Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1ß, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

The effect of Myo-Inositol supplement on molecular regulation of folliculogenesis, steroidogenesis, and assisted reproductive technique outcomes in patients with polycystic ovarian syndrome.

RESEARCH QUESTION: The mechanism of Myo-Inositol, as an adjuvant, on key signaling pathways related to oocyte maturation, fertilization rate, and embryo quality as well as ovarian steroidogenesis in cumulus cells of PCOS patients, is still unclear. DESIGN: Infertile patients who were candidates for ART cycles were divided into three groups (n = 30 in each group), including group 1: PCOS patients only receiving folic acid, group 2: PCOS patients receiving daily Myo-Inositol combined with folic acid, and a control group (group 3): normal ovulatory women without PCOS receiving only folic acid from 1 month prior to IVF cycle until the day of ovum pick up. During the ART procedure, oocytes maturation, fertilization rate, and embryo quality were assessed. The gene expressions of FSHR, LHR, CYP11A1, CYP19A1, 3ß-HSD2, and StAR were also analyzed using qRT-PCR. Western blot analysis was performed for the evaluation of AKT, ERK, CREB, and AMPK phosphorylation. RESULT: Despite equal number of retrieved oocytes, the percentages of MII oocytes, fertilization rate, and embryo quality were found to be significantly higher in group 2 due to the administration of inofolic. The expressions of all the studied genes were significantly higher in the cumulus cells of group 1 compared to the group 2. Higher phosphorylation of ERK1/2 was found in the groups 2 and 3 compared to the group 1. On the other hand, p-Akt has significantly decreased in the group 2 compared to the group 1. CONCLUSION: Our study provides new insight into the molecular mechanism underlying the positive effect of Myo-Inositol on intrinsic ovarian defects in PCOS, steroidogenesis, oocyte maturation, fertilization rate, and embryo quality.

The effects of coenzyme Q10 supplementation on metabolic profiles and parameters of mental health in women with polycystic ovary syndrome.

OBJECTIVE: Evaluating the impact of coenzyme Q10 (CoQ10) supplementation on hormonal indices, mental health, and biomarkers of inflammatory responses and oxidative stress among female patients suffering from polycystic ovary syndrome (PCOS). METHODS: The present double-blinded, placebo-controlled randomized clinical trial consisted of 55 PCOS women (aged 18-40 years old), who were randomized into groups receiving 100 mg/day of CoQ10 (28 cases) or placebo (27 cases) for 12 weeks. RESULTS: The supplementation of CoQ10 decreased significantly the scores of Beck Depression Inventory (BDI) (p = .03) and Beck Anxiety Inventory (BAI) (p = .01) and high-sensitivity C-reactive protein (hs-CRP) level (p = .005) when comparing with the placebo group. Moreover, CoQ10 group exhibited a significant drop in total testosterone (p = .004), dehydroepiandrosterone sulfate (DHEAS) (p < .001), hirsutism (p = .002) and malondialdehyde (MDA) (p = .001) levels in the serum, and a significant rise in sex hormone-binding globulin (SHBG) (p < .001) and total antioxidant capacity (TAC) (p < .001) levels in the serum than the placebo group. CONCLUSIONS: 12-week supplementation of CoQ10 to PCOS women showed beneficial impact on BDI, BAI, hs-CRP, total testosterone, DHEAS, hirsutism, SHBG, TAC and MDA levels.

Analysis of Unani coded formulation on the hormonal parameters of patients with polycystic ovarian syndrome.

The effect of Unani coded polyherbal formulations (Picolin) containing: 1) Cinnamomum verum (Bark), 2) Glycyrrhiza glabra (Root), 3) Linum usitatissimum (Seed) and 4) Vitex agnus castus (Seed) on the hormonal levels of polycystic ovarian syndrome (PCOS) patients (n=73) was determined. A randomized controlled multi-center trial was conducted on three groups that received either: 1) Capsule Picolin (n=25, 500 mg, two capsules thrice a day) and 2) Hydroalcoholic extract, tablet Picolin-E (n=23, 250 mg thrice a day) or 3) Metformin (n=25, 500 mg, twice a day) that continued for 12 weeks. The effect of capsule Picolin before and after treatment on serum insulin (14.8±1.8 vs 10.7±1.7µIU/mL) and prolactin (17.7±0.9 vs 8.5±1.1ng/mL) levels were significant. Likewise, the tablet Picolin-E also demonstrated significant effect on serum insulin (16.7±1.7 vs 9.3±0.1µIU/mL) and prolactin (18.5±1 vs 10±1.5ng/mL) levels. On the contrary in metformin treated group these parameters, serum insulin (17.4±1.6 vs 16.4±1.4µIU/mL) and prolactin (21.7±2.8 vs 21±2.8ng/mL) were non-significant. The improvement in the menstrual flow in the PCOS patients after treatment with either capsule Picolin, tablet Picolin-E or metformin were improved by 84%, 61% and 54%, respectively. Unani formulation were comparatively more effective than metformin. The treatment effectiveness was capsule Picolin> tablet Picolin-E>metformin.

A herbal treatment approach for the management of clinical, hormonal and ultrasound parameters in reproductive age group women with polycystic ovarian syndrome: A randomized clinical trial.

Around fifteen percent women of reproductive age have been effected by Polycystic Ovarian Syndrome (PCOS); a complicated disorder; and apparently there is no standard therapy available. Considering this lack, we design present work; for the assessment of a herbal medicine (Femitex-SP4) in managing PCOs. During 2016-17; this study was carried out at Abbasi Shaheed hospital, Karachi, Pakistan. A total of 150 patients aged between 18-44 years were included as per Rotterdam criteria. Patients received 500 mg of powdered herbs in capsule form twice daily. The primary outcomes were regular menstruation and ovulation plus change in fasting blood sugar levels. Changes in free testosterone levels and ovarian morphology was secondary outcome measures. Continuous outcomes before and after treatment were compared by Student's t-test (one tailed, independent). P = 0.05 was considered as significant. Women menstrual cycle was considerably improved. Fasting blood sugar levels did not change (p=0.103392). Progesterone levels were same at the starting point and after treatment (P=0.318322). With complete recovery in 6 patients; a notable change was found in ovarian size. Free testosterone levels were also dropped significantly (p<0.00001). Our main success was drastic improvement in normalizing menstrual cycle during therapy. Herbal treatment is proven to be clinically effective in most of the patients; particularly PCOs patients with menstrual irregularities. Hence, Femitex-SP4 can be taken as a better treatment for PCOs.

Acupuncture regulates the autophagy of ovarian granulosa cells in polycystic ovarian syndrome ovulation disorder by inhibiting the PI3K/AKT/mTOR pathway through LncMEG3.

The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulation dysfunction, which are caused by the excessive autophagy of ovarian granulosa cells. Acupuncture has been shown to improve ovulation dysfunction and abnormal follicular development in PCOS patients, but its mechanism is unclear. This study hypothesized that the beneficial effects of acupuncture are the result of LncMEG3-mediated effects on the PI3K/AKT/mTOR pathway. Acupuncture (CV-4, RN-3, CV-6, SP-6 and EX-CA 1) was used to treat a rat model of polycystic ovary syndrome. Hematoxylin-eosin staining was used to observe ovarian morphology and enzyme-linked immunosorbent assay, western blotting, immunohistochemistry and real-time PCR were used to detect LH, E2, FSH, T, AMH, LncMEG3, PI3K, AKT, mTOR, P62 and LC3II/I expression. The ovarian morphology of 90% of the rats in the acupuncture treatment group was significantly improved after 11 consecutive days of therapy. Acupuncture also resulted in a significant decrease in serum LH, FSH, T and AMH levels and a significant increase in E2 level (P<0.01). LncMEG3, PI3K, AKT, mTOR, P62 and LC3II/I expression was decreased in ovarian granulosa cells after acupuncture compared with PCOS and lentiviral Intervention Group (P<0.05), while the expression of follicle stimulating hormone receptor was increased (P<0.05). These results indicate that acupuncture can down-regulate the expression of LncMEG3 and thereby inhibit the PI3K/AKT/mTOR pathway, reducing granulosa cell autophagy and normalizing their proliferation. These factors ultimately remedy abnormal follicular development. These findings suggest that acupuncture has clinical potential as a safe treatment for PCOS ovulatory dysfunction.

Nutrition Strategy and Life Style in Polycystic Ovary Syndrome-Narrative Review.

Here we present an extensive narrative review of the broadly understood modifications to the lifestyles of women with polycystic ovary syndrome (PCOS). The PubMed database was analyzed, combining PCOS entries with causes, diseases, diet supplementation, lifestyle, physical activity, and use of herbs. The metabolic pathways leading to disturbances in lipid, carbohydrate, and hormonal metabolism in targeted patients are described. The article refers to sleep disorders, changes in mental health parameters, and causes of oxidative stress and inflammation. These conditions consistently lead to the occurrence of severe diseases in patients suffering from diabetes, the fatty degeneration of internal organs, infertility, atherosclerosis, cardiovascular diseases, dysbiosis, and cancer. The modification of lifestyles, diet patterns and proper selection of nutrients, pharmacological and natural supplementation in the form of herbs, and physical activity have been proposed. The progress and consequences of PCOS are largely modifiable and depend on the patient's approach, although we have to take into account also the genetic determinants.

Therapeutic efficacy of biofeedback pelvic floor muscle exercise in women with dysfunctional voiding.

Dysfunctional voiding (DV), a voiding dysfunction due to hyperactivity of the external urethral sphincter or pelvic floor muscles leading involuntary intermittent contractions during voiding, is not uncommon in neurologically normal women with lower urinary tract symptoms (LUTS). We aimed to investigate the therapeutic efficacy of biofeedback pelvic floor muscle training (PFMT) in female patients with DV and to identify the therapeutic efficacy. Thirty-one patients diagnosed with DV. All participates completed the 3-month biofeedback PFMT program, which was conducted by one experienced physiotherapist. At 3 months after treatment, the assessment of treatment outcomes included global response assessment (GRA), and the changes of clinical symptoms, quality of life index, and uroflowmetry parameters. 25 (80.6%) patients had successful outcomes (GRA ≥ 2), and clinical symptoms and quality of life index significantly improved after PFMT. Additionally, uroflowmetry parameters including maximum flow rate, voided volume, voiding efficiency, total bladder capacity, voiding time, and time to maximum flow rate significantly improved after PFMT treatment. Patients with the history of recurrent urinary tract infection in recent 1 year were found to have unsatisfied therapeutic outcomes. In conclusion, biofeedback PFMT is effective in female patients with DV with significant improvements in clinical symptoms, quality of life, and uroflowmetry parameters. The history of urinary tract infection in recent 1 year is a negative predictor of successful outcome.

The relationship between vitamin D3 and insulin in polycystic ovary syndrome - a critical review.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It is characterized by hormonal, reproductive and metabolic disturbances, including hyperandrogenism, altered gonadotropin level, ovarian cysts and ovulatory dysfunction as well as insulin resistance, hyperinsulinemia and dyslipidemia. It was shown that increased insulin concentration is a plausible factor in the pathogenesis of PCOS. Insulin leads to overstimulation of ovarian theca cells to androgen biosynthesis and contributes to insulin resistance in tissues such as muscle, liver, adipose tissue and ovary of PCOS patients. Noteworthy, recent studies suggested that supplementation with vitamin D3 may be an alternative therapy increasing insulin sensitivity and thereby improving reproductive parameters in PCOS women. Indeed, various action of vitamin D3 on the ovarian, hormonal and metabolic features observed in PCOS were presented. Many studies reported therapeutic effects of vitamin D3, but some research found a lack of influence or contradicted these findings. Therefore, the aim of this review was to summarize the available evidence about vitamin D3 and insulin interaction in PCOS, and discusses the potential usefulness of VD3 in PCOS treatment.

Linum usitatissimum seeds oil down-regulates mRNA expression for the steroidogenic acute regulatory protein and Cyp11A1 genes, ameliorating letrezole-induced polycystic ovarian syndrome in a rat model.

The safety and effectiveness of nutricetics suggest that they may offer an alternative to pharmaceutical and surgical therapy for hormone-dependent disorders, such as polycystic ovarian syndrome (PCOS). We investigated the effects of Linum usitatissimum seed oil (LSO) on ovarian functionality, its molecular targets, and the oxidative response in hyperandrogenism-induced polycystic ovary. The composition of LSO has been analyzed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS). A well-established PCOS rat model orally administered with letrozole daily for 21 days was used to investigate the effect of LSO at doses of 1 and 2 mL/kg body weight for 28 days. The effect on hormonal profile and antioxidant status, histopathology (cell proliferation), and the expression ratio of the steroidogenic acute regulatory protein (StAR) and Cyp11A1 gene were evaluated. LSO exerted beneficial effects on PCOS rat models via restoring glutathione (GSH), malondialdehyde (MDA), beta subunit subunit luteinizing hormone (LH), testosterone levels, and histopathological scoring. Furthermore, LSO reversed the elevated StAR and Cyp11A1 genes in the PCOS rat model. This study demonstrated the molecular and cellular mechanisms of the beneficial effect of LSO against the reproductive and metabolic disorders of PCOS.

Caesalpinia bonduc (L.) Roxb. as a promising source of pharmacological compounds to treat Poly Cystic Ovary Syndrome (PCOS): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia bonduc (L.) Roxb. [Family: Fabaceae (Caesalpiniaceae)], known as bonduc nut or fever nut, has been used in India for many years to treat fever, inflammation, diabetes, cardiovascular disorder, cancer and also for birth control. In recent years, the seeds of this plant are consumed to regulate the menstrual disorders in PCOS. Poly cystic ovary syndrome (PCOS) is one of the most common endocrinological disorders faced by women of reproductive-age in several countries. AIM OF THE REVIEW: This review is aimed at providing the updates on the potential of Caesalpinia bonducella in treating the major symptoms of PCOS and also highlights the future research needs. MATERIALS AND METHODS: All the data pertaining to the plant was collected from multiple databases like Google, Science Direct, Springer, PubMed, Reaxys, Sci Finder, Wiley Online library and Taylor and Francis without any language restrictions. Moreover, information related to PCOS treatment was obtained from native medicine practitioners and from Ayurvedic pharmacopeia of India. RESULTS: More than 50 compounds have been identified in the seed kernels of C. bonducella so far. Seed kernel extracts rich in active compounds like bonducellin, caesalpinin, cassane furanoditerpenes, terpernoids, flavonoids and sterols are studied for their anti-diabetic, anti-hyperlipidemic, anti-cancer, anti-pyretic, and anti-oxidant properties. Recent literature has also attributed anti-androgenic and anti-estrogenic potential to this plant which might be helpful in regulating hyperandrogenism, the major predisposing factor contributing to various other clinical symptoms of PCOS. CONCLUSION: Phytochemicals in C. bonducella are effective against several ailments attributed to PCOS. However, there are no experiments done in PCOS animal models to claim the direct application of C. bonducella in PCOS treatment. Hence, further dose dependent toxicity studies are warranted in animal PCOS models and in PCOS patients to support the traditional evidence of the plants' potential to treat PCOS.

Effect of Vitamin D Status on Vascular Function of the Aorta in a Rat Model of PCOS.

Polycystic ovary syndrome (PCOS) is associated with elevated cardiovascular risk. Early vascular dysfunction may lead to the development of cardiovascular disease in PCOS. Vitamin D deficiency (VDD) is a common comorbidity of PCOS that contributes to the pathogenesis of the disease and its complications. Both PCOS and VDD are accompanied by increased oxidative stress that may be involved in the arising vascular dysfunction. We aimed to investigate the role of vitamin D status on aortic function. PCOS was induced by an 8-week-long transdermal testosterone treatment of female rats, and low and adequate vitamin D status was achieved by dietary means. Contraction and relaxation abilities of isolated aortic segments were measured by myograph. Resorcin-fuchsin staining and immunohistochemical labeling of 3-nitrotyrosine were performed. No difference was shown in the norepinephrine-induced contraction of the aortas of different groups, whereas we detected reduced acetylcholine- and insulin-evoked relaxation in VDD groups. A lower level of resorcin-fuchsin staining and elevated 3-nitrotyrosine immunostaining was observed in VDD. In our study, we demonstrated early endothelial dysfunction in VDD PCOS rat model. Vitamin D supplementation could prevent vascular disturbances, while VDD itself damaged endothelium-dependent vasorelaxation and induced nitrative stress.

Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial.

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect -0.335, 95% CI -0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

Hypothalamic Inflammation as a Potential Pathophysiologic Basis for the Heterogeneity of Clinical, Hormonal, and Metabolic Presentation in PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. It is a heterogeneous condition characterized by reproductive, endocrine, metabolic, and psychiatric abnormalities. More than one pathogenic mechanism is involved in its development. On the other hand, the hypothalamus plays a crucial role in many important functions of the body, including weight balance, food intake, and reproduction. A high-fat diet with a large amount of long-chain saturated fatty acids can induce inflammation in the hypothalamus. Hypothalamic neurons can sense extracellular glucose concentrations and participate, with a feedback mechanism, in the regulation of whole-body glucose homeostasis. When consumed nutrients are rich in fat and sugar, and these regulatory mechanisms can trigger inflammatory pathways resulting in hypothalamic inflammation. The latter has been correlated with metabolic diseases, obesity, and depression. In this review, we explore whether the pattern and the expansion of hypothalamic inflammation, as a result of a high-fat and -sugar diet, may contribute to the heterogeneity of the clinical, hormonal, and metabolic presentation in PCOS via pathophysiologic mechanisms affecting specific areas of the hypothalamus. These mechanisms could be potential targets for the development of effective therapies for the treatment of PCOS.

Effect of electroacupuncture on the kisspeptin system in a pubertal rat model of polycystic ovary syndrome.

OBJECTIVE: To explore the effects and mechanism of action of electroacupuncture (EA) in a rat model of pubertal polycystic ovary syndrome (PCOS). METHODS: Female offspring of Sprague-Dawley rats receiving dihydrotestosterone (DHT) during pregnancy (days 16-19), as a model of prenatal androgenization, were divided randomly into three groups: model group (M), EA group, and sham acupuncture (SA) group (n = 8 each). A normal (N) group comprising female offspring of healthy pregnant rats not receiving DHT (n = 8) was added. EA was administered at CV6 and bilateral SP6/ST36 with 2 Hz frequency and 2 mA intensity. SA consisted of superficial needling at different locations without electrical stimulation. RESULTS: EA improved the disturbed estrous cycles, while it could not be concluded that SA was effective in this respect. EA improved ovarian morphology including the number of corpora lutea and area of the ovary, whereas SA did not. However, both EA and SA attenuated the increased luteinizing hormone and decreased estradiol and gonadotropin-releasing hormone levels in the serum of PCOS model rats. Levels of testosterone, follicle-stimulating hormone, and progesterone did not significantly differ between groups. EA and SA alleviated the upregulation of kisspeptin protein and mRNA levels in the hypothalamus and kisspeptin protein level in the arcuate nucleus (ARC). No differences were found between groups in protein or mRNA expression of dynorphin (DYN) or neurokinin B (NKB) in the hypothalamus. Co-expression of kisspeptin, NKB, and DYN were observed in ARC. The GnRH level in the median eminence decreased and could be rescued by EA and SA. Intriguingly, kisspeptin levels in the granulosa cells of the ovary decreased in the model group and could be rescued by EA but not SA. Levels of kisspeptin, NKB, and DYN protein and mRNA in the ovary did not differ between any groups. CONCLUSION: Both EA and SA appeared to improve symptoms of PCOS at puberty by modulating the kisspeptin system in the hypothalamus. EA also had an effect on ovarian kisspeptin expression and a more comprehensive effect with respect to improving PCOS at puberty than SA.

Influence of n-3 fatty acid supplementation on inflammatory and oxidative stress markers in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is defined as a reproductive endocrine disease that results in a low-grade inflammatory and pro-oxidant state. Dietary factors, including n-3 fatty acids, may have a key role in improving metabolic disorders in PCOS patients. The present study aimed to investigate the influence of n-3 fatty acid supplementation on inflammatory and oxidative stress (OS) markers in patients with PCOS. A systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus and Lilacs, until November 2019, was conducted. Randomised clinical trials that reported inflammatory and OS markers as endpoints in women with PCOS receiving n-3 fatty acid supplementation were included. The pooled estimates of the weighted mean differences (WMD) and the standard mean differences (SMD) were calculated. Random effects models were adopted to measure the pooled outcomes. Among the 323 studies retrieved, ten fulfilled the inclusion criteria for a meta-analysis. We founded a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (SMD -0·29 (95 % CI -0·56, -0·02) mg/l) and an increase in adiponectin (WMD 1·42 (95 % CI 1·09, 1·76) ng/ml) concentrations in the intervention group when compared with the placebo group. No statistically significant results were found in the meta-analysis for visfatin, nitric oxide, GSH or malondialdehyde levels or total antioxidant capacity. The data suggest that supplementation of n-3 fatty acids could reduce the inflammatory state in women with PCOS, through a decrease in hs-CRP and an increase in adiponectin levels.

Salicylate administration suppresses the inflammatory response to nutrients and improves ovarian function in polycystic ovary syndrome.

Oxidative stress (OS) and inflammation are often present in polycystic ovary syndrome (PCOS). We examined the effects of salsalate treatment on nutrient-induced OS and inflammation, ovarian androgen secretion, ovulation, and insulin sensitivity in PCOS. Eight lean insulin-sensitive women with PCOS and eight age- and body composition-matched ovulatory controls for baseline comparison participated in the study. The women with PCOS underwent a 12-wk treatment of salsalate, a nonsteroidal anti-inflammatory drug, at a dose of 3 g daily. Markers of OS and inflammation were quantified in mononuclear cells (MNC) and plasma from blood drawn fasting and 2 h after saturated fat ingestion before and after treatment. Ovarian androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration before and after treatment. Ovulation was documented based on biphasic basal body temperatures and luteal range progesterone elevations. A two-step pancreatic clamp was performed pre- and posttreatment to measure basal endogenous glucose production (EGP) and the steady-state glucose disposal rate (GDR) during the euglycemic phase and markers of OS and inflammation in MNC and plasma during the hyperglycemic phase. Salsalate administration suppressed lipid- and glucose-stimulated reactive oxygen species generation, activated nuclear factor-κB and circulating tumor necrosis factor-α, normalized basal androgen levels, and lowered HCG-stimulated androgen secretion without altering EGP or GDR. Four salsalate-treated subjects responded with two consecutive ovulations. We conclude that in PCOS, salsalate-induced suppression of OS and inflammation ameliorates ovarian androgen hypersecretion and may induce ovulation while maintaining insulin action.

Effectiveness of acupuncture in polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of acupuncture in reproductive-age females with polycystic ovary syndrome (PCOS). METHODS: We searched the Pubmed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chongqing VIP databases for the relevant literature. The meta-analysis was performed with a random-effects model with RevMan 5.3. The primary outcomes of interest included the rate of live birth, pregnancy and ovulation, and the secondary outcomes included the recovery of menstrual period and hormone levels. Results were expressed as the relative risk (RR) for the discrete data and the mean difference (MD) for the continuous outcomes with a 95% confidence interval (CI). RESULTS: Twenty two studies with 2315 participants were included in this systematic review and meta-analysis. A pooled analysis showed a recovery of the menstrual period (5 trials; 364 participants; SMD, -0.52; 95% CI [-0.89, -0.14]; I = 67%; P = .0007; low certainty) in the acupuncture group. Furthermore, there were significant decreases in the luteinizing hormone (LH) (13 trials; 917 participants; MD, -0.92; 95% CI [-1.43, -0.41]; I = 60%; P = .0004; very low certainty) and testosterone (13 trials; 923 participants; SMD, -0.46; 95% CI [-0.73, -0.20]; I = 75%; P = .0006; very low certainty) in the acupuncture group. No significant differences were observed in the rates of live birth, pregnancy, and ovulation, and no significant differences were observed in the LH/follicle-stimulating hormone (FSH) ratio. CONCLUSIONS: There was insufficient evidence to support that acupuncture could promote live birth, pregnancy, and ovulation. However, acupuncture could promote the recovery of menstrual cycles as well as downregulate the levels of LH and testosterone in patients with PCOS. STUDY REGISTRATION: PROSPERO CRD42019128574.

The phytoestrogen, quercetin, in serum, uterus and ovary as a potential treatment for dehydroepiandrosterone-induced polycystic ovary syndrome in the rat.

The exact mechanisms of polycystic ovary syndrome (PCOS) are unknown and there is no effective cure for the disease. The aim of this study was to evaluate the alterations in serum oestradiol and adiponectin levels and in the expression of some important genes in the uterine and ovarian tissues of PCOS rats. The therapeutic effect of quercetin on PCOS was also assessed. Rats were divided into five groups: control, ethanol, quercetin (Q), PCOS and PCOS+Q. After 30 days of oral treatments, the rats' ovaries and uteri were removed and nesfatin-1, aromatase and adipoR1 expressions were quantified with real-time polymerase chain reaction. Serum adiponectin and oestradiol levels were evaluated using enzyme-linked immunosorbent assay technique. The results of this study showed that expression of nesfatin-1 and adipoR1 genes and adiponectin serum levels decreased in the PCOS rats, but aromatase expression and oestradiol level increased. Treatment with quercetin increased the adiponectin level and expression of adipoR1 and nesfatin-1 and decreased both the expression of aromatase and the oestradiol level. Quercetin improved PCOS by phytoestrogenic effects and mimicking oestrogen's function. Quercetin also affects important factors in both the uterus and ovary and could improve the obesity and the diabetic and infertility symptoms of PCOS.

The relationship between Vitamin D deficiency and polycystic ovary syndrome.

BACKGROUND: Vitamin D deficiency is frequently seen in patients with polycystic ovary syndrome (PCOS) and has been shown to exhibit multiple effects on the disease process. The purpose of this study was to investigate the role of vitamin D deficiency in complex PCOS pathophysiological pathways. METHODS: Two hundred sixty-seven patients with PCOS were divided into two groups Group 1 with 25(OH)D3 deficiency, and Group 2 with normal 25(OH)D3. Biochemical and hormonal parameters (androgen hormones, gonadotropins, and thyroid function tests) were compared between the two groups. RESULTS: Eighty-six percent of the patients (n=231) were in Group 1 and 14% (n=36) in Group 2. Statistically significantly higher concentrations of serum testosterone, dehydroepiandrosterone-sulfate and LH were determined in Group 1 (p<0.05). 25(OH)D3 concentrations were negatively correlated with body mass index (r=-0.459), serum testosterone (r =-0.374) and dehydroepiandrosterone-sulfate levels (r=-0.418); (all; p< 0.05). CONCLUSION: The study findings show that low 25(OH)D3 levels are associated with high androgen levels in women with PCOS. Vitamin D deficiency should be considered as an additional risk factor in the development of PCOS. We think that providing vitamin D supplementation for women from identified deficiency areas can reduce the risk of PCOS development.