile and in fatty liver severity, respectively. RESULT At the end of the study, 72 patients with a mean age of 29.31 were analysed. Canola oil consumption resulted in a significant reduction in serum levels of TG (P = 0.002) and TC/HDL (P = 0.021), LDL/HDL (P = 0.047), and TG/HDL (P = 0.001) ratios, however, there was no significant reduction in lipid profile following olive oil consumption. Canola (P < 0.001) and olive oils (P = 0.005) could significantly reduce the fatty liver grade. Moreover, HOMA-IR in both canola (P < 0.001) and olive (P = 0.004) groups was significantly decreased. CONCLUSION In total, compared to olive and sunflower oils, significant improvements in lipid profile, liver function, and HOMA-IR were observed following canola oil consumption in women with PCOS. TRIAL REGISTRATION IR.MUI. RESEARCH REC.1397.315. Registered 30 JUNE 2019 - Retrospectively registered, https://www.irct.ir/trial/38684.
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9.
Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials.
Wang, L, Wen, X, Lv, S, Tian, S, Jiang, Y, Yang, X
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(5):446-455
Abstract
OBJECTIVE The purpose of this meta-analysis was to evaluate the effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome (PCOS). METHODS We performed a literature search of databases and identified randomized controlled trials (RCTs) published prior to December 2019. A meta-analysis was conducted using RevMan 5.3 and Stata 12.0 software. We compared the effects of vitamin D supplementation alone to the administration of placebos on metabolic parameters of PCOS women with vitamin D deficiency. RESULTS Ten articles of RCTs were included and analyzed in this meta-analysis, which included a total of 520 PCOS women. Our meta-analysis results showed no significant effects of vitamin D supplementation on BMI (p = .43), systolic blood pressure (p = .05), diastolic blood pressure (p = .87), fasting insulin concentration (p = .86), HOMA-IR (p = .47), HDL-C (p = .76), LDL-C (p = .23) and triglyceride (p = .77). Both low dose vitamin D supplementation (<4000 IU/day) and high dose vitamin D supplementation (≥4000 IU/day) were found to significantly decreased the fasting glucose concentration (p = .01, p = .001, respectively). Vitamin D supplementation significantly decreased total cholesterol concentration (p = .03). CONCLUSIONS The results of this meta-analysis suggested that vitamin D supplementation decreases fasting glucose concentration and total cholesterol concentration in PCOS women with vitamin D deficiency.
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10.
The effectiveness of coenzyme Q10, vitamin E, inositols, and vitamin D in improving the endocrine and metabolic profiles in women with polycystic ovary syndrome: a network Meta-analysis.
Zhang, J, Xing, C, Zhao, H, He, B
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(12):1063-1071
Abstract
OBJECTIVE This research evaluated the efficacy of oral nutritional agents including CoQ10, vitamin E, inositols and vitamin D on androgen-associated hormones, glycolipid metabolism and body weight in women with PCOS. METHOD A multi-database search was performed from inception to December 2020. Using multi-variate random effects method, a NMA was conducted by synthesizing data pooled from RCTs. It was registered with PROSPERO (registration number CRD42021230292). RESULTS Twenty-three RCTs and 1291 participants were included. Based on NMA, CoQ10, vitamin E, CoQ10 combined with vitamin E, and inositols were successful in decreasing TT as compared with PA; vitamin E was superior to other agents. Vitamin E and inositols were successful in increasing SHBG levels; inositols were stronger than vitamin E. CoQ10 alone or combined with vitamin E, and inositols were successful in decreasing HOMA-IR. Inositols had the best results among included nutraceuticals to ameliorate HOMA-IR, FBG, FINS, TG, TC, and LDL-C and correlated to improvements in BMI. There was no significant difference between the CoQ10 or vitamin E group and the PA group in ameliorating lipid metabolism, and vitamin D had no positive effects in ameliorating hyperandrogenism, BMI, glycolipid metabolism profiles compared with PA. CONCLUSION For women with PCOS, inositols supplementation have some certain advantages in increasing SHBG and improving glycolipid metabolism when compared with nutraceuticals like CoQ10, vitamin E, vitamin D. Besides, vitamin E may be a better option in reducing TT and increasing SHBG. CoQ10 alone or combined with vitamin E can be helpful in decreasing HOMA-IR as well.