Materiały źródłowe

• #1 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10583117/

  Polycystic ovary syndrome arises as a result of polygenic susceptibility in combination with environmental influences that might include epigenetic alterations and in utero programming. […] Advances in genetics, metabolomics, and adipocyte biology have improved our understanding of key changes in neuroendocrine, enteroendocrine, and steroidogenic pathways, including increased gonadotrophin releasing hormone pulsatility, androgen excess, insulin resistance, and changes in the gut microbiome. […] An improved understanding of the pathogenesis of the disease might result in the development of new treatments and better patient outcomes. Recent studies have advanced our understanding of these pathophysiological processes. Neuroendocrine dysregulation leads to abnormal high frequency pulsatile secretion of gonadotrophin releasing hormone, and hypothalamic kisspeptin, neurokinin B, and dynorphin A neurons (so-called KNDy neurons) are integral regulators of this process.

• #2 Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing

  https://www.mdpi.com/1422-0067/23/2/583

  Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. […] Evidence suggests the role of different external and internal factors, including insulin resistance (IR), hyperandrogenism (HA), environmental factors, genetic, and epigenetics. […] Given that PCOS is a growing issue that is unfortunately followed by many unwanted complications and that available methods and medications are not 100% effective, it is essential to investigate its pathogenesis and find out new pharmacological targets carefully. […] This review discusses PCOS’s definition, diagnosis, and etiology, focusing on the pathogenesis and management of this syndrome. Internal and external factors contributing to PCOS have been comprehensively studied, and several commonly prescribed medications with their complete drug information are provided.

• #2 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10583117/

  Although increased production of ovarian and adrenal androgens contribute to hyperandrogenism, peripherally generated 11-oxygenated androgens are emerging as important predictors of metabolic risk. […] Together with advances in our understanding of adipocyte biology, insulin resistance, the gut microbiome, and insights from genome-wide association studies, these studies could improve our understanding of the pathogenesis of this disease. […] Polycystic ovary syndrome is characterised by increased pulse frequency of gonadotrophin releasing hormone and reduced negative feedback from sex steroids at the level of the hypothalamus. […] The pulse frequency of gonadotrophin releasing hormone is controlled by multiple upstream endocrine and neural factors, with a higher frequency favouring secretion of luteinising hormone and a lower frequency favouring secretion of follicle stimulating hormone.

• #3 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10583117/

  In women with polycystic ovary syndrome, raised levels of luteinising hormone cause excess production of ovarian thecal androgens, whereas relative deficiency of follicle stimulating hormone causes follicular arrest, polycystic ovarian morphology, and oligo-ovulation. […] The reduction in sex steroid feedback on release of gonadotrophin releasing hormone is thought to occur upstream of the hormone itself because gonadotrophin releasing hormone neurons do not have receptors for oestrogens or progesterone. […] Increased activity of ovarian 11-hydroxysteroid dehydrogenase type 1 (11-HSD1), which converts inactive cortisone to active cortisol, might also have a role in the pathogenesis of polycystic ovary syndrome. […] Raised circulating levels and ovarian expression of vascular endothelial growth factor also contribute to the hypervascular, hyperplastic appearance of the ovarian stroma and theca interna in polycystic ovary syndrome, and might contribute to increased ovarian androgen synthesis.

• #4 PCOS Part 1: Pathophysiology of PCOS – The ObG Project

  https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/

  PCOS represents an example of this. It is a disorder characterized by a collection of symptoms, and is prevalent in patients who present at infertility clinics, affecting 5-10% of women at reproductive age. […] In a woman with PCOS the HPO axis does not express normal functionality. The pulsatile hormone GnRH is altered, resulting in increased LH activity by the pituitary gland. This increase in LH increases theca cell stimulation, which produces androstenedione and testosterone, two androgens, and the resulting hyperandrogenic milieu of the ovary precludes normal follicular growth, maturation and ovulation. […] It remains unknown why PCOS occurs and whom it affects, but it is thought that genetics and environmental factors have a complex interplay in its emergence and clinical manifestations.

• #4 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10583117/

  Polycystic ovary syndrome was previously thought to be primarily a disease of excess production of androgens in the ovaries, but the adrenal glands and peripheral tissues are now considered important sources of androgens in patients with polycystic ovary syndrome. […] Increased concentrations of dehydroepiandrosterone sulphate, an almost exclusive product of the adrenal cortex, are apparent in 20-30% of patients with polycystic ovary syndrome. […] Changes in steroidogenesis, such as increased enzymatic activity of the 17-hydroxylase subunit of the cytochrome P450 enzyme, CYP17A1, might account for this hyper-responsiveness. […] Insulin resistance, and the consequent hyperinsulinism, have an important role in driving androgen synthesis in many endocrine tissues. […] Insulin acts as a co-gonadotrophin in the ovaries, impairs progesterone mediated inhibition of the gonadotrophin releasing hormone pulse generator, and facilitates synthesis of androgens in the adrenal glands by increasing adrenocorticotropic hormone stimulated steroidogenesis.

• #5 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities | BMJ Medicine

  https://bmjmedicine.bmj.com/content/2/1/e000548

  Although increased production of ovarian and adrenal androgens contribute to hyperandrogenism, peripherally generated 11-oxygenated androgens are emerging as important predictors of metabolic risk. […] Together with advances in our understanding of adipocyte biology, insulin resistance, the gut microbiome, and insights from genome-wide association studies, these studies could improve our understanding of the pathogenesis of this disease. […] High levels of androgens is a primary defect in polycystic ovary syndrome. […] Increased activity of ovarian 11-hydroxysteroid dehydrogenase type 1 (11-HSD1), which converts inactive cortisone to active cortisol, might also have a role in the pathogenesis of polycystic ovary syndrome. […] Polycystic ovary syndrome was previously thought to be primarily a disease of excess production of androgens in the ovaries, but the adrenal glands and peripheral tissues are now considered important sources of androgens in patients with polycystic ovary syndrome.

• #5 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10583117/

  Changes in white adipose tissue morphology and function is seen in women with polycystic ovary syndrome, including enlarged adipocytes, reduced lipoprotein lipase activity, and increased secretion of proinflammatory cytokines. […] Recent studies have implicated changes in the gut microbiome in the pathogenesis of polycystic ovary syndrome. […] Emerging evidence indicates that polycystic ovary syndrome might have its origins in utero, and thus could be subject to developmental programming and epigenetic modifications. […] Epigenetic mechanisms might also be involved in mediating susceptibility to polycystic ovary syndrome, with differential methylation patterns and microRNA expression detected in adipose tissue and ovarian tissue of patients with polycystic ovary syndrome compared with controls.

• #6 Pathophysiology of Polycystic Ovarian Syndrome | IntechOpen

  https://www.intechopen.com/chapters/79950

  The cumulative effect of modified protein, which are the product of mutated genes, along with various other factors like genetic inheritance and environment leads to complications in the case of PCOS. […] The genetic tendency for PCOS: There are many genes, which are responsible to cause PCOS. […] The critical genetic variations in PCOS across different ethnicities and their associated effects such as hyperandrogenism in women, insulin resistance, miscarriage, recurrent pregnancy loss, endometrial receptivity. […] Genes involved in PCOS are DENND1A, SHBG, THADA, FBN3, LHCGR, and INSR, etc. […] The initial step of steroidogenesis is the conversion of cholesterol into progesterone which is catalyzed by P450. […] The gene CYP11A which is located at 15q24 encodes P450. […] The CYP11A alleles also show the association with 5UTR.

• #7 Polycystic ovary syndrome; The role of androgen excess in disease pathogenesis and metabolic dysfunction | SFEBES2018 | Society for Endocrinology BES 2018 | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0059/ea0059mc1.1

  Polycystic ovary syndrome; The role of androgen excess in disease pathogenesis and metabolic dysfunction […] Insulin resistance and androgen excess, alongside anovulatory infertility, are the cardinal clinical and biochemical features of polycystic ovary syndrome (PCOS). […] Circulating androgen burden and metabolic dysfunction in PCOS are closely correlated, but an independent contribution of androgens per se to metabolic and other complications of PCOS remains poorly characterised. […] My work since 2012 has focused on delineating the distinct impact of androgens on metabolic function, with a particular focus on adipose tissue and insulin resistance. […] One of these enzymes, aldoketoreductase type 1 C3 (AKR1C3), activates the androgen precursor androstenedione to more potent testosterone.

• #8 Polycystic Ovary Syndrome (PCOS): Symptoms, Causes, and Treatment

  https://www.healthline.com/health/polycystic-ovary-disease

  Polycystic ovary syndrome is caused by an imbalance of androgens. […] Women with PCOS produce higher-than-normal amounts of male hormones. This hormone imbalance causes their body to skip menstrual periods and makes it harder for them to get pregnant. […] The lack of ovulation alters levels of estrogen, progesterone, FSH, and LH. Progesterone levels are lower than usual, while androgen levels are higher than usual. […] Doctors don’t know exactly what causes PCOS. They believe that high levels of male hormones prevent the ovaries from producing hormones and making eggs normally. […] Genes, insulin resistance, and inflammation have all been linked to excess androgen production. […] Up to 70 percent of women with PCOS have insulin resistance, meaning that their cells can’t use insulin properly.

• #9 Polycystic Ovary Syndrome: Pathophysiology and Controversies in Diagnosis

  https://www.mdpi.com/2075-4418/13/9/1559

  Polycystic ovarian syndrome (PCOS), described as an ovarian dysfunction, is a heterogeneous reproductive disorder with hormonal and metabolic implications. The pathogenesis of PCOS is multifactorial, involving an interplay among genetic, environmental, and trans-generational factors. The main hormones contributing to the development of PCOS are estrogen, androgen, and the anti-Müllerian hormone (AMH). Hyperandrogenism is a multifactorial PCOS pathology influenced by a combination of environmental and heritable elements. Hyperandrogenism can result from an imbalance in the hypothalamus–pituitary–ovarian axis signaling process, leading to excess secretion of insulin and luteinizing hormone. Another cause can be theca cells’ intrinsic dysfunction or diminished levels of cortisol that stimulate negative feedback on the hypothalamic–pituitary axis and elevate the synthesis of the hypothalamic adrenocorticotropic hormone after adrenal steroidogenesis stimulation, a leading factor in adrenal hyperandrogenism. Insulin resistance plays an influential role in the development and persistence of PCOS. This is mainly due to a defect in insulin receptors resulting from excessive serine phosphorylation and decreased tyrosine phosphorylation, which leads to a decrease in insulin activation of the phosphatidylinositol-3-kinase signaling pathway that activates glucose transport and consequently increases glucose levels. Women diagnosed with PCOS have higher AMH levels than normal women, which leads to the possibility of using AMH as a surrogate marker for the diagnosis of PCOS. The elevation is induced by an increase in the number of preantral follicles and small antral follicles, thus leading to increased secretion within each of these follicles.

• #10 Polycystic ovary syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Polycystic_ovary_syndrome

  Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of androgenic hormones, in particular testosterone, by either one or a combination of the following (almost certainly combined with genetic susceptibility): The release of excessive luteinizing hormone (LH) by the anterior pituitary gland […] through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus. A majority of women with PCOS have insulin resistance and/or are obese, which is a strong risk factor for insulin resistance, although insulin resistance is a common finding among women with PCOS in normal-weight women as well. Elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. Hyperinsulinemia increases GnRH pulse frequency, which in turn results in an increase in the LH/FSH ratio increased ovarian androgen production; decreased follicular maturation; and decreased SHBG binding. Furthermore, excessive insulin increases the activity of 17-hydroxylase, which catalyzes the conversion of progesterone to androstenedione, which is in turn converted to testosterone. The combined effects of hyperinsulinemia contribute to an increased risk of PCOS. PCOS may be associated with chronic inflammation, with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms. Similarly, there seems to be a relation between PCOS and an increased level of oxidative stress.

• #11 Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing

  https://www.mdpi.com/1422-0067/23/2/583

  The insulin’s influence on adipose tissue and inflammation is another essential PCOS pathogenesis topic. Insulin stimulates adipogenesis and lipogenesis and inhibits lipolysis, resulting in fat accumulation. […] Hyperinsulinemia contributes to PCOS by affecting the pituitary gland. Excessive insulin stimulates its receptors in the pituitary gland to release LH. […] The pathogenesis of PCOS is not fully understood, it is believed that different factors from epigenetic alterations to obesity, inflammation, and inactivity may aggravate this syndrome.

• #12 Systemic inflammation and insulin resistance in the pathogenesis of polycystic ovary syndrome – Rasin – Obstetrics and Gynecology

  https://journals.eco-vector.com/0300-9092/article/view/247466

  Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age, which affects 5-7% of the population and is associated with a broad spectrum of diseases: hypertension, dyslipidemia (DL), atherosclerosis, type 2 diabetes mellitus (T2DM), and gestational diabetes, increased risk of myocardial infarction, stroke, and higher cardiovascular and overall mortality rates. […] Inflammation, insulin resistance (IR), and hyperinsulinemia are permanent components of the pathogenesis of PCOS in obese women and in the majority of normal weight women due to the presence of a multitude of factors initiating systemic inflammation (SI) and IR. […] Gonzalez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012; 77(4): 300-5. […] Xiong Y.L., Liang X.Y., Yang X., Li Y., Wei L.N. Low-grade chronic inflammation in the peripheral blood and ovaries of women with polycystic ovarian syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 2011; 159(1): 148-50.

• #13 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Genetics-of-Polycystic-Ovary-Syndrome-(PCOS).aspx

  The severity of the condition depends on the levels of insulin and androgen. Excessive blood insulin level and subsequent insulin resistance ultimately lead to increased secretion of androgen from ovarian theca cells, which in turn causes increased production of free fatty acids from the visceral adipose tissue and disruption of insulin signaling. […] Excessive insulin secretion also causes a reduction in the hepatic biosynthesis of sex hormone-binding globulin and insulin-like growth factor binding protein, leading to further worsening of the condition. […] Aromatase is a member of the cytochrome P450 family that plays a crucial role in the conversion of androgens into estrogens. Mutations in several aromatase genes, including CYP11A1, CYP11B2, CYP17A1, CYP19A1, CYP1A1, CYP21A2, CYP3A7, have been reported to play roles in PCOS pathogenesis. These mutations mainly result in ovary dysfunction and elevation in blood androgen levels.

• #14 PCOS Part 1: Pathophysiology of PCOS – The ObG Project

  https://www.obgproject.com/2019/06/12/pcos-part-1-sensitive-care-of-the-pcos-patient/

  Although the diagnosis of insulin resistance (IR) is not part of the Rotterdam Criteria, it is highly prevalent in women with PCOS. […] In addition to insulin resistance, patients with PCOS and obesity may also suffer from what some term leptin resistance. […] Leptin resistance is considered an important risk factor for the pathogenesis of overweight and obesity, as the body remains insensitive to elevated levels and signals to the woman that she is still hungry/not satiated even after eating. […] Impaired leptin secretion not only affects body weight but can have a detrimental effect on ovulation and even fertilization in normal-weight PCOS patients.

• #15 Understanding the Pathogenesis of Polycystic Ovary Syndromelogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/na40708/2016/03/10/understanding-pathogenesis-polycystic-ovary-syndrome

  Understanding the Pathogenesis of Polycystic Ovary Syndrome […] Low levels of adiponectin might cause many of the abnormalities in this syndrome. […] These researchers might have identified deficient levels of circulating adiponectin as a pathogenetic factor in PCOS. This finding raises the possibility that treatment with adiponectin, or with agonists of the adiponectin receptors, might be successful in patients with PCOS.

• #16 Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9964744/

  Dysbiosis of the gut microbial community, caused by environmental risk factors, might be a potential pathogenic factor in the development and progression of PCOS. […] The dysregulation of the neuroendocrine system is thought to cause an imbalance in the hypothalamic-pituitary-ovarian (HPO) axis, which then leads to an excess of gonadotropin. […] An altered cortisol metabolism is another proposed mechanism that contributes to excess androgens in PCOS patients. […] Various genetic factors are associated with abnormal steroidogenesis. […] The gut microbiome is made up of approximately 10^13 to 10^14 microorganisms that collectively have almost 200 times more genes than the human genome, making it an organ on its own. […] Gut dysbiosis appears to be the root of the inflammation and alteration of gut permeability, which can then affect a host’s health.

• #17 Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9964744/

  Studies indicate that the diversity and structure of the gut microbiota in PCOS-affected women may be impacted by insulin resistance, sex hormone levels, and obesity. […] According to the DOGMA theory, poor-diet-induced gut microbiota dysbiosis may lead to an increase in the permeability of the gut mucosa, which in turn increases the passage of lipopolysaccharides (LPS) from Gram-negative colonic bacteria into the bloodstream. […] The resulting immune system activity disrupts insulin receptor function, elevating serum insulin levels, increasing the production of androgens in the ovaries, and interfering with normal follicle formation.

• #18 Association between Polycystic Ovary Syndrome and Gut Microbiota | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153196

  Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. […] The etiology and pathogenesis of PCOS remain unclear and may be multi-factorial, involving genetic, neuroendocrine and metabolic causes. Some researchers believe that PCOS may be not an ovarian disease but a metabolic disorder disease. […] What is consistent in PCOS is the production of excess androgens by the ovaries. Further studies are required to investigate the primary pathophysiology mechanisms underlying this syndrome. […] Tremellen and Pearce suggest that dysbiosis of gut microbiota (DOGMA) brought by a high fat-sugar diet in PCOS patients leads to an increase in the intestinal permeability. […] The DOGMA theory can account for the role of gut microbiota in the pathogenesis of PCOS.

• #19 Association between Polycystic Ovary Syndrome and Gut Microbiota | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153196

  The present study demonstrated that the microbiota composition of letrozole-induced PCOS rats and control rats were divided into different clusters, and PCOS group displayed a relatively high homology indicating common characteristics of PCOS. […] The results showed that with the copy number of Prevotella decrease the testosterone and androstenedione levels also decreased. […] These data suggested that FMT and Lactobacillus transplantation were helpful for the treatments of PCOS rats. […] In conclusion, we observed the gut microbiota shift in letrozole induced PCOS rat model and found that dysbiosis of gut microbiota was associated with sex hormone levels, estrus cycles and ovarian morphological changes. Furthermore, microbiota interventions by FMT and Lactobacillus transplantation could decrease the androgen level and increase the estrogen level in blood serum, improve ovarian disorder and estrus cycles in PCOS rats.

• #20 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Polycystic-Ovary-Syndrome-Pathogenesis.aspx

  There is a strong correlation between PCOS and resistance to insulin the body. […] It has been suggested that the raised levels of insulin alter the effect of gonadotropins and the function of the ovaries, leading to PCOS. […] The effect of insulin resistance in the pathogenesis of PCOS is amplified when a woman is overweight or obese. […] Another hormone called adiponectin that is involved in the control of lipid and glucose levels in the blood might also play a role in the pathogenesis of the condition. […] Research investigating a genetic link to the pathogenesis of PCOS has suggested an autosomal dominant pattern of inheritance in families with a history of the condition. […] Some studies have investigated the role of regulatory genes of the CYP17, CYP19, FST, and INSR enzymes in association with PCOS.

• #21 Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome | Nature Communications

  https://www.nature.com/articles/ncomms9464

  Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. […] We identify six signals for PCOS at genome-wide statistical significance, in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. […] Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI, higher insulin resistance and lower serum sex hormone binding globulin concentrations. […] This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk. […] The findings from our Mendelian randomization analyses have perhaps most immediate relevance for treatment and prevention, as these infer causal roles of greater BMI and insulin resistance.

• #22 Relationship between the characteristic traits of polycystic ovary syndrome and susceptibility genes | Scientific Reports

  https://www.nature.com/articles/s41598-020-66633-2

  Thus, these findings suggest that FSHB plays an important role in the pathogenesis of PCOS. […] Our results showed that rs11031006, near FSHB, was associated with multiple PCOS phenotypes, including free testosterone and LH levels. […] Collectively, FSHB variants are closely associated with hyperandrogenaemia and higher LH levels in women with PCOS. […] Therefore, hyperandrogenism, insulin resistance, and the FSH/LH axis are closely related to each other, exacerbating PCOS pathogenesis and related clinical features. […] In conclusion, we identified that the FSHB gene was associated with free testosterone and LH levels in Korean PCOS women but not in control women. This relationship suggests that FSHB may play an important role in PCOS development by altering free testosterone and LH levels.

• #23

  https://www.ijrcog.org/index.php/ijrcog/article/view/9594

  Development of polycystic ovary syndrome: involvement of genetic and environmental factors. […] The relationship between maternal and umbilical cord androgen levels and polycystic ovary syndrome in adolescence: a prospective cohort study. […] Premature pubarche, ovarian hyperandrogenism, hyperinsulinism and the polycystic ovary syndrome: from a complex constellation to a simple sequence of prenatal onset.

• #24 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities | BMJ Medicine

  https://bmjmedicine.bmj.com/content/2/1/e000548

  Insulin resistance, and the consequent hyperinsulinism, have an important role in driving androgen synthesis in many endocrine tissues. […] Changes in white adipose tissue morphology and function is seen in women with polycystic ovary syndrome, including enlarged adipocytes, reduced lipoprotein lipase activity, and increased secretion of proinflammatory cytokines. […] Recent studies have implicated changes in the gut microbiome in the pathogenesis of polycystic ovary syndrome. […] Emerging evidence indicates that polycystic ovary syndrome might have its origins in utero, and thus could be subject to developmental programming and epigenetic modifications.

• #25 Physiopathology of polycystic ovary syndrome in endocrinology, metabolism and inflammation | Journal of Ovarian Research | Full Text

  https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-025-01621-6

  Elevated androgen levels activate the endoplasmic reticulum (ER) stress response in granulosa cells, ultimately leading to cellular apoptosis through death receptor 5 (DR5). […] These findings highlight the apoptotic effects of androgens on granulosa cells in PCOS, demonstrating that elevated androgen levels are a significant factor in reproductive health issues and increase the risk of PCOS development in offspring. […] Despite incomplete elucidation of the precise pathophysiological mechanisms underlying PCOS, substantial evidence indicates that a complex interplay between chronic low-grade inflammation and the concurrent expression of proinflammatory and anti-inflammatory cytokines may play a crucial role in the onset and progression of this disorder. […] The 2023 international evidence-based guidelines in PCOS as well as underscore the potential association between metabolic abnormalities in patients with PCOS and the presence of chronic low-grade inflammation.

• #26 Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment | Journal of Ovarian Research | Full Text

  https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-022-01091-0

  Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overabundance of androgens; it affects 620% of women of reproductive age. […] PCOS involves various pathophysiological factors, and affected women usually have significant insulin resistance (IR), which is a major cause of PCOS. […] IR and compensatory hyperinsulinaemia (HI) are considered major drivers of PCOS pathophysiology and are involved in the development of hyperandrogenaemia and reproductive dysfunction by various mechanisms. […] The root cause of IR in PCOS is largely unknown and the underlying mechanism remains to be elucidated. […] Therefore, recognizing the strong influence of IR on the occurrence and development of PCOS, accurate assessment of insulin sensitivity in the early stages of PCOS, and effective intervention on IR are essential to reduce the risk of long-term complications.

• #27

  https://link.springer.com/article/10.1007/s13668-023-00479-8

  PCOS is a multifactorial syndrome in which genetic and environmental factors contribute to uncontrolled ovarian steroidogenesis, aberrant insulin signaling, and excessive oxidative stress. An intrinsic defect in theca cells could partially explain hyperandrogenemia in PCOS patients; women with PCOS, indeed, present theca cells which, despite the absence of trophic factors, can secrete high levels of androgens due to the intrinsic activation of steroidogenesis. […] A reduced insulin sensitivity, attributable to a post-receptor binding defect with an alteration in the gene expression of some genes involved in insulin signaling pathways, has also been identified as an intrinsic component of PCOS, regardless of obesity presence. […] Furthermore, PCOS syndrome has been associated to an increase in glycol-oxidative stress secondary to mitochondrial dysfunction, able to induce IR and hyperandrogenism in patients with PCOS.

• #28 Pathophysiology of Polycystic Ovarian Syndrome | IntechOpen

  https://www.intechopen.com/chapters/79950

  The gene CYP19 helps to converts the androgen into estrogen. […] The deficiency of aromatase enzyme mostly occur in those people whose is having high androgen level and this aromatase activity is decreased in follicles because as compared to normal follicles PCOS follicles having estradiol which lowers the aromatase stimulation bioactivity and the excess level of androgens leads to improper development of follicles.

• #29 Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9964744/

  Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. […] Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. […] Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. […] The pathophysiology of PCOS is chiefly concerned with hormonal imbalance, chronic low-grade inflammation, insulin resistance, and hyperandrogenism, which impair folliculogenesis and increase the risk of related comorbidities, such as endometrial cancer and type II diabetes. […] A range of environmental factors, including geography, diet and nutrition, socioeconomic status, and environmental pollutants, are possibly contributing to the development, occurrence, and management of PCOS.

• #30 Obesity and Polycystic Ovary Syndrome

  https://www.jomes.org/journal/view.html?uid=1071&vmd=Full

  The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance. […] Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance. Additionally, obesity contributes to polycystic ovary syndrome by facilitating the conversion of precursor hormones to testosterone within adipose cells. Moreover, obesity can lead to relative hyperandrogenemia, which is marked by lower levels of sex hormone binding globulin and increased availability of free testosterone to target tissues. Also, obesity affects the secretion of gonadotropins, resulting in heightened luteinizing hormone secretion or increased sensitivity of thecal cells to luteinizing hormone.

• #31 Bioinformatics analysis of the molecular mechanism of obesity in polycystic ovary syndrome | Aging

  https://www.aging-us.com/article/202938/text

  Obesity is an important part of polycystic ovary syndrome (PCOS) pathologies. […] The present study identified CHRDL1 as a candidate gene responsible for the obesity of PCOS patients. […] The expression of CHRDL1 was significantly higher in obesity PCOS cases than the BMI matched healthy controls. […] The gene CHRDL1 is found broadly expressed in fat, prostate and 15 other tissues, acts as an antagonist of bone morphogenetic protein 4 (BMP4). […] The role of CHRDL1 in PCOS and metabolism is rarely investigated. […] The present study aimed to identify the potential genes responsible for the obesity status in PCOS patients. […] The BMP4 protein has been linked with both obesity and PCOS, which may be responsible for the obesity status of PCOS cases. […] In summary, the present study identified the gene CHRDL1 that may be responsible for the obesity of PCOS patients, but not for non-PCOS cases. It was also suggested that CHRDL1 might function as an inhibitor of the BMP4 signalling or via regulation of IGF1.

• #32 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Polycystic-Ovary-Syndrome-Pathogenesis.aspx

  The pathogenesis of polycystic ovary syndrome (PCOS) is not precisely known. There are several mechanisms that have been suggested to play a role in the pathogenesis of PCOS, including hormonal imbalance, insulin resistance, and genetic inheritance. […] PCOS is associated with abnormal production and metabolism of hormones, such as androgens and estrogen, in the body. […] Some research has suggested that the secretion of luteinizing hormone (LH) from the anterior pituitary gland increases the stimulatory effect on the ovarian theca cells and may lead to the raised levels of androgenic hormones and irregular or absent ovulation. […] Some research has also linked the CYP450 C17 enzyme to PCOS as the rate-limiting step for the synthesis of androgenic hormones such as testosterone in the body.

• #33 Polycystic ovary syndrome: pathophysiology and therapeutic opportunities | BMJ Medicine

  https://bmjmedicine.bmj.com/content/2/1/e000548

  Polycystic ovary syndrome arises as a result of polygenic susceptibility in combination with environmental influences that might include epigenetic alterations and in utero programming. […] Advances in genetics, metabolomics, and adipocyte biology have improved our understanding of key changes in neuroendocrine, enteroendocrine, and steroidogenic pathways, including increased gonadotrophin releasing hormone pulsatility, androgen excess, insulin resistance, and changes in the gut microbiome. […] An improved understanding of the pathogenesis of the disease might result in the development of new treatments and better patient outcomes. Recent studies have advanced our understanding of these pathophysiological processes. Neuroendocrine dysregulation leads to abnormal high frequency pulsatile secretion of gonadotrophin releasing hormone, and hypothalamic kisspeptin, neurokinin B, and dynorphin A neurons (so-called KNDy neurons) are integral regulators of this process.

• #34 Research Progress in the Pathogenesis of Polycystic Ovary Syndrome

  https://ykxb.scu.edu.cn/en/article/doi/10.12182/20240760208

  Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrine disorders. […] The pathogenic mechanisms of PCOS remain unclear, involving key aspects such as the regulation of hypothalamic-pituitary function, ovarian cellular functions, androgen levels, and insulin resistance. […] Herein, we summarized the latest findings on the pathogenesis of PCOS from the perspectives of the genetic background, intrauterine development, neuroendocrine function, inflammatory factors, gut microbiome, and environmental factors.

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