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1.
Cytokine ; 179: 156639, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38733946

ABSTRACT

AIMS: Polycystic ovarian syndrome (PCOS) is one of the most common (about 5-20%) reproductive disorders in women of reproductive age; it is characterized by polycystic ovaries, hyperandrogenism, and oligo/ anovulation. The levels and expression of ovarian adipokines are deregulated in the PCOS. Apelin is an adipokine that acts through its receptor (APJ) and is known to express in the various tissues including the ovary. It has also been suggested that apelin and APJ could be targeted as therapeutic adjuncts for the management of PCOS. However, no study has been conducted on the management of PCOS by targeting the apelin system. Thus, we aimed to evaluate its impact on combating PCOS-associated ovarian pathogenesis. METHODS: The current work employed a letrozole-induced-hyperandrogenism PCOS-like mice model to investigate the effects of apelin13 and APJ, antagonist ML221. The PCOS model was induced by oral administration of letrozole (1 mg/kg) for 21 days. A total of four experimental groups were made, control, PCOS control, PCOS + aplein13, and PCOS + ML221. The treatment of apelin13 and ML221 was given from day 22 for two weeks. KEY FINDINGS: The letrozole-induced PCOS-like features such as hyperandrogenism, cystic follicle, decreased corpus luteum, elevated levels of LH/FSH ratio, and up-regulation of ovarian AR expression were ameliorated by apelin13 and ML221 treatment. However, the PCOS-augmented oxidative stress and apoptosis were suppressed by apelin 13 treatments only. ML221 treatment still showed elevated oxidative stress and stimulated apoptosis as reflected by decreased antioxidant enzymes and increased active caspase3 and Bax expression. The expression of ERs was elevated in all groups except control. Furthermore, the PCOS model showed elevated expression of APJ and apelin13 treatment down-regulated its own receptor. Overall, observing the ovarian histology, corpus luteum formation, and decreased androgen levels by both apelin13 and ML221 showed ameliorative effects on the cystic ovary. SIGNIFICANCE: Despite the similar morphological observation of ovarian histology, apelin13 and ML221 exhibited opposite effects on oxidative stress and apoptosis. Therefore, apelin13 (which down-regulates APJ) and ML221 (an APJ antagonist) may have suppressed APJ signalling, which would account for our findings on the mitigation of polycystic ovarian syndrome. In conclusion, both apelin13 and ML221 mediated mitigation have different mechanisms, which need further investigation.


Subject(s)
Apelin Receptors , Apelin , Letrozole , Ovary , Polycystic Ovary Syndrome , Letrozole/pharmacology , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/drug therapy , Animals , Female , Apelin Receptors/metabolism , Mice , Apelin/metabolism , Ovary/metabolism , Ovary/pathology , Ovary/drug effects , Oxidative Stress/drug effects , Hyperandrogenism/metabolism , Hyperandrogenism/chemically induced , Apoptosis/drug effects , Disease Models, Animal
2.
J Ovarian Res ; 17(1): 105, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760835

ABSTRACT

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.


Subject(s)
Fertilization in Vitro , Infertility, Female , Ovulation Induction , Humans , Female , Infertility, Female/metabolism , Infertility, Female/blood , Adult , Ovarian Hyperstimulation Syndrome/blood , Ovarian Hyperstimulation Syndrome/metabolism , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/complications , Gas Chromatography-Mass Spectrometry , Metabolome , Metabolomics/methods , Pregnancy , Ovary/metabolism
3.
J Ovarian Res ; 17(1): 106, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762718

ABSTRACT

BACKGROUND: Epidemiological studies regarding the correlation between anti-Müllerian hormone (AMH) and insulin resistance (IR) in polycystic ovarian syndrome (PCOS) remain inconsistent. The primary aim of this study was to determine the correlations between AMH and IR in patients with PCOS and to explore the selected factors that influence the correlations. METHODS: We conducted systemic searches of online databases (PubMed, Science Direct, Taylor and Francis, Scopus, and ProQuest) from inception to December 20, 2023 and manual searches of the associated bibliographies to identify relevant studies. We then performed subgroup and sensitivity analyses to explore the sources of heterogeneity, followed by a publication bias risk assessment of the included studies using the Joanna Briggs Institute critical appraisal tool. We used a random-effects model to estimate the pooled correlations between AMH and the homeostatic model assessment for insulin resistance (HOMA-IR) in patients with polycystic ovarian syndrome (PCOS). RESULTS: Of the 4835 articles identified, 22 eligible relevant studies from three regions were included and identified as low risk of bias. The random-effects pooled correlation estimate was 0.089 (95% confidence interval [CI]: -0.040, 0.215), with substantial heterogeneity (I2 = 87%; τ2 = 0.0475, p < .001). Subgroup analyses showed that the study region did not influence the correlation estimates, and sensitivity analysis showed no significant alteration in the pooled correlation estimate or 95% CI values. No publication bias was observed. CONCLUSION: There was a weak, statistically insignificant correlation between AMH and HOMA-IR in patients with PCOS. The correlation estimates did not vary according to the study participants' regions.


Subject(s)
Anti-Mullerian Hormone , Insulin Resistance , Polycystic Ovary Syndrome , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/metabolism , Humans , Anti-Mullerian Hormone/blood , Female
4.
Front Endocrinol (Lausanne) ; 15: 1331282, 2024.
Article in English | MEDLINE | ID: mdl-38774232

ABSTRACT

Introduction: Polycystic ovary syndrome (PCOS) is a common multifactorial and polygenic disorder of the endocrine system, affecting up to 20% of women in reproductive age with a still unknown etiology. Follicular fluid (FF) represents an environment for the normal development of follicles rich in metabolites, hormones and neurotransmitters, but in some instances of PCOS the composition can be different. Vasoactive intestinal peptide (VIP) is an endogenous autonomic neuropeptide involved in follicular atresia, granulosa cell physiology and steroidogenesis. Methods: ELISA assays were performed to measure VIP and estradiol levels in human follicular fluids, while AMH, FSH, LH, estradiol and progesterone in the plasma were quantified by chemiluminescence. UHPLC/QTOF was used to perform the untargeted metabolomic analysis. Results: Our ELISA and metabolomic results show: i) an increased concentration of VIP in follicular fluid of PCOS patients (n=9) of about 30% with respect to control group (n=10) (132 ± 28 pg/ml versus 103 ± 26 pg/ml, p=0,03) in women undergoing in vitro fertilization (IVF), ii) a linear positive correlation (p=0.05, r=0.45) between VIP concentration and serum Anti-Müllerian Hormone (AMH) concentration and iii) a linear negative correlation between VIP and noradrenaline metabolism. No correlation between VIP and estradiol (E2) concentration in follicular fluid was found. A negative correlation was found between VIP and noradrenaline metabolite 3,4-dihydroxyphenylglycolaldehyde (DOPGAL) in follicular fluids. Conclusion: VIP concentration in follicular fluids was increased in PCOS patients and a correlation was found with noradrenaline metabolism indicating a possible dysregulation of the sympathetic reflex in the ovarian follicles. The functional role of VIP as noradrenergic modulator in ovarian physiology and PCOS pathophysiology was discussed.


Subject(s)
Fertilization in Vitro , Follicular Fluid , Polycystic Ovary Syndrome , Vasoactive Intestinal Peptide , Humans , Female , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/blood , Vasoactive Intestinal Peptide/metabolism , Vasoactive Intestinal Peptide/blood , Follicular Fluid/metabolism , Adult , Estradiol/blood , Estradiol/metabolism , Anti-Mullerian Hormone/blood , Anti-Mullerian Hormone/metabolism , Case-Control Studies
5.
Mol Biol Rep ; 51(1): 631, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722405

ABSTRACT

Adipokines are now well-known to regulate reproduction. Visfatin is an adipokine expressed in the hypothalamus, pituitary, ovary, uterus, and placenta of different species, and since it has been found to modulate the endocrine secretion of the hypothalamus, pituitary gland and ovary, it may be considered a novel regulator of female reproduction. Although the majority of the literature explored its role in ovarian regulation, visfatin has also been shown to regulate uterine remodeling, endometrial receptivity and embryo development, and its expression in the uterus is steroid dependent. Like other adipokines, visfatin expression and levels are deregulated in pathological conditions including polycystic ovary syndrome. Thus, the present mini-review focuses on the role of visfatin in female reproduction under both physiological and pathological conditions.


Subject(s)
Nicotinamide Phosphoribosyltransferase , Polycystic Ovary Syndrome , Reproduction , Female , Humans , Nicotinamide Phosphoribosyltransferase/metabolism , Nicotinamide Phosphoribosyltransferase/genetics , Reproduction/physiology , Reproduction/genetics , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/physiopathology , Animals , Ovary/metabolism , Uterus/metabolism , Cytokines/metabolism , Pregnancy , Adipokines/metabolism
6.
Food Res Int ; 186: 114338, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729719

ABSTRACT

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.


Subject(s)
Fasting , Glucagon-Like Peptide 2 , Obesity , Permeability , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/metabolism , Female , Adult , Fasting/blood , Male , Glucagon-Like Peptide 2/blood , Intestinal Mucosa/metabolism , Gastrointestinal Microbiome , Nutrients , Young Adult , Haptoglobins/metabolism , Endotoxemia , Lipopolysaccharide Receptors/blood , Acute-Phase Proteins/metabolism , Biomarkers/blood , Membrane Glycoproteins/blood , Membrane Glycoproteins/metabolism , Dietary Fats , Glucose/metabolism , Intestinal Barrier Function , Carrier Proteins , Protein Precursors
7.
Rev Assoc Med Bras (1992) ; 70(4): e20231368, 2024.
Article in English | MEDLINE | ID: mdl-38716947

ABSTRACT

OBJECTIVE: The study evaluated the opinions of polycystic ovary syndrome on the life quality of women. METHODS: A total of 249 women with polycystic ovary syndrome participated in this descriptive study between October 2022 and July 2023 in Istanbul, Turkey. FINDINGS: Polycystic Ovary Syndrome and Quality of Life was significantly correlated with age (p=0.000) and frequent weight loss diets (p=0.000) (p<0.01). Among the Polycystic Ovary Syndrome and Quality of Life total score and polycystic ovary syndrome symptoms, those with hormone imbalance and insulin resistance had the highest mean scores, while those with menstrual irregularity and fatigue had the lowest. CONCLUSION: Advancing age changes the quality of life of women with polycystic ovary syndrome. To prevent the negative impact of polycystic ovary syndrome on women's quality of life, it is recommended that health professionals develop effective care plans utilizing available evidence.


Subject(s)
Polycystic Ovary Syndrome , Quality of Life , Humans , Polycystic Ovary Syndrome/psychology , Polycystic Ovary Syndrome/physiopathology , Polycystic Ovary Syndrome/complications , Female , Adult , Young Adult , Turkey , Surveys and Questionnaires , Adolescent , Age Factors , Insulin Resistance/physiology , Body Mass Index
8.
J Ovarian Res ; 17(1): 95, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715063

ABSTRACT

BACKGROUND: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Polycystic Ovary Syndrome , Vitamin D , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/blood , Humans , Female , Vitamin D/blood , Polymorphism, Single Nucleotide , Testosterone/blood , Genetic Predisposition to Disease , Vitamin D Deficiency/genetics , Vitamin D Deficiency/complications , Vitamin D Deficiency/blood
9.
JAMA Netw Open ; 7(5): e249657, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38700861

ABSTRACT

Importance: Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions. Objective: To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions. Design, Setting, and Participants: This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys. Exposures: Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles. Main Outcomes and Measures: The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated. Results: The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity. Conclusions and Relevance: These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.


Subject(s)
Polycystic Ovary Syndrome , Humans , Female , Polycystic Ovary Syndrome/epidemiology , Polycystic Ovary Syndrome/complications , Cross-Sectional Studies , Adult , Menstruation Disturbances/epidemiology , United States/epidemiology , Cardiovascular Diseases/epidemiology , Young Adult , Cohort Studies , Middle Aged , Obesity/epidemiology , Adolescent , Alabama/epidemiology
10.
Am J Reprod Immunol ; 91(5): e13854, 2024 May.
Article in English | MEDLINE | ID: mdl-38716832

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder characterized by oligo-anovulation, hyperandrogenism, and polycystic ovaries, with hyperandrogenism being the most prominent feature of PCOS patients. However, whether excessive androgens also exist in the ovarian microenvironment of patients with PCOS, and their modulatory role on ovarian immune homeostasis and ovarian function, is not clear. METHODS: Follicular fluid samples from patients participating in their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment were collected. Androgen concentration of follicular fluid was assayed by chemiluminescence, and the macrophage M1:M2 ratio was detected by flow cytometry. In an in vitro model, we examined the regulatory effects of different concentrations of androgen on macrophage differentiation and glucose metabolism levels using qRT-PCR, Simple Western and multi-factor flow cytometry assay. In a co-culture model, we assessed the effect of a hyperandrogenic environment in the presence or absence of macrophages on the function of granulosa cells using qRT-PCR, Simple Western, EdU assay, cell cycle assay, and multi-factor flow cytometry assay. RESULTS: The results showed that a significantly higher androgen level and M1:M2 ratio in the follicular fluid of PCOS patients with hyperandrogenism. The hyperandrogenic environment promoted the expression of pro-inflammatory and glycolysis-related molecules and inhibited the expression of anti-inflammatory and oxidative phosphorylation-related molecules in macrophages. In the presence of macrophages, a hyperandrogenic environment significantly downregulated the function of granulosa cells. CONCLUSION: There is a hyperandrogenic microenvironment in the ovary of PCOS patients with hyperandrogenism. Hyperandrogenic microenvironment can promote the activation of ovarian macrophages to M1, which may be associated with the reprogramming of macrophage glucose metabolism. The increased secretion of pro-inflammatory cytokines by macrophages in the hyperandrogenic microenvironment would impair the normal function of granulosa cells and interfere with normal ovarian follicle growth and development.


Subject(s)
Androgens , Follicular Fluid , Granulosa Cells , Hyperandrogenism , Macrophages , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/immunology , Female , Granulosa Cells/metabolism , Macrophages/immunology , Macrophages/metabolism , Hyperandrogenism/metabolism , Adult , Follicular Fluid/metabolism , Androgens/metabolism , Cells, Cultured , Macrophage Activation , Cellular Microenvironment , Coculture Techniques , Cell Differentiation
11.
Croat Med J ; 65(2): 138-145, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38706239

ABSTRACT

AIM: To investigate the factors affecting metformin concentrations after chronic administration in patients with polycystic ovary syndrome (PCOS), focusing on the pharmacokinetic variability and its implications for personalized therapy. METHODS: This study enrolled 53 PCOS patients undergoing long-term metformin treatment at the Clinic for Gynecology and Obstetrics in Nis, Serbia, from February to December 2019. Pharmacokinetic parameters were measured from blood samples, and metformin concentrations were determined with validated analytical techniques. RESULTS: There was a significant variability in metformin concentrations among PCOS patients, with body mass index (BMI) identified as a major influencing factor. Higher BMI was associated with lower plasma metformin levels, a finding suggesting an altered pharmacokinetic profile in obese patients. CONCLUSIONS: This study highlights the critical role of BMI in influencing metformin pharmacokinetics in PCOS patients and underscores the need for personalized treatment strategies in patients with PCOS.


Subject(s)
Body Mass Index , Hypoglycemic Agents , Metformin , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/blood , Metformin/pharmacokinetics , Metformin/blood , Metformin/administration & dosage , Metformin/therapeutic use , Female , Adult , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/blood , Hypoglycemic Agents/therapeutic use , Serbia , Young Adult , Obesity
12.
BMC Microbiol ; 24(1): 169, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760705

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrinopathy in childbearing-age females which can cause many complications, such as diabetes, obesity, and dyslipidemia. The metabolic disorders in patients with PCOS were linked to gut microbial dysbiosis. However, the correlation between the gut microbial community and dyslipidemia in PCOS remains unillustrated. Our study elucidated the different gut microbiota in patients with PCOS and dyslipidemia (PCOS.D) compared to those with only PCOS and healthy women. RESULTS: In total, 18 patients with PCOS, 16 healthy females, and 18 patients with PCOS.D were enrolled. The 16 S rRNA sequencing in V3-V4 region was utilized for identifying the gut microbiota, which analyzes species annotation, community diversity, and community functions. Our results showed that the ß diversity of gut microbiota did not differ significantly among the three groups. Regarding gut microbiota dysbiosis, patients with PCOS showed a decreased abundance of Proteobacteria, and patients with PCOS.D showed an increased abundance of Bacteroidota compared to other groups. With respect to the gut microbial imbalance at genus level, the PCOS.D group showed a higher abundance of Clostridium_sensu_stricto_1 compared to other two groups. Furthermore, the abundances of Faecalibacterium and Holdemanella were lower in the PCOS.D than those in the PCOS group. Several genera, including Faecalibacterium and Holdemanella, were negatively correlated with the lipid profiles. Pseudomonas was negatively correlated with luteinizing hormone levels. Using PICRUSt analysis, the gut microbiota community functions suggested that certain metabolic pathways (e.g., amino acids, glycolysis, and lipid) were altered in PCOS.D patients as compared to those in PCOS patients. CONCLUSIONS: The gut microbiota characterizations in patients with PCOS.D differ from those in patients with PCOS and controls, and those might also be related to clinical parameters. This may have the potential to become an alternative therapy to regulate the clinical lipid levels of patients with PCOS in the future.


Subject(s)
Bacteria , Dysbiosis , Dyslipidemias , Gastrointestinal Microbiome , Polycystic Ovary Syndrome , RNA, Ribosomal, 16S , Humans , Polycystic Ovary Syndrome/microbiology , Female , Dyslipidemias/microbiology , Adult , Dysbiosis/microbiology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , RNA, Ribosomal, 16S/genetics , Young Adult , Feces/microbiology
13.
Sci Rep ; 14(1): 11689, 2024 05 22.
Article in English | MEDLINE | ID: mdl-38778076

ABSTRACT

We evaluated whether serum stem cell factor (s-SCF) levels just prior to ovulation induction could indicate the ability to develop a top-quality (TQ) blastocyst by day 5. We investigated patients with normal ovarian reserve (NOR), polycystic ovary syndrome (PCOS), diminished ovarian reserve (DOR), or mild endometriosis. Our pilot research suggests a correlation between s-SCF levels and the ability to form TQ blastocysts in patients with mild endometriosis. This significant statistical difference (p < 0.05) was noted between mild endometriosis patients for whom a TQ blastocyst was obtained and those for whom it was not possible, as measured on the 8th day of stimulation and the day of oocyte retrieval. The mean SCF levels in the serum of these women on the 8th day were at 28.07 (± 2.67) pg/ml for the TQ subgroup and 53.32 (± 16.02) pg/ml for the non-TQ subgroup (p < 0.05). On oocyte retrieval day it was 33.47 (± 3.93) pg/ml and 52.23 (± 9.72) pg/ml (p < 0.05), respectively.


Subject(s)
Blastocyst , Ovarian Reserve , Stem Cell Factor , Humans , Female , Stem Cell Factor/blood , Adult , Blastocyst/cytology , Ovarian Reserve/physiology , Polycystic Ovary Syndrome/blood , Endometriosis/blood , Oocyte Retrieval , Ovulation Induction/methods , Pilot Projects , Fertilization in Vitro/methods
14.
Front Endocrinol (Lausanne) ; 15: 1348368, 2024.
Article in English | MEDLINE | ID: mdl-38779450

ABSTRACT

Background: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. Conclusion: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.


Subject(s)
Mendelian Randomization Analysis , Polycystic Ovary Syndrome , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/epidemiology , Humans , Female , Risk Factors , Body Mass Index , Insulin Resistance
15.
Molecules ; 29(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38731586

ABSTRACT

Nanomedicine has revolutionized drug delivery in the last two decades. Nanoparticles appear to be a promising drug delivery platform in the treatment of various gynecological disorders including uterine leiomyoma, endometriosis, polycystic ovarian syndrome (PCOS), and menopause. Nanoparticles are tiny (mean size < 1000 nm), biodegradable, biocompatible, non-toxic, safe, and relatively inexpensive materials commonly used in imaging and the drug delivery of various therapeutics, such as chemotherapeutics, small molecule inhibitors, immune mediators, protein peptides and non-coding RNA. We performed a literature review of published studies to examine the role of nanoparticles in treating uterine leiomyoma, endometriosis, PCOS, and menopause. In uterine leiomyoma, nanoparticles containing 2-methoxyestradiole and simvastatin, promising uterine fibroid treatments, have been effective in significantly inhibiting tumor growth compared to controls in in vivo mouse models with patient-derived leiomyoma xenografts. Nanoparticles have also shown efficacy in delivering magnetic hyperthermia to ablate endometriotic tissue. Moreover, nanoparticles can be used to deliver hormones and have shown efficacy as a mechanism for transdermal hormone replacement therapy in individuals with menopause. In this review, we aim to summarize research findings and report the efficacy of nanoparticles and nanotherapeutics in the treatment of various benign gynecologic conditions.


Subject(s)
Genital Diseases, Female , Nanomedicine , Nanoparticles , Humans , Female , Nanomedicine/methods , Nanoparticles/chemistry , Animals , Genital Diseases, Female/drug therapy , Drug Delivery Systems , Leiomyoma/drug therapy , Endometriosis/drug therapy , Polycystic Ovary Syndrome/drug therapy
16.
J Ovarian Res ; 17(1): 100, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734641

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, which often lead to the development of type II diabetes and cardiovascular disease with serious consequences. Current treatment of PCOS with symptomatic treatments such as hormone replacement, which has many side effects. Research on its origin and pathogenesis is urgently needed. Although improving the metabolic status of the body can alleviate reproductive function in some patients, there is still a subset of patients with metabolically normal PCOS that lacks therapeutic tools to address ovarian etiology. METHODS: The effect of IL-22 on PCOS ovarian function was verified in a non-metabolic PCOS mouse model induced by dehydroepiandrosterone (DHEA) and rosiglitazone, as well as granulosa cell -specific STAT3 knockout (Fshrcre+Stat3f/f) mice (10 groups totally and n = 5 per group). Mice were maintained under controlled temperature and lighting conditions with free access to food and water in a specific pathogen-free (SPF) facility. Secondary follicles separated from Fshrcre+Stat3f/f mice were cultured in vitro with DHEA to mimic the hyperandrogenic environment in PCOS ovaries (4 groups and n = 7 per group) and then were treated with IL-22 to investigate the specific role of IL-22 on ovarian function. RESULTS: We developed a non-metabolic mice model with rosiglitazone superimposed on DHEA. This model has normal metabolic function as evidenced by normal glucose tolerance without insulin resistance and PCOS-like ovarian function as evidenced by irregular estrous cycle, polycystic ovarian morphology (PCOM), abnormalities in sex hormone level. Supplementation with IL-22 improved these ovarian functions in non-metabolic PCOS mice. Application of DHEA in an in vitro follicular culture system to simulate PCOS follicular developmental block and ovulation impairment. Follicles from Fshrcre+Stat3f/f did not show improvement in POCS follicle development with the addition of IL-22. In DHEA-induced PCOS mice, selective ablation of STAT3 in granulosa cells significantly reversed the ameliorative effect of IL-22 on ovarian function. CONCLUSION: IL-22 can improve non-metabolic PCOS mice ovarian function. Granulosa cells deficient in STAT3 reverses the role of IL-22 in alleviating ovary dysfunction in non-metabolic PCOS mice.


Subject(s)
Disease Models, Animal , Interleukin-22 , Interleukins , Ovary , Polycystic Ovary Syndrome , Female , Animals , Polycystic Ovary Syndrome/metabolism , Mice , Interleukins/metabolism , Interleukins/genetics , Ovary/metabolism , Ovary/pathology , Dehydroepiandrosterone/pharmacology , STAT3 Transcription Factor/metabolism , Rosiglitazone/pharmacology , Rosiglitazone/therapeutic use , Granulosa Cells/metabolism , Mice, Knockout
17.
J Med Life ; 17(1): 109-115, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38737668

ABSTRACT

Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to compare the effects of green tea tablets and metformin on ovulation, menstrual cycle regularity, and antioxidant biomarkers in women with polycystic ovary syndrome (PCOS). In this clinical trial study, 94 women with PCOS were randomly assigned to three groups: green tea (n = 33), metformin (n = 29), and control (n = 32). Menstrual status and oxidative stress parameters, including total antioxidant capacity, thiol, and lipid peroxidation, were compared before and 3 months after the intervention among all three groups. Data analysis was conducted using SPSS software version 22 and employing the analysis of variance and paired t-tests. Following the intervention, the mean menstrual cycle duration in the green tea, metformin, and control groups was 32.22 ± 12.78, 48.72 ± 37.06, and 48.53 ± 31.04 days, respectively (P = 0.040). There was no statistically significant difference between the three groups in terms of biochemical, hormonal, and antioxidant indices before and after the intervention (P > 0.05). The intake of green tea tablets was associated with better outcomes in regulating the menstrual cycle in women with PCOS.


Subject(s)
Menstrual Cycle , Metformin , Ovulation , Polycystic Ovary Syndrome , Tablets , Tea , Humans , Polycystic Ovary Syndrome/drug therapy , Female , Metformin/therapeutic use , Metformin/pharmacology , Menstrual Cycle/drug effects , Adult , Ovulation/drug effects , Young Adult , Antioxidants/therapeutic use , Oxidative Stress/drug effects
18.
J Ovarian Res ; 17(1): 111, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778429

ABSTRACT

OBJECTIVE: This clinical trial was designed and conducted due to the anti-inflammatory potential of Oleoylethanolamide (OEA) to examine the effect of OEA supplement on glycemic status, oxidative stress, inflammatory factors, and anti-Mullerian hormone (AMH) in women with polycystic ovary syndrome (PCOS). METHOD: This study was a randomized clinical trial, double-blinded, placebo-controlled that was carried out on 90 women with PCOS. Patients were divided into two groups: receiving an OEA supplement (n = 45) or a placebo (n = 45). The intervention group received 125 mg/day OEA and the placebo group received the wheat flour for 8 weeks. Demographic data were collected through questionnaires. Fasting blood sugar (FBS), insulin resistance (IR), total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and AMH were measured before and after the study. RESULTS: Data analysis of food recall and physical activity questionnaires, showed no significant differences between the two groups (p > 0.05). Biochemical factors including glycemic status, MDA, inflammatory factors, and AMH decreased significantly (p < 0.05). TAC increased remarkably (p < 0.05) in comparison between the two groups, after the intervention. CONCLUSION: OEA supplement with anti-inflammatory characteristics could be efficient independent of diet changes and physical activity in improving disrupted biochemical factors, so both supplementation or food resources of this fatty acid could be considered as a compensatory remedy in patients with PCOS. TRIAL REGISTRATION: This study was retrospectively (09-01-2022) registered in the Iranian website ( www.irct.ir ) for registration of clinical trials (IRCT20141025019669N20).


Subject(s)
Anti-Mullerian Hormone , Blood Glucose , Dietary Supplements , Endocannabinoids , Inflammation , Oleic Acids , Oxidative Stress , Polycystic Ovary Syndrome , Humans , Female , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/blood , Oxidative Stress/drug effects , Adult , Oleic Acids/therapeutic use , Oleic Acids/pharmacology , Inflammation/drug therapy , Inflammation/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Anti-Mullerian Hormone/blood , Young Adult , Insulin Resistance , Double-Blind Method , Antioxidants/pharmacology , Antioxidants/therapeutic use
19.
BMC Womens Health ; 24(1): 298, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769509

ABSTRACT

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrine gynecological disease affecting many women of reproductive age. Clomiphene is the first-line treatment for PCOS patients, but most individuals may be resistant to it. This study aims to assess the efficacy of dexamethasone and clomiphene in the treatment of PCOS patients, and to provide a theoretical basis for clinicians to study and treat PCOS. METHODS: Chinese and English databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Medical Network, and VIP Information Chinese Journal Service Platform (VIP) were searched from the inception to January 2023. Review Manager and Stata software were used for meta- analysis. The risk of bias of eligible studies were assessed using Cochrane's risk of bias tool. Publication bias was assessed by funnel plots, Begg's and Egger's tests. RESULTS: A total of 12 literatures were finally included, with a total of 1270 PCOS patients. Compared with the control group, dexamethasone combined with clomiphene could significantly improve pregnancy (RR = 1.71, P < 0.00001), ovulation (RR = 1.30, P < 0.00001), luteinizing hormone level (SMD = -0.94, P < 0.00001), estradiol level (SMD = 0.99, P = 0.05), progesterone level (SMD = 5.08, P = 0.002) and testosterone level (SMD = -1.59, P < 0.00001). However, there were no significant effects on ovulation-stimulating hormone level (SMD = 0.15, P = 0.37), adverse reactions (RR = 1.30, P = 0.30), dizziness (RR = 1.50, P = 0.45), and vomiting (RR = 1.67, P = 0.48). CONCLUSION: The treatment of dexamethasone combined with clomiphene is helpful to improve the ovulation and pregnancy rate in patients with PCOS, and improve the hormone levels of patients.


Subject(s)
Clomiphene , Dexamethasone , Fertility Agents, Female , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/drug therapy , Clomiphene/therapeutic use , Female , Dexamethasone/therapeutic use , Fertility Agents, Female/therapeutic use , Pregnancy , Drug Therapy, Combination , Treatment Outcome , Pregnancy Rate
20.
Endocrinol Diabetes Metab ; 7(3): e490, 2024 May.
Article in English | MEDLINE | ID: mdl-38769719

ABSTRACT

OBJECTIVE: This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. METHODS: This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). RESULT: In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. CONCLUSION: The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.


Subject(s)
Alanine Transaminase , Insulin Resistance , Liver Function Tests , Liver , Polycystic Ovary Syndrome , Triglycerides , Humans , Female , Polycystic Ovary Syndrome/physiopathology , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/complications , Adult , Cross-Sectional Studies , Liver/metabolism , Triglycerides/blood , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Iran/epidemiology , Blood Glucose/metabolism , Young Adult , Cholesterol, HDL/blood , Fatty Liver/etiology , Fatty Liver/physiopathology
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