Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.
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ABSTRACT:
SUBMITTER: Alesi S
PROVIDER: S-EPMC10424142 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.
Alesi Simon S Forslund Maria M Melin Johanna J Romualdi Daniela D Peña Alexia A Tay Chau Thien CT Witchel Selma Feldman SF Teede Helena H Mousa Aya A
EClinicalMedicine 20230809
<h4>Background</h4>Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clin ...[more]
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Project description:Polycystic ovary syndrome (PCOS) is a metabolic-reproductive-endocrine disorder that, while having a genetic component, is known to have a complex multifactorial etiology. As PCOS is a diagnosis of exclusion, standardized criteria have been developed for its diagnosis. The general consensus is that hyperandrogenism is the primary feature of PCOS and is associated with an array of physiological dysfunctions; excess androgens, for example, have been correlated with cytokine hypersecretion, adipocyte proliferation, and signaling pathway dysregulation. Another key feature of PCOS is insulin resistance, resulting in aberrant glucose and fatty acid metabolism. Additionally, the immune system plays a key role in PCOS. Hyperandrogenism stimulates some immune cells while it inhibits others, thereby disrupting the normal balance of immune cells and creating a state of chronic inflammation. This low-grade inflammation could contribute to infertility since it induces ovarian dysfunction. This dysregulated immune response in PCOS exhibits autoimmunity characteristics that require further investigation. This review paper examines the relationship between androgens and the immune response and how their malfunction contributes to PCOS.
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Project description:Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with hyperandrogenism present in up to 90% of affected women. Some evidence suggests a link between vitamin D deficiency and PCOS features via insulin resistance and inflammation. Our aim was to explore the relationship between biochemical markers of vitamin D status and androgens in women with PCOS. This cross-sectional study used bio-banked samples from 46 pre-menopausal women with PCOS (mean ± SD: age 30 ± 6 years; BMI 29 ± 6 kg/m2). We measured 25-hydroxyvitamin D (25[OH]D), vitamin D-binding protein (DBP), total testosterone, sex hormone-binding globulin (SHBG), and calculated the free androgen index (FAI) and bioavailable and free 25(OH)D. Fasting glucose and insulin were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) and body fat percentage was determined via dual energy x-ray absorptiometry. High-sensitivity C-reactive protein (hs-CRP) was measured as a marker of inflammation. DBP was positively associated with total 25(OH)D and expectedly, negatively associated with free 25(OH)D. There were no associations between vitamin D metabolites and total testosterone, SHBG or FAI, even after adjusting for age, body fat percentage, HOMA-IR and hs-CRP. We found no associations between vitamin D metabolites and androgens in women with PCOS. Studies that have identified a vitamin D-androgen link have largely relied on methodology with numerous pitfalls; future studies should exclusively use gold-standard measures to confirm these findings in this population.
| S-EPMC7282251 | biostudies-literature
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| S-BSST1412 | biostudies-other
Project description:ContextPolycystic ovary syndrome (PCOS), a common endocrine condition, is the leading cause of anovulatory infertility.ObjectiveGiven that common disease-susceptibility variants account for only a small percentage of the estimated PCOS heritability, we tested the hypothesis that rare variants contribute to this deficit in heritability.Design, setting, and participantsUnbiased whole-genome sequencing (WGS) of 80 patients with PCOS and 24 reproductively normal control subjects identified potentially deleterious variants in AMH, the gene encoding anti-Müllerian hormone (AMH). Targeted sequencing of AMH of 643 patients with PCOS and 153 control patients was used to replicate WGS findings.Main outcome measuresDual luciferase reporter assays measured the impact of the variants on downstream AMH signaling.ResultsWe found 24 rare (minor allele frequency < 0.01) AMH variants in patients with PCOS and control subjects; 18 variants were specific to women with PCOS. Seventeen of 18 (94%) PCOS-specific variants had significantly reduced AMH signaling, whereas none of 6 variants observed in control subjects showed significant defects in signaling. Thus, we identified rare AMH coding variants that reduced AMH-mediated signaling in a subset of patients with PCOS.ConclusionTo our knowledge, this study is the first to identify rare genetic variants associated with a common PCOS phenotype. Our findings suggest decreased AMH signaling as a mechanism for the pathogenesis of PCOS. AMH decreases androgen biosynthesis by inhibiting CYP17 activity; a potential mechanism of action for AMH variants in PCOS, therefore, is to increase androgen biosynthesis due to decreased AMH-mediated inhibition of CYP17 activity.
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| S-EPMC9433272 | biostudies-literature
Project description:BackgroundThe role of excess androgen in ovarian reserve remains unclear in patients with polycystic ovary syndrome (PCOS). Our study highlights the associations of serum androgen levels and ovarian reserve markers in PCOS and non-PCOS women.MethodsTotally 584 menstrual abnormalities women of 20-45 years were retrospectively evaluated at the Beijing Obstetrics and Gynecology Hospital between January 2021 to October 2021. The enrolled patients were classified into two groups: the PCOS group (n=288) and the non-PCOS group (n=296) based on the Rotterdam consensus for PCOS diagnosis. The serum androgens, including testosterone (T), free testosterone (FT, calculated), bioavailable testosterone (Bio-T, calculated), androstenedione (A2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) were assessed with an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The associations between the serum androgens and the hormone markers commonly used for evaluating ovarian reserve function, such as anti-mullerian hormone (AMH) and the ratio of luteinizing hormone (LH)/follicle stimulating hormone (FSH) were explored.ResultsThe serum T, FT, Bio-T, A2, DHT, DHEA, DHEAS, AMH and LH/FSH of the PCOS group were 51.7 ± 23.2 ng/dL/mL, 8.5 ± 5.0 pg/mL, 210.1 ± 127.7 pg/mL, 1.9 ± 0.8 ng/mL, 0.2 ± 0.1 ng/mL, 6.4 ± 4.2 ng/mL, 2431.0 ± 1030.7 ng/mL, 6.7 ± 3.8 ng/mL, and 1.8 ± 1.4 respectively, which were significantly higher than those in the non-PCOS group (p<0.05). In the group of PCOS patients, T and A2 levels were positively associated with AMH in both multivariate linear regression analysis and Pearson's correlation analysis. Similar but weaker associations were observed in the non-PCOS patients. In the PCOS patients with hyperandrogenemia (HA), the AMH level was significantly higher in the subjects with T increased than in the subjects with non-T androgen(s) increased (A2, DHT, DHEA or DHEAS).ConclusionsThe serum androgen levels are positively associated with ovarian reserve markers in both of the PCOS and the non-PCOS patients in our study. In the PCOS group, the highest AMH level was observed in the subjects with the T elevation subgroup, suggesting that T is more closely related with the increase of AMH when compared with other androgens investigated.
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Project description:Polycystic ovary syndrome (PCOS) is a common endocrine disorder predominantly affecting women of reproductive age. Clinical manifestations are diverse including hyperandrogenism, anovulation, infertility and increased risk of metabolic diseases besides psychosocial dysfunction. This review provides information on the problem of PCOS in India, its pathophysiology, genetics and an overview of current management options to instigate further research in this field. Prevalence of PCOS in India ranges from 3.7 to 22.5 per cent depending on the population studied and the criteria used for diagnosis. Abnormalities in leptin-adiponectin (adipocyte biology), oxidative stress and autoimmunity are among the mechanisms studied regarding pathogenesis of PCOS. Many candidate gene studies have shown associations with PCOS in various studies. Studies have consistently demonstrated the relationship between the well-known manifestation of hyperandrogenism among Indian PCOS women and the metabolic morbidities including insulin resistance, glucose intolerance and cardiovascular risk. Management of individual components of PCOS can be achieved by medications or surgical methods, though further clarification regarding pathogenesis of PCOS is needed to sharpen our therapeutic armamentarium.
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Project description:BackgroundPeople with polycystic ovary syndrome suffer from many symptoms and are at risk of developing diseases such as hypertension and diabetes in the future. Therefore, the importance of self-care doubles. It is mainly to modify the lifestyle, especially following the principles of healthy eating. The purpose of this study is to review artificial intelligence-based systems for providing management recommendations, especially food recommendations.Materials and methodsThis study started by searching three databases: PubMed, Scopus, and Web of Science, from inception until 6 June 2023. The result was the retrieval of 15,064 articles. First, we removed duplicate studies. After the title and abstract screening, 119 articles remained. Finally, after reviewing the full text of the articles and considering the inclusion and exclusion criteria, 20 studies were selected for the study. To assess the quality of articles, we used criteria proposed by Malhotra, Wen, and Kitchenham. Out of the total number of included studies, seventeen studies were high quality, while three studies were moderate quality.ResultsMost studies were conducted in India in 2021. Out of all the studies, diagnostic recommendation systems were the most frequently researched, accounting for 86% of the total. Precision, sensitivity, specificity, and accuracy were more common than other performance metrics. The most significant challenge or limitation encountered in these studies was the small sample size.ConclusionRecommender systems based on artificial intelligence can help in fields such as prediction, diagnosis, and management of polycystic ovary syndrome. Therefore, since there are no nutritional recommendation systems for these patients in Iran, this study can serve as a starting point for such research.
| S-EPMC11015675 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) is one of the most common disorders of reproductive endocrinology affecting women of reproductive age. Our study aims to explore the feasibility of a full-scale trial to evaluate the efficacy and safety of acupuncture for PCOS.MethodsThis study is a two-armed, parallel, multi-country, multi-center, pilot randomized controlled trial (RCT) for PCOS with oligomenorrhea. We will recruit 60 women aged 20 to 40 years with oligomenorrhea due to PCOS. The participants will be randomly assigned to acupuncture and control groups. The acupuncture group will undergo a total of 40 sessions for 16 weeks with usual care. The control group will be managed with usual care (regular meals, sufficient sleep, and appropriate exercise) only. The primary clinical outcome is mean change in menstrual frequency from baseline to 16 weeks and 32 weeks (follow-up) after the start of the trial. The secondary outcomes are menstrual period, levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total testosterone, LH/FSH ratio, antral follicle count and ovarian volume, body mass index, waist hip ratio, acne severity, and health-related quality of life questionnaire scores at 16 and 32 weeks after the start of the trial.DiscussionThis is the first protocol for multi-country, multi-center RCTs for PCOS in Korea and China. The control group in this study will be subjected to usual care (regular meals, enough sleep, and appropriate exercise). The results of this study will provide evidence for future clinical decisions and guidelines.This trial has been registered at ClinicalTrials.gov (Identifier: NCT04509817).
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