Treatment Of Polycystic Ovary Syndrome Research Articles

Bridging gap in treatment of polycystic ovarian syndrome through drug repurposing: what we achieved and where we are?

Polycystic ovarian syndrome (PCOS) is one of the chief causes of infertility in women of reproductive age. Several drugs belonging to the oral contraceptive class have been approved for the treatment of PCOS. Nonetheless, the capability to target only a few symptoms of PCOS and fatal side effects are key hurdles to their use. Therefore, repurposing existing drugs can be promising in managing PCOS efficiently. Drugs from different pharmacological classes like antidiabetics (metformin, rosiglitazone, pioglitazone, and semaglutide), statins (simvastatin and atorvastatin), antiandrogen drugs (finasteride and flutamide), etc. demonstrated significant potential in managing PCOS. The present review offers a comprehensive overview of all the medications examined as potential repurposed options for the efficient treatment of PCOS. The pathogenesis of PCOS, existing therapies for PCOS and their challenges, drug repurposing and its significance is also explained. The small-molecular drugs from various pharmacological classes and different phytoceuticals repurposed against PCOS are discussed along with their anti-PCOS activity mechanisms. Moreover, novel drug targets responsible for PCOS and opportunities for drug repurposing are briefed. The repurposed drugs in clinical trials for PCOS and drug repurposing challenges are discussed. Thus, drug repurposing can serve as a potential way to effectively treat PCOS, reducing the extent of infertility and improving the quality of life of women.

Effect of Rhei Radix Et Rhizome on treatment of polycystic ovary syndrome by regulating PI3K/AKT pathway and targeting EGFR/ALB in rats

Ethnopharmacological relevanceAbnormal endocrine metabolism caused by polycystic ovary syndrome (PCOS) poses a serious risk to reproductive health in females. According to Traditional Chinese Medicine (TCM) theories, the leading causes of PCOS include turbid phlegm, blood stasis and stagnation of liver Qi. Rhei Radix Et Rhizome is widely used in TCM to attack stagnation, clear damp heat, relieve fire. Rhei Radix Et Rhizome is an important part of the TCM formulas for the treatment of PCOS, which has a long history of medicinal use. However, the specific effect and mechanisms of Rhei Radix Et Rhizome on PCOS have yet to be elucidated. Aim of the studyThe object of this study aimed to investigate the effect and its pharmacological mechanism of Rhei Radix Et Rhizome on the treatment of polycystic ovary syndrome. MethodsPCOS was induced in female Sprague Dawley (SD) rats by administering letrozole (1 mg/kg, per orally, p.o.) for 21 days, then treated with Rhei Radix Et Rhizome at doses of 0.6g/kg or 1.2g/kg. Rats weight, blood glucose and estrus period are measured, and serum hormone include free testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and ovarian lesions were observed to determine the effects of Rhei Radix Et Rhizome. Network pharmacology and molecular docking predicted the targets of Rhei Radix Et Rhizome on PCOS. Epidermal growth factor receptor (EGFR), albumin (ALB), PI3K and P-AKT/AKT protein expression levels in ovarian tissues were assessed by Western blot. ResultsRhei Radix Et Rhizome reduce abnormal weight and fasting blood glucose induced by letrozole (n=5, p < 0.01), and improve the disturbed estrus cycle, reduce T, LH levels and LH/FSH ratio of PCOS rats (n=4, p < 0.01). In addition, it alleviates the polycystic changes of ovaries in PCOS rats and reduces ovarian histopathological damage (n=4, p < 0.01). Additionally, the core active components of Rhei Radix Et Rhizome for PCOS include Sennoside D_qt, Procyanidin B-5,3'-O-gallate, and Mutatochrome, which strongly bind to core therapeutic targets ALB and EGFR. Furthermore, the treatment reduces the increase of EGFR and ALB induced by letrozole (n=4, p < 0.01). KEGG pathway enrichment analysis highlights endocrine resistance and prolactin signaling pathway, in both of which the PI3K/AKT pathway plays a crucial role. Our results show Rhei Radix Et Rhizome rescue the abnormal expression of PI3K/AKT pathway in PCOS rats (n=4, p < 0.01). However, no significant dose-dependent relationship was observed in the tested dose range for the above experiments. ConclusionThese findings suggest that Rhei Radix Et Rhizome can regulate the PI3K/AKT pathway and target EGFR and ALB to treat polycystic ovary syndrome in rats. This study provides a scientific basis for the use of Rhei Radix Et Rhizome in the treatment of PCOS and highlights its potential mechanism through modulation of the PI3K/AKT pathway.

Nampt/SIRT2/LDHA pathway-mediated lactate production regulates follicular dysplasia in polycystic ovary syndrome

Decreased nicotinamide adenine dinucleotide (NAD+) content has been shown to contribute to metabolic dysfunction during aging, including polycystic ovary syndrome (PCOS). However, the effect of NAD+ on ovulatory dysfunction in PCOS by regulating glycolysis has not been reported. Based on the observations of granulosa cells (GCs) transcriptome data from the Gene Expression Omnibus (GEO) database, the signal pathways including glycolysis and nicotinate-nicotinamide metabolism were significantly enriched, and most genes of the above pathway like LDHA and SIRT2 were down-regulated in PCOS patients. Therefore, the PCOS rat model was established by combining letrozole with a high-fat diet (HFD), we demonstrate that in vivo supplementation of nicotinamide mononucleotide (NMN) significantly improves the ovulatory dysfunction by facilitating the follicular development, promoting luteal formation, as well the fertility in PCOS rats. Furthermore, target energy metabolomics and transcriptome results showed that NMN supplementation ameliorates the lactate production by activating glycolytic process in the ovary. In vitro, when NAD+ synthesis and SIRT2 expression were inhibited, lactate content in KGN cells was decreased and LDHA expression was significantly inhibited. We confirmed that FK866 can enhance the acetylation of LDHA on 293T cells by Co-immunoprecipitation (Co-IP) assay. We also observed that inhibition of NAD+ synthesis can reduce the activity and increase the apoptosis of KGN cells. Overall, these benefits of NMN were elucidated and the Nampt/SIRT2/LDHA pathway mediated lactate production in granulosa cells played an important role in the improvement of follicular development disorders in PCOS. This study will provide experimental evidence for the clinical application of NMN in the treatment of PCOS in the future.

Progress in TLR4/NF-κB Pathway Regulation by Traditional Chinese Medicine for the Treatment of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women, affecting women's fertility and cardiovascular system. Due to the complexity of its pathogenesis, there are many adverse reactions commonly used in clinical treatment, and the therapeutic effect is short-lived and temporary. TLR4/NF-κB pathway is a classical signaling pathway related to inflammation, and the effective components of TCM compounds and TCM monomers have been proven to reduce the levels of various inflammatory factors in patients by regulating the TLR4/NF-κB pathway, so as to achieve the effect of PCOS. The potential value of TCM in prevention and treatment of PCOS based on TLR4/NF-κB pathway was revealed. This article aims to summarize the recent studies on the improvement of PCOS symptoms by regulating the expression of TLR4/NF-κB pathway by Chinese medicine, so as to further study the mechanism of PCOS prevention and treatment by this pathway under the regulation of Chinese medicine, so as to open up new ideas for the development of new drugs targeting this pathway and clinical research.

Relationship between smoking, excessive androgen and negative emotions in women with polycystic ovary syndrome (PCOS)

BackgroundLifestyle intervention is the first-line treatment for PCOS. Numerous studies have investigated the effect of various lifestyle factors, including dietary habit, smoking, and alcohol consumption on PCOS women. These studies have found that such factors may be associated with physiological parameters such as androgen, and emotional states like anxiety or depression. Smoking, a harmful lifestyle habit widely recognized to contribute to various diseases, has also been found to be related to PCOS. Current research has not adequately compared the effects of smoking with other lifestyle habits on PCOS, and there is little mention of its relationship with the emotional states of patients with PCOS. To further elucidate the association between smoking and other lifestyle factors with clinical symptoms in patients with PCOS, we conducted a cross-sectional evaluation using data from Peking University Third Hospital, with a special focus on analyzing smoking habits and comparing it with a variety of lifestyle factors.MethodsThis cross-sectional study included 601 PCOS women and 184 healthy controls who underwent physical examinations, hormone profiles and psychological measures. We assessed the association between smoking and the clinical symptoms in PCOS women.ResultsWe found a significant correlation between smoking and the degree of depression in PCOS women among the three emotional states: anxiety, depression, and stress. Smoking was also significantly associated with testosterone level in PCOS participants, suggesting that PCOS women who smoke exhibited more severe depressive symptoms and higher testosterone level. In addition, compared to the control group, PCOS women had notably higher testosterone (T) and luteinizing hormone (LH) levels. Smoke and alcohol were statistically significantly more common in women with PCOS than the Control.ConclusionWomen with PCOS who smoke were found to have elevated testosterone levels and more severe depression. These findings suggest that clinicians should monitor smoking women with PCOS for symptoms of depression and assess their hyperandrogenic status.

ER stress-induced LINC00173 promotes the apoptosis of ovarian granulosa cells by regulating the HRK/PI3K/AKT pathway in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and metabolic abnormality disease that mainly affects women of reproductive age. LINC00173, a novel long noncoding RNA (lncRNA), has emerged as an important factor in the development of PCOS. However, the role of LINC00173 in PCOS development and its specific upstream and downstream mechanisms remain to be further clarified. Here, we found that LINC00173 was significantly upregulated in granulosa cells (GCs) of PCOS patients, and played a crucial role in promoting apoptosis of GCs. Mechanistically, we observed the activation of endoplasmic reticulum (ER) stress in the GCs of PCOS patients, and the ER stress sensor ATF4 could directly induce LINC00173 expression by binding to its promoter. LINC00173 further upregulated the expression of Harakiri (HRK) and subsequently inhibited downstream PI3K/AKT pathway. In conclusions, our study uncovered that ER stress-induced upregulation of LINC00173 leads to increased HRK expression and inhibition of the PI3K/AKT pathway, thereby promoting the progression of PCOS. These findings provide a new therapeutic strategy for the treatment of PCOS.

Application of Fluorescent Composite Materials as a Sustained Release System in Treatment of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease characterized by oxidative stress and follicular dysfunction, leading to menstrual irregularities, hyperandrogenism, and infertility. Traditional drug delivery methods often result in drug loss and side effects on normal tissues. To address these issues, we synthesized two novel Co(II)-containing coordination polymers (CPs), {[Co(L)(H2O)2]·2H2O}n (1) and {[Co(L)(H2O)2]·1.5H2O}n (2), through the reaction of the T-shaped ligand (4 - 3'-pyridyl-,6 - 4'-carboxylphenyl)picolinic acid (H2L) with Co(NO3)2·6H2O via a solvothermal process. Fluorescence spectroscopy revealed that the fluorescence emission of the CPs originates from the ligand, indicating their potential application as blue fluorescence materials. Subsequently, we encapsulated these CPs with hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) hydrogels to create two types of metal gel particles carrying spironolactone (HA/CMCS-CPs@spironolactone). SEM and TEM analyses showed that the material consists of tightly stacked sheet-like structures with an average size of approximately 100nm. Thermogravimetric analysis (TGA) indicated that the material begins to decompose at around 115°C, demonstrating good thermal stability. We assessed the inhibitory effects of these materials on oxidative stress induced by PCOS. The results showed that both types of spironolactone-loaded metal gel particles significantly reduced malondialdehyde (MDA) levels, particularly the particles constructed with CP2. HA/CMCS-CP1@spironolactone reduced MDA levels by approximately 17% and 46% at low and high concentrations, respectively, while HA/CMCS-CP2@spironolactone decreased MDA levels by about 55% and 39% at high and low concentrations, respectively. Therefore, the novel drug delivery system reported in this study has the potential to become a safe and effective option for the localized treatment of PCOS.

Beneficial Effects of Curcumin in Polycystic Ovary Syndrome: A Review of Recent Literature and Underlying Mechanisms.

Polycystic Ovary Syndrome (PCOS) is a common endocrinological disorder that affects women of reproductive age and can lead to infertility. The prevalence of PCOS ranges from 5-21% depending on the diagnostic criteria and study population. Clinical manifestations include irregular or absent menstrual periods, obesity, and signs of hyperandrogenism. PCOS can also lead to long-term consequences such as metabolic syndrome, increased risk of cardiovascular diseases, endometrial cancer, diabetes mellitus, and hypertension. Metformin and oral contraceptive pills are the most commonly used drugs for PCOS management, but their efficiency is limited and they have some considerable side effects. Researchers are looking into alternative therapeutic options such as phytochemicals. Curcumin (CUR) is a polyphenolic compound found in the rhizome of Curcuma longa and has shown promising effects for females with PCOS. CUR exerts its anti-PCOS effects through different mechanisms such as reducing oxidative stress and inflammation, balancing hormone levels, and controlling the blood sugar and lipid profile. It can also reduce insulin resistance, regulate menstruation, and improve ovarian morphology and function. Despite its beneficial effects, CUR faces several challenges and limitations in clinical use, such as low bioavailability, instability, and rapid elimination. Therefore, researchers are investigating the potential of CUR nanoformulations and new drug delivery systems to overcome these barriers. With growing evidence regarding the potential role of CUR in PCOS treatment, we decided to provide an updated summary of the recent literature from clinical and preclinical studies on this topic.

Multiple Benefits of Empagliflozin in PCOS: Evidence from a Preclinical Rat Model.

Polycystic ovary syndrome (PCOS) is the most common complex endocrinological condition of women that is associated with infertility and metabolic disorders during the reproductive period. Recently, a great deal of research has focused on the etiopathogenesis of this disorder and the modulation of therapeutic approaches. There are still many controversies in the choice of therapy, and metformin is one of the most commonly used agents in the treatment of PCOS. Considering the link between metabolic disorders and PCOS, glycemic status is crucial in these patients, and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) represent a potentially promising new therapeutic approach. These drugs have been shown to improve glucose metabolism, reduce adipose tissue, decrease oxidative stress, and protect the cardiovascular system. These data prompted us to investigate the effects of empagliflozin (EMPA) in a PCOS rat model and compare them with the effects of metformin. We confirmed that EMPA positively affects somatometric parameters, glucose and lipid metabolism, and the levels of sex hormones, as well as reduces oxidative stress and improves ovarian function and morphology. Administration of EMPA at doses of 5 mg/kg, 15 mg/kg, and 45 mg/kg during a 4-week treatment period improved, as induced by estradiol valerate and a high-fat diet, the metabolic and reproductive statuses in a PCOS rat model. The best effects, which were comparable to the effects of metformin, were achieved in groups receiving the middle and highest applied doses of EMPA. These results may prompt further clinical research on the use of EMPA in patients with PCOS.

7941 Comparison of Metformin with Inositol versus Metformin Alone in Women with Polycystic Ovarian Syndrome (PCOS): A Systematic Review and Meta Analysis of Randomized Controlled Trials

Abstract Disclosure: F.A. Kelly: None. A.D. Lôbo: None. I.B. Andrade: None. P.G. Lima: None. I.P. da Silva: None. M.C. Souza: None. V. Morbach: None. M.S. Barros: None. F.A. Moraes: None. M.B. Jardine: None. L.M. Lopes: None. M.P. Lima: None. M.G. Leite: None. R.Y. Ura Sudo: None. J.C. Cardoso: None. A.M. De Almeida: None. F.D. Pessôa: None. Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. It addresses the chronic inflammatory state of PCOS and improves ovulation, metabolic parameters, and fertility.In recent years, inositols, specifically myo-inositol, and D-chiro-inositol, have emerged as potential treatment options for PCOS. These compounds act as a messenger for hormones, including insulin and follicle-stimulating hormones. Inositols effectively address insulin resistance and modulate the insulin signaling pathways.Although inositols have recently been included in the recommendations of the European Journal of Endocrinology's 2023 International evidence-based guideline for improvement in metabolic measures and considered with benefits in ovulation, hirsutism, and weight in patients with PCOS, the confidence in the available evidence supporting their use is considered to be limited. We aimed to perform a meta-analysis to understand the role of inositol, on glycemic control, LH/FSH ratio, hirsutism, HOMA-IR, and body mass index (BMI) in individuals with polycystic ovary syndrome (PCOS).PubMed, Embase, and Cochrane databases were systematically searched for RCTs comparing the use of metformin alone versus metformin and inositol in patients with polycystic ovary syndrome. Statistical analysis was performed in R software 4.3.1. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of &amp;lt; 0.05 was considered statistically significant. Heterogeneity was examined with the Cochran Q test, prediction interval, and I² statistics. A total of 4 RCTs and 277 patients were included, of whom 138 were randomized to metformin alone and 139 to metformin plus myo-inositol. Compared with metformin alone, Myo-inositol plus Metformin significantly reduced hirsutism (MD -0.97; 95% CI -1.53; -0.40; p=0.0008) and LH/FSH ratio (MD -0.15; 95% CI -0.26, -0.03; p=0.02). There was no significant difference between groups for BMI (MD: 0.97; 95% CI -0.37, 2.32; p=0.16) and HOMA-IR (MD -0.17; 95% CI -0.35, 0.01; p=0.07).In this meta-analysis of RCTs of patients with polycystic ovary syndrome, inositol was associated with a reduction in hirsutism and LH/FSH ratio, compared with metformin monotherapy. Further studies are needed to clarify whether there are benefits for the use of inositol in PCOS treatment. Presentation: 6/3/2024

8699 ​​Efficacy of Glucagon-like Peptide-1 Analogs In Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract Disclosure: F.A. Kelly: None. A.D. Lôbo: None. I.P. da Silva: None. J.C. Cardoso: None. M.S. Barros: None. F.D. Pessôa: None. M.G. Leite: None. R.Y. Ura Sudo: None. A.M. De Almeida: None. F.A. Moraes: None. V. Morbach: None. M.C. Souza: None. P.G. Lima: None. M.P. Lima: None. I.B. Andrade: None. M.B. Jardine: None. L.M. Lopes: None. Polycystic ovary syndrome (PCOS) affects one in ten women of reproductive age, painting a complex picture of metabolic dysfunction. Its hallmark triad includes irregular menstrual cycles, androgen excess, and polycystic ovaries. Beyond infertility concerns, PCOS carries a heavy burden of metabolic imbalances, often characterized by insulin resistance, dyslipidemia, and chronic low-grade inflammation. These intertwined factors place women with PCOS at increased risk for type 2 diabetes and cardiovascular disease, posing a significant long-term health challenge. Current first-line treatments like metformin focus mainly on managing insulin resistance and regulating menstrual cycles. However, unmet needs remain in addressing the broader metabolic derangements and preventing associated health complications. In light of this, glucagon-like peptide-1 (GLP-1) analogs have emerged as potential game-changers in the PCOS treatment landscape. Their multifaceted effects on metabolism beyond blood sugar regulation offer a promising avenue for optimizing care and improving long-term health outcomes in women with PCOS. This meta-analysis aims to evaluate the use of GLP-1 analogs on patients with PCOS to reduce body mass index (BMI), glycated hemoglobin (HbA1C), fasting blood glucose (FBG), high density lipid (HDL), low density lipid (LDL) and triglyceride. PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCT) comparing the use of GLP-1 analogs to placebo or other therapies in patients with PCOS. Treatment effects for continuous endpoints were pooled through mean differences (MD) with 95% confidence intervals. Heterogeneity was evaluated with the Cochran Q test, the prediction interval and I² statistics. Statistical analysis was performed in Revman 5.4. The results were reported following the Preferred Reporting Items for Systematic Review (PRISMA) guidelines.A total of 4 RCTs with 228 patients were included, of whom 137 were randomized to GLP-1 therapy, 58 to placebo, and 33 to other treatments. Over a mean follow-up time of 24 weeks, patients submitted to GLP-1 analogs presented significant decreases in HbA1C (MD -1.40%; 95% CI -1.64 to -1.16; p&amp;lt;000001; I²=0% ), FBG (MD -4.40 mg/dL; 95% CI -7.63 to -1.17; p=0.008; I²=0%) and HDL-c (MD -0.82 mg/dL; 95% CI -1.33 to -0.31; p=0.002; I²=3%); and a nonsignificant increase in LDL-c (MD 0.37 mg/dL; 95% CI -1.30 to 2.03; p=0.67; I²=0%); and nonsignificant decrease in BMI (MD -1.28 Kg/m²; 95% CI -3.18 to 0.63; p=0.19; I²=98%), and triglyceride (MD -10.50 mg/dL; 95% CI -22.81 to 1.81; p=0.09; I²=0%).In this meta-analysis of RCTs of patients with PCOS, the use of GLP-1 analogs showed a significant reduction in HbA1C, FBG, and HDL-c. A larger sample size of people are needed for further statistical analyses. Presentation: 6/3/2024

Short-Term Metformin Therapy in Clomiphene Citrate Resistant PCOS Patients Improves Fertility Outcome by Regulating Follicular Fluid Redox Balance: A Case-Controlled Study.

To determine the effect of short-term metformin administration on follicular fluid (FF) total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and nuclear factor kappa B (NF-kB) in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Fifty-eight patients aged 23-34 who were planned to have intracytoplasmic sperm injection due to clomiphene citrate-resistant PCOS were included in the study. Participants were divided into two groups according to whether they used metformin or not. While 30 of 58 PCOS patients were using short-term metformin in combination with controlled ovarian stimulation, 28 PCOS patients were not using metformin. Metformin was started in the mid-luteal period and continued until the day before oocyte retrieval at 850 mg twice daily. To determine FF-NF-kB, TAS, TOS and OSI values, a dominant follicle ≥17-18 mm in diameter was selected for aspiration. The number of mature follicles and fertilization rates of the metformin group were significantly higher than those not taking metformin. FF-TOS and OSI of the metformin group were significantly lower than those of the group not receiving metformin. Patients receiving metformin had higher FF-TAS than the group not receiving metformin. FF-NF-kB levels of the metformin group were significantly lower than the group not receiving metformin. Insulin resistance, FF-NF-kB and FF-TOS were negatively correlated with the number of mature oocytes. FF-TAS was positively correlated with the number of oocytes. Short-term metformin treatment in clomiphene-resistant PCOS improves the number of mature follicles and fertilization rates by regulating the intra-follicle redox balance.

Diagnosis and treatment of polycystic ovarian syndrome: an update

Polycystic ovarian syndrome (PCOS) and polycystic ovarian disease (PCOD) affect women’s reproductive health. Specifically, PCOS involves elevated androgens, leading to abnormal oocyte growth, ovulation, and ovary fluid accumulation. Likewise, PCOD entails hormonal imbalances that lead to the formation of follicular cysts and the retention of immature eggs. Such symptoms include menstrual irregularities, obesity, hirsutism, depression, infertility, and excessive facial hair growth. The illnesses affect over 116 million women globally. Although the exact reasons are unknown for certain, elevated ratios or LH/FSH and GnRH rates could contribute to this. Treatment strategies include medication, surgery, changes in lifestyle, and exploration of alternative therapies for getting hormone levels under control and handling symptoms. Diagnosis is made by using a medical history, physical examination, blood tests, and ultrasound. They are advised to maintain a healthy diet and minimize exposure to unhealthy meals.

Available Treatments and Adjunctive Therapies for Polycystic Ovarian Syndrome (PCOS) Patients of Reproductive Age: A Scoping Review.

Polycystic ovarian syndrome (PCOS) impacts the health of women worldwide. It is a condition consisting of dysfunctional cystic ovaries resulting in hormonal imbalance. Many women have symptoms such as infertility, increased production of androgens, and insulin resistance. Barriers to effective treatment of PCOS include issues such as delays in diagnosis and inconsistencies in treatment plans among physicians. Despite the current use of available medications to decrease symptomatology, women with PCOS continue to report a decreased quality of life. Using the electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ScienceDirect, a scoping review was conducted on the globally available treatments for PCOS. After applying pre-determined inclusion criteria, 41 studies were included in this scoping review. The literature on the available treatments for PCOS revealed a wide range of therapeutics with evidence of reduction of symptoms and/or improvement in fertility status and pathological processes such as insulin resistance, hormone imbalance, obesity, inflammation, and infertility. Dozens of treatment options for PCOS have been identified, including new medications and modifications to existing treatment regimens. The hormonal drug Fezolinetant demonstrated effective suppression of hyperandrogenism. Drugs used to treat diabetes, such as Liraglutide, were found effective for weight loss. Green cardamom, cinnamon, and other supplements proved effective in treating metabolic dysfunction. Alternative approaches, such as osteopathic manipulative therapy and acupuncture, decreased sympathetic tone and androgen levels. This review provides a succinct overview of PCOS therapies that can be used by those with PCOS and their physicians everywhere. With a better understanding of their options, women with PCOS can become more involved in the decision-making process to improve their health. More research is needed on novel therapies that aim to reduce the primary pathogenesis of PCOS.

Effect of Choline Inositol and Metformin Combination Versus Metformin Alone on Ovarian Activities in PCOS Iraqi Women: A Cross Sectional Study

Abstract: Polycystic ovary syndrome (PCOS) is a predominant endocrine sickness disturbing females. It is marked via unequal menstrual cycles, hyper-androgenism, and polycystic ovarian morphology. Furthermore, PCOS is linked to several health issues, including insulin resistance and metabolic syndrome. PCOS management encompasses a range of strategies and treatments. Medications acting on hormones, including insulin sensitizers such as inositol and metformin, are commonly used to treat PCOS symptoms. Also choline is other potential therapies that could improve reproductive health. It has been suggested to be beneficial in various aspects of fertility, including endocrine disorders like polycystic ovarian syndrome (PCOS). Aim of the study: The current study aims to determine the effect of choline inositol and metformin combination versus metformin alone on ovarian. Materials and methods: This study was performed at the Maternity and Paediatrics Teaching Hospital in ALdiwaniyah Province, Iraq. The study involved a total of (150) patients at (18- &lt;40) years. A gynecologist uses Rotterdam criteria and ultrasound ovarian morphology in the selection of PCOS patients. The study consisted of several groups: G1 is a thirty women had received oral Metformin 500 mg bid during meal for last three months and served as metformin group. G2 is a thirty women had received choline inositol supplement 500/500 mg per- oral twice daily for last three months and served as the choline inositol supplement group. G3 is a thirty women had received choline inositol and metformin combination, they received with the same above dose for last three months and served as the choline inositol and metformin combination group . G4 is a thirty women who have not received any treatment for PCOS and served as new diagnosis PCOS group. Finally G5 is a thirty healthy women control group (control group). Characteristics included body mass index, type of period (regular, irregular ,amenorrhea ) were evaluated for all the participants. Furthermore, follicle and ovary volume were measured for all women .Additionally, serum hormonal levels [prolactin, (FSH), (LH), (TSH)], test were done. Results: There was no important alteration in the mean age, TSH and prolactin among the five groups. The results showed that metformin had significantly lowered in BMI but the addition choline inositol to metformin showed more significantly lowering in BMI but new PCOS group had higher significant BMI than other groups followed by choline inositol group. Rate of amenorrhea and rate of cycle irregularity stayed considerably upper in metformin grouping paralleled to choline inositol and choline inositol + metformin combination groups but this rate was more significantly higher in new PCOS compared to other groups. Metformin had significantly higher LH level compared to other groups but choline inositol + metformin and choline inositol groups had significantly lower LH level and there were no significance in the mean of LH between Choline inositol + metformin and choline inositol groups. Moreover, choline inositol + metformin group showed more significant FSH normal followed by metformin and new PCOS then by choline inositol and lastly control group. Choline inositol followed by metformin showed a significance in the mean of follicle and ovary volume but when adding choline inositol to metformin it showed more significant improvement in follicle and ovary volume ,so positive pregnancy was only seen in choline inositol + metformin as compared to other groups.

Polycystic ovary syndrome and type 1 diabetes - the current state of knowledge.

Type 1 diabetes mellitus (T1DM) is characterized by an increased prevalence of polycystic ovary syndrome (PCOS) with its negative metabolic consequences, including increased cardiovascular risk. Both diseases affect patients, significantly deteriorating the quality of life. During the treatment of patients with T1DM and PCOS, lifestyle modification and increased physical activity resulting in weight reduction should always be recommended. Pharmacological treatment should be applied in accordance with the current standards. In most of these patients metformin alone or with combined oral contraceptive pills could be considered for cycle regulation. In obese patients with T1DM and PCOS glucagon-like peptide-1 receptor agonists (GLP-1 Ras) (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptides (GIP)/GLP-1 RAs (tirzepatide) are regarded as a safe approach. Anti-androgens could also be considered especially to treat hirsutism and hyperandrogenism in women with PCOS. There are relatively limited evidence on anti-androgens in PCOS and we should consider use them in only selected cases. Some other substances may have a positive effect on patients with T1DM and PCOS include inositol, alpha-lipoic acid, folic acid, vitamins (B1, B6, B12, D, K, E, A), chromium and selenium compounds, as well as omega-3 fatty acids. The gut microbiome is also considered as a critical modulator of the predisposition to PCOS and T1DM and may be the future goal of the treatment. The proper treatment of PCOS will translate into a reduction in the severity of typical symptoms and also into the improvement in the metabolic control of diabetes and the patients' quality of life.

TIGAR relieves PCOS by inhibiting granulosa cell apoptosis and oxidative stress through activating Nrf2

This study aimed to elucidate the role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in polycystic ovary syndrome (PCOS). A rat model PCOS was constructed by subcutaneous injection with dehydroepiandrosterone (DHEA). Follicular atresia and reduced granular cells (GCs) in ovaries suggested successful modeling. The low expression of TIGAR was observed in ovarian tissue of PCOS rat. To explore the role of TIGAR in PCOS, lentivirus carrying the TIGAR were used to up-regulate TIGAR expression. TIGAR overexpression reduced the DHEA-induced increase of ovarian weight, the levels of estradiol (E2), and the ratio of luteinizing hormone/follicle-stimulating hormone (LH/FSH) in the serum, as well as improved the morphology of the follicle, especially increased the thickness of the GC layer, which attributed to the inhibition of apoptosis by TIGAR. In addition, high expression of TIGAR inhibited oxidative stress in ovaries of PCOS rat, as evidenced by decreased level of malondialdehyde (MDA), and reactive oxygen species (ROS), and enhanced activity of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Mechanically, Nrf2/OH-1 signal pathway was activated by TIGAR. The effect of TIGAR on PCOS were verified in the primary rat GCs treated with dihydrotestosterone, but also the rescue experiment was performed. Downregulation of Nrf2 reversed the effects of TIGAR, indicating that TIGAR suppressed oxidative stress and GC apoptosis by activating Nrf2/OH-1 pathway in PCOS. Finally, non-targeted metabolomics revealed that TIGAR might affect the energy metabolic pathway, thereby altering the metabolic profile of primary rat GCs. This study provided new insights into the prevention and treatment of PCOS.

Efficacy of physical activity in polycystic ovary syndrome treatment.

Physical activity (PA) is acknowledged as an important component of lifestyle therapy in the management of polycystic ovary syndrome (PCOS). The purpose of this current systematic review is to analyze recent literature assessing the role of PA and exercise interventions as potential treatment for PCOS. The recent literature published since 2022 has focused on understanding the specific benefits of different PA modalities on PCOS pathophysiology, suggesting that high intensity exercise may relay greater metabolic improvements, although results are still inconclusive; expanding our understanding of the impact PA has on a wider range of outcomes, including sleep, quality of life, inflammation, and DNA methylation; and recognizing barriers and limitations of implementing efficacious PA interventions for individuals with PCOS. Current literature supports a role for PA in improving PCOS-related cardiometabolic and reproductive outcomes; however, there is still a significant evidence gap of high-quality studies assessing optimal exercise regimens as well as strategies for implementing PA interventions in real-world settings for individuals with PCOS.

Piperine’s potential in treating polycystic ovarian syndrome explored through in-silico docking

Polycystic Ovarian Syndrome (PCOS) is a multifaceted metabolic and hormonal condition that impacts women in their procreative ages, identified by ovarian dysfunction, hyperandrogenaemia overweight and insulin insensitivity. The piperine, an important alkaloid compound of black pepper has shown promise in modulating various physiological processes. In this work, employed computational docking studies to explore the potential of piperine as a treatment for PCOS. Utilizing computational methods, we analyzed the binding interactions between piperine and key molecular targets implicated in PCOS pathogenesis, including hyperandrogenism, and “oligomenorrhea. The network pharmacology analysis report found 988 PCOS-related genes, 108 hyperandrogenism-related genes, and 377 oligomenorrhea-related genes, and we finally shortlisted 5 common genes in PCOS, hyperandrogenism, and “oligomenorrhea”: NR3C1, PPARG, FOS, CYP17A1, and H6PD. Our results reveal favorable binding affinities with PPARG (-8.34 Kcal/mol) and H6PD (-8.70 Kcal/mol) and interaction patterns, suggesting the potential of piperine to modulate these targets. Moreover, the reliability of the piperine-target interactions was revealed by molecular simulations studies. These findings support further experimental investigations to validate the therapeutic efficacy of piperine in PCOS management. The integration of computational approaches with experimental studies has the potential to lay the groundwork for the creation of new therapies specifically targeting PCOS and related endocrine disorders.

Polycystic ovary syndrome: new and promising treatment methods

Polycystic Ovary Syndrome (PCOS) - is a polygenic endocrine disorder caused by genetic, hormonal, and epigenetic factors. The importance of addressing PCOS lies in its prevalence, affecting approximately 10 to 13% of women, as well as the associated health conditions that can have a negative impact on women's lives, including infertility, dermatological manifestations of hyperandrogenism (such as hirsutism and acne), cardiovascular pathologies, metabolic disorders, and psychoemotional disorders. Currently, many theories of the development of this disease have been proposed, and as a consequence of methods of influencing and treating it. According to the clinical recommendations of the Ministry of Health of the Russian Federation, modifying the patient's lifestyle forms the basis of comprehensive therapy. We have analyzed about 60 articles on various dietary approaches to the treatment of PCOS, sourced from PubMed, Nature Reviews, Oxford Academic, Clinical Nutrition, EJOG, ScienceDirect, and MDPI. The Mediterranean diet, the DASH diet, the ketogenic diet and the low-carb diet have proven themselves the best. Also, it's necessary to add vitamin D, E, folic acid, calcium, various pro- and prebiotics to a woman's diet. Currently, the use of inositol and GPP-1 is becoming a promising method of PCOS therapy. According to the results of the analysis, a positive effect of diet therapy on the anthropometric and biochemical parameters was noted. Based on the analysis, a positive effect of diet therapy on anthropometric and biochemical parameters has been observed. It is crucial to consider the individual characteristics of each patient and not rely solely on drug therapy when approaching the treatment of PCOS.