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American Journal of Reproductive... Oct 2023Polycystic ovary syndrome (PCOS) is a disease with endocrine and metabolic disorders. The main symptoms are hyperandrogenemia (HA), insulin resistance (IR), and... (Review)
Review
Polycystic ovary syndrome (PCOS) is a disease with endocrine and metabolic disorders. The main symptoms are hyperandrogenemia (HA), insulin resistance (IR), and ovulation disorder. However, the pathogenesis and pathophysiological process of these major symptoms in PCOS are still not well defined. In recent studies, the chronic low-grade inflammatory state has become one of the factors affecting PCOS. Some alterable immune factors in PCOS, such as interleukin-15 and interleukin-1, have been identified to be related to androgen synthesis and insulin resistance in PCOS. In addition, a disturbed immune microenvironment in the ovary leads to impaired follicular growth and ovulation. Previous studies have roughly reviewed the relationship between immunity and PCOS. However, the link between the different clinical manifestations of PCOS and immunity has not been well explored and analyzed. The clinical presentation of each patient is diverse, and symptomatic treatment is mainly used. Therefore, this article reviews several representative immunological factors that affect these three symptoms to explore the underlying mechanism, which will be beneficial for developing new treatment strategies.
Topics: Female; Humans; Polycystic Ovary Syndrome; Insulin Resistance; Ovulation; Tumor Microenvironment
PubMed: 37766399
DOI: 10.1111/aji.13780 -
Drug Discovery Today Dec 2023Polycystic ovary syndrome (PCOS) prevails in approximately 33% of females of reproductive age globally. Although the root cause of the disease is unknown, attempts are... (Review)
Review
Polycystic ovary syndrome (PCOS) prevails in approximately 33% of females of reproductive age globally. Although the root cause of the disease is unknown, attempts are made to clinically manage the disturbed hormone levels and symptoms arising due to hyperandrogenism, a hallmark of PCOS. This review presents detailed insights on the etiology, risk factors, current treatment strategies, and challenges therein. Medicinal agents currently in clinical trials and those in the development pipeline are emphasized. The significance of the inclusion of herbal supplements in PCOS and the benefits of improved lifestyle are also explained. Last, emerging therapeutic targets for treating PCOS are elaborated. The present review will assist the research fraternity working in the concerned domain to access significant knowledge associated with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Dietary Supplements; Risk Factors
PubMed: 37935329
DOI: 10.1016/j.drudis.2023.103821 -
Life Sciences Dec 2023Polycystic Ovary Syndrome (PCOS) and osteoporosis, though seemingly unrelated, exhibit intricate connections influenced by genetic and epigenetic factors. PCOS,... (Review)
Review
Polycystic Ovary Syndrome (PCOS) and osteoporosis, though seemingly unrelated, exhibit intricate connections influenced by genetic and epigenetic factors. PCOS, characterized by elevated androgen levels, insulin resistance, and increased body weight, has historically been considered protective against bone fragility disorders. However, emerging research suggests that chronic inflammation, prevalent in PCOS, can adversely affect bone health. Studies have demonstrated variable bone mineral density loss in PCOS, often associated with leptin resistance and hyperinsulinemia. Key genes such as INS, IGF1, CTNNB1, AKT1, and STAT3 play pivotal roles in the complex interplay between PCOS and osteoporosis, influencing insulin signaling, oxidative stress, and inflammatory pathways. Oxidative stress, a prominent element in PCOS, can lead to osteoporosis through hormonal imbalances, chronic inflammation, insulin resistance, and lifestyle factors. The insulin signaling pathway also significantly impacts both conditions by contributing to hormonal imbalances and bone health alterations. This intricate network of genetic and epigenetic factors underscores the need for a deeper understanding of their interrelationships. Thus, this review elucidates the multifaceted genetic, epigenetic, and inflammatory connections between PCOS and osteoporosis, highlighting their implications for bone health management in individuals with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Insulin Resistance; Hyperandrogenism; Insulin; Osteoporosis; Inflammation
PubMed: 37981226
DOI: 10.1016/j.lfs.2023.122280 -
International Journal of Molecular... Aug 2023Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic... (Review)
Review
Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease, all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under the transcriptional regulation of both the nuclear and mitochondrial genome to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, as well as the dynamics that regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted, the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function, causing disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs, including the ovary (oocytes and granulosa cells), uterus, placenta, and circulation, causing reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in the transgenerational transmission of PCOS and metabolic disorders.
Topics: Animals; Female; Pregnancy; Humans; Polycystic Ovary Syndrome; Fertility; Cell Death; Genitalia
PubMed: 37685928
DOI: 10.3390/ijms241713123 -
Diabetes/metabolism Research and Reviews Sep 2023Polycystic ovary syndrome (PCOS) is a complex endocrinopathy affecting many women of reproductive age. Although its physiology is poorly understood, hyperandrogenemia... (Review)
Review
Polycystic ovary syndrome (PCOS) is a complex endocrinopathy affecting many women of reproductive age. Although its physiology is poorly understood, hyperandrogenemia and insulin resistance play a pivotal role in this complex syndrome, predisposing patients to a variety of cardiovascular and metabolic modalities. Current therapeutic options, including lifestyle modifications and medications, often do not satisfactorily improve clinical outcomes. SGLT2 inhibitors (SGLT-2i) are a novel option which can potentially improve many hormonal and metabolic parameters for patients with PCOS, though the net cardiovascular effects remain under investigation in this population of patients with PCOS. Overall, the use of SGLT-2i may be associated with beneficial somatometric, metabolic and hormonal outcomes of PCOS. To date, all available studies have recorded body mass index, waist and hip circumference, and fat mass reductions, improved insulin and androgen levels, and reduced blood pressure. The aim of the present review is to summarise PCOS-related manifestations and mechanisms leading to cardiovascular disease, to explore the cardiometabolic impact of SGLT2i on PCOS, and to critically analyse the cardiometabolic and hormonal outcomes of the recent studies on the use of SGLT2i in women with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Sodium-Glucose Transporter 2 Inhibitors; Insulin Resistance; Insulin; Cardiovascular Diseases
PubMed: 37392147
DOI: 10.1002/dmrr.3682 -
BMC Pediatrics Aug 2023Prader-Willi syndrome (PWS) is a genetic disorder involving multiple systems, with an incidence of about 1/10000-25000. Ovarian torsion (OT) is not commonly found in...
BACKGROUND
Prader-Willi syndrome (PWS) is a genetic disorder involving multiple systems, with an incidence of about 1/10000-25000. Ovarian torsion (OT) is not commonly found in children. Ovarian cyst acts as one of the primary factors resulting in OT. While ovarian cyst torsion with Prader-Willi Syndrome has not been reported before.
CASE PRESENTATION
A 12-years old female was admitted to Emergency Department of our hospital with the chief complaint of abdominal pain. The outcomes of physical examination revealed the height of 150 cm, weight of 103 kg, BMI of 45.77 kg/m. The patient manifested the special facial features, an obese body, with the abdomen distended into a spherical shape. The fat accumulation in the abdomen significantly embarrassed the palpation. The abdominal CT scan indicated a huge cystic mass in the abdominal cavity, sized about 138 mm × 118 mm. According to medical history, the patient was born with low crying and hypotonia, who has developed the uncontrollable eating behavior since 3-years old. These abnormalities led to a speculation of PWS syndrome, so a genetic test was performed and finally confirmed it, concluding a torsion of ovarian cyst with PWS. With the multidisciplinary consultation, a careful treatment strategy containing the control of blood pressure and blood sugar, coenzyme Q10 was administrated to nourish the myocardium and the application of Growth Hormone was developed. All the above preoperative treatments have brought great benefits to patients. Thus promising the successful completion of operation. The postoperative follow-up till now indicated that the abdominal incision was well healed, without operative complications.
CONCLUSIONS
This may be the first case report. In the treatment of ovarian cyst torsion, PWS syndrome requires fully consideration, as the latter can lead to multisystem abnormalities, especially the relation to perioperative management, and even fatalities. Genetic testing should be conducted early when PWS was suspected, accompanied with adequate preparation for the perioperative period, the follow-ups of patients should be maintained for a long time after surgery.
Topics: Humans; Female; Child; Ovarian Cysts; Prader-Willi Syndrome; Abdominal Pain; Muscle Hypotonia; Obesity; Human Growth Hormone
PubMed: 37553631
DOI: 10.1186/s12887-023-04223-7 -
BMJ (Clinical Research Ed.) Jul 2023Gestational diabetes mellitus (GDM) and polycystic ovarian syndrome (PCOS) represent two of the highest risk factors for development of type 2 diabetes mellitus in young... (Review)
Review
Gestational diabetes mellitus (GDM) and polycystic ovarian syndrome (PCOS) represent two of the highest risk factors for development of type 2 diabetes mellitus in young women. As these increasingly common conditions generally affect younger women, early detection of dysglycemia is key if preventative measures are to be effective. While international guidance recommends screening for type 2 diabetes, current screening strategies suffer from significant challenges.First, guidance lacks consensus in defining which tests to use and frequency of monitoring, thereby sending mixed messages to healthcare professionals.Second, conformity to guidance is poor, with only a minority of women having tests at the recommended frequency (where specified). Approaches to improve conformity have focused on healthcare related factors (largely technology driven reminder systems), but patient factors such as convenience and clear messaging around risk have been neglected.Third, and most critically, current screening strategies are too generic and rely on tests that become abnormal far too late in the trajectory towards dysglycemia to offer opportunities for effective preventative measures. Risk factors show wide interindividual variation, and insulin sensitivity and β cell function are often abnormal during pre-diabetes stage, well before frank diabetes.New, consistent, targeted screening strategies are required that incorporate early, prevention focused testing and personalised risk stratification.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Polycystic Ovary Syndrome; Diabetes Mellitus, Type 2; Risk Factors; Prediabetic State
PubMed: 37402524
DOI: 10.1136/bmj-2022-071675 -
Journal of Ovarian Research Nov 2023Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovarian cysts, high androgen levels, and irregular menstruation. The causality between PCOS...
Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovarian cysts, high androgen levels, and irregular menstruation. The causality between PCOS and breast cancer (BC) has been widely discussed as they share a significant intersection in clinical manifestations. Previous epidemiological studies have not provided consistent conclusions in association between PCOS and BC, while mendelian randomization (MR) analyses have confirmed the causality between PCOS and estrogen receptor-positive breast cancer (ER + BC), but among a series of clinical manifestations resulting from PCOS, which related traits mediate the causal effect remains unknown. In this study, we conducted multivariable mendelian randomization (MVMR) analysis to explore the potential mediator variables in the mechanism linking PCOS to distinct subtypes of BC, and calculated the mediating effects proportion. We analyzed 13 PCOS-related traits and found that age at menopause may mediate PCOS-induced ER + BC (with -4.82% proportion) with a weak protective effect through the repair of DNA double-strand breaks by homologous recombination. This study helps to better comprehend the shared mechanisms contributing to the development of both PCOS and BC, and to screen high-risk populations for BC and take appropriate preventive measures.
Topics: Female; Humans; Polycystic Ovary Syndrome; Mendelian Randomization Analysis; Breast Neoplasms; Risk Factors; Menstruation Disturbances
PubMed: 37957709
DOI: 10.1186/s13048-023-01306-y -
EBioMedicine Nov 2023Polycystic ovary syndrome (PCOS) is the most common endocrine disorder leading to anovulatory infertility. Abnormalities in the central neuroendocrine system governed by...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder leading to anovulatory infertility. Abnormalities in the central neuroendocrine system governed by gonadotropin-releasing hormone (GnRH) neurons might be related to ovarian dysfunction in PCOS, although the link in this disordered brain-to-ovary communication remains unclear. Here, we manipulated GnRH neurons using chemogenetics in adult female mice to unveil whether chronic overaction of these neurons would trigger PCOS-like hormonal and reproductive impairments.
METHODS
We used adult Gnrh1 female mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in hypophysiotropic GnRH neurons. Chronic chemogenetic activation protocol was carried out with clozapine N-oxide (CNO) i.p. injections every 48 h over a month. We evaluated the reproductive and hormonal profile before, during, and two months after chemogenetic manipulations.
FINDINGS
We discovered that the overactivation of GnRH neurons was sufficient to disrupt reproductive cycles, promote hyperandrogenism, and induce ovarian dysfunction. These PCOS features were detected with a long-lasting neuroendocrine dysfunction through abnormally high luteinizing hormone (LH) pulse secretion. Additionally, the GnRH-R blockade prevented the establishment of long-term neuroendocrine dysfunction and androgen excess in these animals.
INTERPRETATION
Taken together, our results show that hyperactivity of hypothalamic GnRH neurons is a major driver of reproductive and hormonal impairments in PCOS and suggest that antagonizing the aberrant GnRH signaling could be an efficient therapeutic venue for the treatment of PCOS.
FUNDING
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement n◦ 725149).
Topics: Humans; Female; Mice; Animals; Polycystic Ovary Syndrome; Luteinizing Hormone; Gonadotropin-Releasing Hormone; Neurons
PubMed: 37898094
DOI: 10.1016/j.ebiom.2023.104850 -
Endocrinology and Metabolism Clinics of... Sep 2023Polycystic ovary syndrome (PCOS) affects around 10% of women in the reproductive age group and is characterized by ovulatory dysfunction, hyperandrogenism, and/or... (Review)
Review
Polycystic ovary syndrome (PCOS) affects around 10% of women in the reproductive age group and is characterized by ovulatory dysfunction, hyperandrogenism, and/or polycystic ovarian morphology. PCOS is highly associated with metabolic-associated fatty liver disease (MAFLD) as both diseases share common risk factors. At the time of diagnosis of PCOS, screening for MAFLD is necessary because most patients with MAFLD are asymptomatic. The importance of early detection of MAFLD in patients with PCOS is that a timely intervention in patients with steatosis or steatohepatitis can reduce the probability of liver disease progression.
Topics: Humans; Female; Polycystic Ovary Syndrome; Non-alcoholic Fatty Liver Disease; Risk Factors; Hyperandrogenism; Insulin Resistance
PubMed: 37495343
DOI: 10.1016/j.ecl.2023.01.005