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Women's Health (London, England) 2024Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including... (Review)
Review
Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including hyperandrogenism, chronic anovulation, and polycystic ovaries. In addition, half of women with polycystic ovary syndrome have insulin resistance, and obesity or overweight, type 2 diabetes, hypertension, and hyperlipidemia are the most common metabolic abnormalities affecting (30%) women with polycystic ovary syndrome. Weight loss is regarded as the first-line treatment as it can potentially improve polycystic ovary syndrome parameters (androgen levels, menstrual cyclicity, lipid and glucose metabolism). However, achieving and maintaining weight loss can be challenging, and pharmacological agents could be essential to achieve optimal glycemic control and improve the endocrine disturbance associated with polycystic ovary syndrome. Glucagon-like peptide-1 receptor agonist has been demonstrated as monotherapy or in combination with metformin for managing obesity and insulin resistance associated with polycystic ovary syndrome. Yet, its effect on endocrine and metabolic parameters remains elusive, and further research is needed to close the gap. The aim is to evaluate the efficacy of glucagon-like peptide-1 receptor agonist monotherapy and/or a combined treatment between glucagon-like peptide-1 receptor agonist and metformin for improving anthropometric measurements, endocrine and metabolic parameters in lean and obese women with polycystic ovary syndrome. A systematic review of longitudinal cohort studies was conducted across databases including Ovid Medline, PubMed Central, and Cochrane Library between 2015 and 2022. Eligible studies included participants with polycystic ovary syndrome diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health criteria. A total of eight studies including 486 patients with polycystic ovary syndrome were analyzed. The mean age was between 18 and 45 years with mean follow-up period between 12 and 32 weeks. In all these studies, results were comparable for the reduction in body mass index, waist circumference, fat mass, and visceral fat mass; however, it was more in combination therapy versus comparator. In conclusion, glucagon-like peptide-1 receptor agonists effectively reduce body weight and improve some of the endocrine and metabolic parameters of polycystic ovary syndrome. A combined treatment with glucagon-like peptide-1 receptor agonist and metformin had significant effects on weight loss and favorable results on endocrine and metabolic parameters, yet further research is needed to discover the long-term safety of combined therapy in women diagnosed with polycystic ovary syndrome and obesity or overweight.
Topics: Female; Humans; Infant; Male; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor Agonists; Insulin Resistance; Longitudinal Studies; Metformin; Obesity; Overweight; Polycystic Ovary Syndrome; United States; Weight Loss
PubMed: 38444070
DOI: 10.1177/17455057241234530 -
Scientific Reports Mar 2024Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between...
Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28-1.59; P = 6.66 × 10), ovarian cysts (OR = 1.36, 95% CI 1.20-1.55; P = 1.57 × 10), AUB (OR = 1.41, 95% CI 1.20-1.66; P = 3.01 × 10), and endometriosis (OR = 1.43, 95% CI 1.27-1.70; P = 2.21 × 10) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.
Topics: Pregnancy; Female; Humans; Polycystic Ovary Syndrome; Depression; Dysthymic Disorder; Endometriosis; Mendelian Randomization Analysis; Ovarian Cysts; Genome-Wide Association Study
PubMed: 38472314
DOI: 10.1038/s41598-024-55993-8 -
Frontiers in Endocrinology 2024Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is...
BACKGROUND
Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted.
METHODS
Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses.
RESULTS
The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS.
CONCLUSIONS
Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Genome-Wide Association Study; Mendelian Randomization Analysis; Hyperthyroidism
PubMed: 38586452
DOI: 10.3389/fendo.2024.1364157 -
Bioscience Trends Jan 2024Microorganisms are ubiquitous in the human body; they are present in various areas including the gut, mouth, skin, respiratory tract, and reproductive tract. The... (Review)
Review
Microorganisms are ubiquitous in the human body; they are present in various areas including the gut, mouth, skin, respiratory tract, and reproductive tract. The interaction between the microbiome and reproductive health has become an increasingly compelling area of study. Disruption of the female genital tract microbiome can significantly impact the metabolism of amino acids, carbohydrates, and lipids, increasing susceptibility to reproductive tract diseases such as vaginitis, chronic endometritis, endometrial polyps, endometriosis, and polycystic ovary syndrome. The gut microbiome, considered an endocrine organ, plays a crucial role in the reproductive endocrine system by interacting with hormones like estrogen and androgens. Imbalances in the gut microbiome composition can lead to various diseases and conditions, including polycystic ovary syndrome, endometriosis, and cancer, although research on their mechanisms remains limited. This review highlights the latest advancements in understanding the female genital tract and gut microbiomes in gynecological diseases. It also explores the potential of microbial communities in the treatment of reproductive diseases. Future research should focus on identifying the molecular mechanisms underlying the association between the microbiome and reproductive diseases to develop new and effective strategies for disease prevention, diagnosis, and treatment related to female reproductive organs.
Topics: Female; Humans; Gastrointestinal Microbiome; Polycystic Ovary Syndrome; Endometriosis; Genitalia, Female; Reproduction
PubMed: 38104979
DOI: 10.5582/bst.2023.01133 -
Gynecological Endocrinology : the... Dec 2024In this article, we present a narrative review on the use of inositol in the treatment of polycystic ovary syndrome (PCOS). Of the different inositols that exist, only... (Review)
Review
In this article, we present a narrative review on the use of inositol in the treatment of polycystic ovary syndrome (PCOS). Of the different inositols that exist, only myo-inositol (MYO) and D-chiro inositol (DCI) have been studied in the treatment of PCOS. The results of the studies show that there is insufficient or controversial evidence to recommend the use of DCI alone, while MYO alone shows positive results and, above all, the MYO/DCI combination is effective when used at a ratio of at least 40:1, but there is enough rationale to further study ratios such as 66:1 to 100:1 as other possible effective combinations.
Topics: Female; Humans; Inositol; Polycystic Ovary Syndrome
PubMed: 38239032
DOI: 10.1080/09513590.2023.2301554 -
Journal of Obstetrics and Gynaecology :... Dec 2024Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and haemostatic sealant) on ovarian reserve in patients with ovarian cysts are not well known.
METHODS
The Cochrane Library, PubMed and Web of Science databases were searched from the date of inception of the database to June 2022 for literature exploring the impact of haemostasis methods during ovarian cystectomy on ovarian reserve. A traditional meta-analysis was performed using Review Manager software. A network meta-analysis (NMA) was performed using Stata and GemTC software.
RESULTS
The direct meta-analysis comparison indicated that the mean postoperative reduction of anti-Müllerian hormone (AMH) level was significantly higher in the electrocoagulation (bipolar) group than suture and haemostatic sealant group, both in the overall group and subgroup of women with ovarian endometrioma. In NMA, the reduction of postoperative AMH levels in the electrocoagulation (bipolar) group was higher than the suture group at 6 months with a statistical significance, and at 1, 3 and 12 months without a significant difference. The difference in the postoperative decrease of AMH level did not reach statistical significance between suture and sealant, coagulation and haemostatic sealant. The comprehensive ranking results revealed that suture treatment was, with the highest probability, beneficial to the protection of the ovarian reserve.
CONCLUSIONS
There was insufficient research to detect the optimal haemostasis method for ovarian reserve preservation in ovarian cystectomy. Nevertheless, haemostasis by electrocoagulation (bipolar) should be avoided when possible, and the suture might be considered as the best choice.
Topics: Humans; Female; Ovarian Reserve; Cystectomy; Network Meta-Analysis; Laparoscopy; Ovarian Cysts; Hemostatics; Hemostasis; Anti-Mullerian Hormone; Endometriosis
PubMed: 38406841
DOI: 10.1080/01443615.2024.2320294 -
Scientific Reports Sep 2023Obesity has harmful consequences on reproductive outcomes and the rapid increase in obesity is assumed to be influenced by epigenetics and trans-generation effects. Our...
Obesity has harmful consequences on reproductive outcomes and the rapid increase in obesity is assumed to be influenced by epigenetics and trans-generation effects. Our study aimed to explore the effect of maternal and/or paternal obesity on the ovarian tissues of the first-generation female offspring in rats. The study was conducted on 40 adult Wistar albino rats (20 males and 20 females). Obesity was induced by feeding them an obesogenic diet for 3 months. The pregnancy was induced in the females by mating with males in four combinations: healthy mother with healthy father (control parents, CP), healthy mother with obese fathers (OF), obese mothers with healthy father (OM), and obese mother with obese father (obese parents, OP). After delivery, the female offspring at two months were sacrificed, and the blood and ovarian tissues were collected to assess the studied parameters. Our result showed differential impacts of maternal and paternal obesity on the ovarian health of the female offspring. The female offspring of obese OM or OP showed early signs of obesity. These metabolic abnormalities were associated with signs of ovarian lesions, impaired folliculogenesis, and decreased oocyte quality and also showed significant alterations in mitochondrial biogenesis, redox status, inflammation, and microRNAs expression (miR-149 and miR-494). In conclusion, altered ovarian expression of microRNAs and associated impaired mitochondrial biogenesis pathways may be the root causes for the observed intergeneration transmission of the obesogenic phenotype.
Topics: Female; Male; Pregnancy; Humans; Rats; Animals; Organelle Biogenesis; Ovarian Cysts; Rats, Wistar; Ovarian Neoplasms; Obesity; MicroRNAs; Fathers
PubMed: 37726284
DOI: 10.1038/s41598-023-42468-5 -
Reproductive Biology and Endocrinology... Nov 2023Polycystic ovary syndrome (PCOS) is a heterogeneous functional endocrine disorder associated with a low-grade, chronic inflammatory state. Patients with PCOS present an... (Review)
Review
Polycystic ovary syndrome (PCOS) is a heterogeneous functional endocrine disorder associated with a low-grade, chronic inflammatory state. Patients with PCOS present an increased risk of metabolic comorbidities and often menstrual dysregulation and infertility due to anovulation and/or poor oocyte quality. Multiple mechanisms including oxidative stress and low-grade inflammation are believed to be responsible for oocyte deterioration; however, the influence of nitric oxide (NO) insufficiency in oocyte quality and ovulatory dysfunction in PCOS is still a matter for debate. Higher production of superoxide (O) mediated DNA damage and impaired antioxidant defense have been implicated as contributory factors for the development of PCOS, with reported alteration in superoxide dismutase (SOD) function, an imbalanced zinc/copper ratio, and increased catalase activity. These events may result in decreased hydrogen peroxide (HO) accumulation with increased lipid peroxidation events. A decrease in NO, potentially due to increased activity of NO synthase (NOS) inhibitors such as asymmetric dimethylarginine (ADMA), and imbalance in the distribution of reactive oxygen species (ROS), such as decreased HO and increased O, may offset the physiological processes surrounding follicular development, oocyte maturation, and ovulation contributing to the reproductive dysfunction in patients with PCOS. Thus, this proposal aims to evaluate the specific roles of NO, oxidative stress, ROS, and enzymatic and nonenzymatic elements in the pathogenesis of PCOS ovarian dysfunction, including oligo- anovulation and oocyte quality, with the intent to inspire better application of therapeutic options. The authors believe more consideration into the specific roles of oxidative stress, ROS, and enzymatic and nonenzymatic elements may allow for a more thorough understanding of PCOS. Future efforts elaborating on the role of NO in the preoptic nucleus to determine its influence on GnRH firing and follicle-stimulating hormone/Luteinizing hormone (FSH/LH) production with ovulation would be of benefit in PCOS. Consequently, treatment with an ADMA inhibitor or NO donor may prove beneficial to PCOS patients experiencing reproductive dysfunction and infertility.
Topics: Female; Humans; Polycystic Ovary Syndrome; Luteinizing Hormone; Anovulation; Nitric Oxide; Follicle Stimulating Hormone; Reactive Oxygen Species; Hydrogen Peroxide; Infertility; Oxidative Stress
PubMed: 37996893
DOI: 10.1186/s12958-023-01159-6 -
Endocrine Sep 2023Polycystic ovarian syndrome (PCOS) is a common heterogeneous condition with probably multifactorial genesis. Animal studies have proven the essential role of the...
PURPOSE
Polycystic ovarian syndrome (PCOS) is a common heterogeneous condition with probably multifactorial genesis. Animal studies have proven the essential role of the sympathetic nervous system in the syndrome development, while human studies are still contradictory. The present study aims to investigate the possible influence of plasma-free metanephrine (MN), and normetanephrine (NMN), nerve growth factor (NGF), and renalase (RNL) on the hormonal and metabolic parameters in women with PCOS and healthy controls.
METHODS
Fifty patients with PCOS and 30 healthy women participated in the study. The plasma-free MN and NMN, NGF, RNL, anti-Mullerian hormone (AMH), gonadotropin, androgen levels, and metabolic parameters were investigated.
RESULTS
Plasma-free NMN and NGF concentrations were increased in PCOS individuals, while RNL levels were decreased compared to healthy volunteers. Increased plasma-free NMN (OR = 1.0213 [95%CI 1.0064-1.0364], p = 0.005) and NGF (OR = 1.0078 [95%CI 1.0001-1.0155], p = 0.046) but not MN or RNL levels were associated with a higher risk of PCOS after adjustment for age. Plasma-free NMN levels were positively associated with the LH (r = +0.253; p = 0.039). androstenedione (r = +0.265; p = 0.029), 17-OH progesterone (r = +0.285; p = 0.024), NGF (r = +0.320; p = 0.008), and AMH (r = +0.417; p < 0.001) concentrations of the investigated women. RNL levels were inversely related to the BMI (r = -0.245; p = 0.029), HOMA-IR (r = -0.250; p = 0.030), free testosterone (r = -0.303; p = 0.006) levels. systolic (r = -0.294; p = 0.008) and diastolic (r = -0.342; p = 0.002) blood pressure.
CONCLUSIONS
Increased sympathetic noradrenergic activity and NGF synthesis might be related to the increased AMH and delta-4 androgen levels in a subgroup of PCOS patients. RNL levels might influence the metabolic status of PCOS patients. Further studies are needed to explore the significance of adrenal medullar and autonomic dysfunction for developing different PCOS phenotypes and their subsequent cardiovascular complications.
Topics: Humans; Female; Polycystic Ovary Syndrome; Metanephrine; Androgens; Nerve Growth Factor; Anti-Mullerian Hormone
PubMed: 37248367
DOI: 10.1007/s12020-023-03404-9 -
Human Genomics Nov 2023Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain.
METHODS
We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.
RESULTS
Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis.
CONCLUSION
This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary.
Topics: Female; Humans; Biopsy; Diabetes Mellitus, Type 1; Eye; Genome-Wide Association Study; Polycystic Ovary Syndrome; Mendelian Randomization Analysis
PubMed: 37957681
DOI: 10.1186/s40246-023-00550-z