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Seminars in Reproductive Medicine Dec 2012There appears to be an epidemic of both obesity and polycystic ovary syndrome (PCOS) in the world today. However, obesity per se is not a part of the phenotype in many... (Review)
Review
There appears to be an epidemic of both obesity and polycystic ovary syndrome (PCOS) in the world today. However, obesity per se is not a part of the phenotype in many parts of the world. Obesity is likely not a cause of PCOS, as the high prevalence of PCOS among relatively thin populations demonstrates. However, obesity does exacerbate many aspects of the phenotype, especially cardiovascular risk factors such as glucose intolerance and dyslipidemia. It is also associated with a poor response to infertility treatment and likely an increased risk for pregnancy complications in those women who do conceive. Although most treatments of obesity, with the exception of bariatric surgery, achieve modest reductions in weight and improvements in the PCOS phenotype, encouraging weight loss in the obese patient remains one of the front-line therapies. However, further studies are needed to identify the best treatments, and the role of lifestyle therapies in women of normal weight with PCOS is uncertain.
Topics: Female; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Obesity; Ovary; Polycystic Ovary Syndrome; Pregnancy; Reproduction
PubMed: 23074008
DOI: 10.1055/s-0032-1328878 -
Frontiers in Endocrinology 2023
Topics: Female; Humans; Polycystic Ovary Syndrome
PubMed: 37588987
DOI: 10.3389/fendo.2023.1247679 -
BMC Endocrine Disorders Apr 2023Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder with a variety of symptoms. Current treatment options include the contraceptive pill as well as... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder with a variety of symptoms. Current treatment options include the contraceptive pill as well as metformin, however both treatments are limited to specific symptoms and have common side effects.
METHODS
This phase IV study is a monocentric, double blinded randomized clinical trial comparing the effects of six months of probiotic intervention to a placebo, with an additional open-label metformin arm as a positive control in a total of 180 participants with PCOS. The first of three visits is the screening visit, where inclusion/exclusion criteria are assessed. At the first visit, they are randomised into one of the three treatment arms equally and receive their study medication. After six months, all assessments from the first two visits are repeated. The primary endpoint is the change in free testosterone levels after the intervention, while secondary endpoints include changes in hormonal and metabolic parameters associated with PCOS as well as the gut microbial composition and diversity after intervention.
DISCUSSION
Based on new insights into the role of the gut microbiome in PCOS development, this study is exploring the potential of using probiotics to treat women with PCOS symptoms. If successful, this new therapy approach could open a new realm of possibilities for treating PCOS. To our knowledge, this is the first study comparing probiotic intervention with not only placebo treatment, but also metformin. This study has been approved by the ethics committee of the Medical University of Graz (EC number 32-230 ex 19/20).
REGISTRATION
EudraCT number: 2020-000228-20.
CLINICALTRIALS
gov identifier: NCT04593459.
PROTOCOL VERSION
Version 1.5 dated 29th November 2021.
Topics: Humans; Female; Metformin; Polycystic Ovary Syndrome; Double-Blind Method; Probiotics
PubMed: 37062834
DOI: 10.1186/s12902-023-01294-6 -
Revista Da Associacao Medica Brasileira... 2015
Topics: Female; Humans; Insulin; Life Style; Polycystic Ovary Syndrome
PubMed: 26841154
DOI: 10.1590/1806-9282.61.06.485 -
Trends in Endocrinology and Metabolism:... Jan 2019Recent studies have shown that sex and sex steroids influence the composition of the gut microbiome. These studies also indicate that steroid regulation of the gut... (Review)
Review
Recent studies have shown that sex and sex steroids influence the composition of the gut microbiome. These studies also indicate that steroid regulation of the gut microbiome may play a role in pathological situations of hormonal excess, such as PCOS. Indeed, studies demonstrated that PCOS is associated with decreased alpha diversity and changes in specific Bacteroidetes and Firmicutes, previously associated with metabolic dysregulation. These studies suggest that androgens may regulate the gut microbiome in females and that hyperandrogenism may be linked with a gut 'dysbiosis' in PCOS. Future mechanistic studies will be required to elucidate how sex steroids regulate the composition and function of the gut microbial community and what the consequences of this regulation are for the host.
Topics: Dysbiosis; Female; Gastrointestinal Microbiome; Gonadal Steroid Hormones; Humans; Polycystic Ovary Syndrome
PubMed: 30503354
DOI: 10.1016/j.tem.2018.11.001 -
Fertility and Sterility May 2022Polycystic ovary syndrome (PCOS) impacts approximately 6%-10% of women worldwide, with hallmark features of hyperandrogenism, irregular menses, infertility, and... (Review)
Review
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.
Topics: Cardiovascular Diseases; Carotid Intima-Media Thickness; Female; Humans; Hyperandrogenism; Insulin Resistance; Male; Polycystic Ovary Syndrome; Risk Factors
PubMed: 35512975
DOI: 10.1016/j.fertnstert.2022.02.028 -
EBioMedicine Aug 2023
Topics: Female; Humans; Polycystic Ovary Syndrome
PubMed: 37567728
DOI: 10.1016/j.ebiom.2023.104754 -
Nutrients Jul 2023Polycystic ovary syndrome (PCOS) affects a considerable percentage of females of reproductive age. PCOS is an obesity-related condition and its effects are greatly... (Review)
Review
Polycystic ovary syndrome (PCOS) affects a considerable percentage of females of reproductive age. PCOS is an obesity-related condition and its effects are greatly amplified by obesity. Even though the pathogenesis of PCOS remains complex and has not been fully elucidated, a link between obesity, PCOS, and dysbiosis has been described. The potential role of the gut microbiota in the development and progression of PCOS and its associated symptoms has also been reported. The aim of this narrative review is to present a non-systematic analysis of the available literature on the topic of probiotics and PCOS in adolescents with obesity in order to revise the beneficial effects of probiotics/symbiotic supplementation on hormonal and metabolic profiles and inflammatory conditions. The effectiveness of probiotics/synbiotics in PCOS has been supported. The literature suggests that probiotic/symbiotic supplementation may ameliorate hormonal profiles, inflammatory indicators, and lipid metabolism disturbances caused by PCOS. Studies also show improvements in weight, BMI, insulin, and HOMA-IR, including a potential role it plays in protecting fertility. Even though further studies are needed to confirm these findings, particularly in adolescent patients, probiotic supplementation may be considered a solution for managing PCOS in adolescents with obesity.
Topics: Female; Adolescent; Humans; Polycystic Ovary Syndrome; Insulin Resistance; Pediatric Obesity; Insulin; Probiotics
PubMed: 37513562
DOI: 10.3390/nu15143144 -
PLoS Medicine Jun 2020Polycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive-age women worldwide, depending on the diagnostic criteria...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive-age women worldwide, depending on the diagnostic criteria applied. These diagnostic criteria are based on expert opinion and have been the subject of considerable controversy. The phenotypic variation observed in PCOS is suggestive of an underlying genetic heterogeneity, but a recent meta-analysis of European ancestry PCOS cases found that the genetic architecture of PCOS defined by different diagnostic criteria was generally similar, suggesting that the criteria do not identify biologically distinct disease subtypes. We performed this study to test the hypothesis that there are biologically relevant subtypes of PCOS.
METHODS AND FINDINGS
Using biochemical and genotype data from a previously published PCOS genome-wide association study (GWAS), we investigated whether there were reproducible phenotypic subtypes of PCOS with subtype-specific genetic associations. Unsupervised hierarchical cluster analysis was performed on quantitative anthropometric, reproductive, and metabolic traits in a genotyped cohort of 893 PCOS cases (median and interquartile range [IQR]: age = 28 [25-32], body mass index [BMI] = 35.4 [28.2-41.5]). The clusters were replicated in an independent, ungenotyped cohort of 263 PCOS cases (median and IQR: age = 28 [24-33], BMI = 35.7 [28.4-42.3]). The clustering revealed 2 distinct PCOS subtypes: a "reproductive" group (21%-23%), characterized by higher luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels with relatively low BMI and insulin levels, and a "metabolic" group (37%-39%), characterized by higher BMI, glucose, and insulin levels with lower SHBG and LH levels. We performed a GWAS on the genotyped cohort, limiting the cases to either the reproductive or metabolic subtypes. We identified alleles in 4 loci that were associated with the reproductive subtype at genome-wide significance (PRDM2/KAZN, P = 2.2 × 10-10; IQCA1, P = 2.8 × 10-9; BMPR1B/UNC5C, P = 9.7 × 10-9; CDH10, P = 1.2 × 10-8) and one locus that was significantly associated with the metabolic subtype (KCNH7/FIGN, P = 1.0 × 10-8). We developed a predictive model to classify a separate, family-based cohort of 73 women with PCOS (median and IQR: age = 28 [25-33], BMI = 34.3 [27.8-42.3]) and found that the subtypes tended to cluster in families and that carriers of previously reported rare variants in DENND1A, a gene that regulates androgen biosynthesis, were significantly more likely to have the reproductive subtype of PCOS. Limitations of our study were that only PCOS cases of European ancestry diagnosed by National Institutes of Health (NIH) criteria were included, the sample sizes for the subtype GWAS were small, and the GWAS findings were not replicated.
CONCLUSIONS
In conclusion, we have found reproducible reproductive and metabolic subtypes of PCOS. Furthermore, these subtypes were associated with novel, to our knowledge, susceptibility loci. Our results suggest that these subtypes are biologically relevant because they appear to have distinct genetic architecture. This study demonstrates how phenotypic subtyping can be used to gain additional insights from GWAS data.
Topics: Adult; Cluster Analysis; Female; Genetic Association Studies; Genome-Wide Association Study; Humans; Phenotype; Polycystic Ovary Syndrome
PubMed: 32574161
DOI: 10.1371/journal.pmed.1003132 -
Fertility and Sterility Mar 2023Polycystic ovary syndrome (PCOS) is a common endocrine disorder that impacts women worldwide. There are several racial and ethnic differences in PCOS phenotypes and in... (Review)
Review
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that impacts women worldwide. There are several racial and ethnic differences in PCOS phenotypes and in PCOS- associated metabolic dysfunction. In this review, we summarize the current literature on disparities in the diagnosis and outcomes associated with PCOS in the United States. Future studies are needed to address gaps in knowledge for racial and ethnic-specific differences in PCOS, and include a large number of non-White and/or Hispanic participants in PCOS studies.
Topics: Female; Humans; Phenotype; Polycystic Ovary Syndrome; Racial Groups; United States; Health Status Disparities
PubMed: 36702345
DOI: 10.1016/j.fertnstert.2023.01.031