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International Journal of Women's Health 2023Explore the causal relationship between the ovarian cyst and depression using a two-sample Mendelian randomization approach (MR).
OBJECTIVE
Explore the causal relationship between the ovarian cyst and depression using a two-sample Mendelian randomization approach (MR).
METHODS
Based on data pooled from genome-wide association studies, genetic variants of the ovarian cyst and depression were selected as instrumental variables, as well as the Mendelian randomization analysis was conducted using inverse variance weighted (IVW) as the main analysis method and MR-Egger regression analysis, MR-PRESSO and other sensitivity analysis methods as supplements.
RESULTS
The IVW analysis showed a direct causal association between ovarian cysts and depression (OR=1.040; 95% CI: 1.003, 1.078; p=0.031). Meantime, there was a causal effect of genetically predicted depression on ovarian cysts (OR=1.327.; 95% CI: 1.197, 1.470; p<0.001). Sensitivity analyses such as MR-Egger regression analysis and MR-PRESSO indicated that the IVW results were robust and reliable.
CONCLUSION
This study suggested since ovarian cysts and female depression are mutually causal, the comorbidity of ovarian cysts and depression in women should be actively attended to and given appropriate prevention and treatment besides the diagnosis and treatment of depression or ovarian cysts.
PubMed: 38020935
DOI: 10.2147/IJWH.S415640 -
Frontiers in Endocrinology 2023Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no... (Review)
Review
Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no cure for PCOS, and current treatments primarily alleviate its symptoms due to a poor understanding of its etiology. Compelling evidence suggests that hyperandrogenism is not just a primary feature of PCOS. Instead, it may be a causative factor for this condition. Thus, figuring out the mechanisms of androgen synthesis, conversion, and metabolism is relatively important. Traditionally, studies of androgen excess have largely focused on classical androgen, but in recent years, adrenal-derived 11-oxygenated androgen has also garnered interest. Herein, this Review aims to investigate the origins of androgen excess, androgen synthesis, how androgen receptor (AR) signaling mediates adverse PCOS traits, and the role of 11-oxygenated androgen in the pathophysiology of PCOS. In addition, it provides therapeutic strategies targeting hyperandrogenism in PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Androgens; Phenotype
PubMed: 38152131
DOI: 10.3389/fendo.2023.1273542 -
Biomedicine & Pharmacotherapy =... Oct 2023The NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in the innate immune system and is a three-part macromolecular complex comprising the NLRP3... (Review)
Review
The NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in the innate immune system and is a three-part macromolecular complex comprising the NLRP3 protein, apoptosis-associated speck-like protein containing a CARD (ASC) and the cysteine protease pro-caspase-1. When the NLRP3 inflammasome is activated, it can produce interleukin (IL)- 1β and IL-18 and eventually lead to inflammatory cell pyroptosis. Related studies have demonstrated that the NLRP3 inflammasome can induce an immune response and is related to the occurrence and development of gynecological diseases, such as endometriosis, polycystic ovary syndrome and breast cancer. NLRP3 inflammasome inhibitors are beneficial for maintaining cellular homeostasis and tissue health and have been found effective in targeting some gynecological diseases. However, excessive inhibitor concentrations have been found to cause adverse effects. Therefore, proper control of NLRP3 inflammasome activity is critical. This paper summarizes the structure and function of the NLRP3 inflammasome and highlights the therapeutic potential of targeting it in gynecological diseases, such as endometriosis, polycystic ovary syndrome and breast cancer The application of NLRP3 inflammasome inhibitors is also discussed.
Topics: Female; Humans; Endometriosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Polycystic Ovary Syndrome; Genital Diseases, Female
PubMed: 37660654
DOI: 10.1016/j.biopha.2023.115393 -
Journal of Translational Medicine Feb 2024Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women's...
BACKGROUND
Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women's reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear.
METHODS
We established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS).
RESULTS
The HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures.
CONCLUSIONS
Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.
Topics: Female; Humans; Animals; Mice; Polycystic Ovary Syndrome; Sucrose; Diabetes Mellitus, Type 2; Reproduction; Diet; Gene Expression Profiling; Diet, High-Fat
PubMed: 38347623
DOI: 10.1186/s12967-024-04952-y -
Revista de La Facultad de Ciencias... Dec 2023The paraovarian or paratubarian cysts are both situated in the broad ligament between the ovary and fallopian tube. The diagnosis of adnexal torsion is challenging...
The paraovarian or paratubarian cysts are both situated in the broad ligament between the ovary and fallopian tube. The diagnosis of adnexal torsion is challenging since both symptoms and physical examination are nonspecific. In most cases, the patient presents abdominal pain, followed by nausea and vomiting. Imaging tests, such as ultrasound, are very useful to elucidate the cause of the symptoms in those patients.
Topics: Female; Humans; Ovarian Torsion; Cysts; Abdominal Pain
PubMed: 38150207
DOI: 10.31053/1853.0605.v80.n4.40830 -
Endocrine Regulations Jan 2023Hypothalamic-pituitary gonadal (HPG) axis is responsible for the development and regulation of the female reproductive system. In polycystic ovary syndrome (PCOS), there... (Review)
Review
Hypothalamic-pituitary gonadal (HPG) axis is responsible for the development and regulation of the female reproductive system. In polycystic ovary syndrome (PCOS), there is a disturbance in the HPG axis. Kisspeptin, a neuropeptide produced by the KISS1 gene, plays a vital role in the regulation of HPG axis by binding with its receptors KISS1R/GPR54, and stimulates gonadotropin secretion from the hypothalamus into pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Polymorphisms or mutations in the KISS1 gene can cause disturbance in the kisspeptin signaling pathway and is thought to disrupt HPG axis. Altered signaling of kisspeptin can cause abnormal secretion of GnRH pulse, which leads to increased LH/FSH ratio, thereby affecting androgen levels and ovulation. The increased levels of androgen worsen the symptoms of PCOS. In the present article, we review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS. The goal of this review article is to provide an overview and metabolic profile of kisspeptin in PCOS patients and the expression of kisspeptin in PCOS animal models. In the present article, we also review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS.
Topics: Animals; Female; Humans; Polycystic Ovary Syndrome; Kisspeptins; Androgens; Luteinizing Hormone; Follicle Stimulating Hormone
PubMed: 38127687
DOI: 10.2478/enr-2023-0032 -
Frontiers in Endocrinology 2023Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with...
INTRODUCTION
Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with estrogen levels within the normal range and can be characterized by oligo-/anovulation resulting in decreased progesterone levels. It is suggested that decreased progesterone levels may lead to more autoimmune diseases in women with PCOS. In addition, it is often claimed that there is an association between hyperprolactinemia and PCOS. In this large well-phenotyped cohort of women with PCOS, we have studied the prevalence of thyroid dysfunction and hyperprolactinemia compared to controls, and compared this between the four PCOS phenotypes.
METHODS
This retrospective cross-sectional study contains data of 1429 women with PCOS and 299 women without PCOS. Main outcome measures included thyroid stimulating hormone (TSH), Free Thyroxine (FT4), and anti-thyroid peroxidase antibodies (TPOab) levels in serum, the prevalence of thyroid diseases and hyperprolactinemia.
RESULTS
The prevalence of thyroid disease in PCOS women was similar to that of controls (1.9% versus 2.7%; P = 0.39 for hypothyroidism and 0.5% versus 0%; P = 0.99 for hyperthyroidism). TSH levels were also similar (1.55 mIU/L versus 1.48 mIU/L; P = 0.54). FT4 levels were slightly elevated in the PCOS group, although within the normal range (18.1 pmol/L versus 17.7 pmol/L; P < 0.05). The prevalence of positive TPOab was similar in both groups (5.7% versus 8.7%; P = 0.12). The prevalence of hyperprolactinemia was similarly not increased in women with PCOS (1.3%% versus 3%; P = 0.05). In a subanalysis of 235 women with PCOS and 235 age- and BMI-matched controls, we found no differences in thyroid dysfunction or hyperprolactinemia. In according to differences between PCOS phenotypes, only the prevalence of subclinical hypothyroidism was significantly higher in phenotype B (6.3%, n = 6) compared to the other phenotypes.
CONCLUSION
Women with PCOS do not suffer from thyroid dysfunction more often than controls. Also, the prevalence of positive TPOab, being a marker for future risk of thyroid pathology, was similar in both groups. Furthermore, the prevalence of hyperprolactinemia was similar in women with PCOS compared to controls.
Topics: Humans; Female; Polycystic Ovary Syndrome; Hyperprolactinemia; Retrospective Studies; Progesterone; Prevalence; Cross-Sectional Studies; Thyroid Diseases; Hypothyroidism; Thyrotropin
PubMed: 37854182
DOI: 10.3389/fendo.2023.1245106 -
The Journal of Clinical Endocrinology... May 2024Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of PCOS remains indeterminate.
OBJECTIVE
To inform the 2023 international evidence-based guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS.
DATA SOURCES
Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022.
STUDY SELECTION
Thirty trials (n = 2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included.
DATA EXTRACTION
Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes, and adverse effects by 1 reviewer, independently verified by a second.
DATA SYNTHESIS
Thirteen comparisons were assessed, with 3 in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol, but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for body mass indexI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited.
CONCLUSION
The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Inositol; Female; Practice Guidelines as Topic; Insulin Resistance; Evidence-Based Medicine
PubMed: 38163998
DOI: 10.1210/clinem/dgad762 -
Journal of Ethnopharmacology Apr 2024Jiawei Buzhong Yiqi Decoction (JWBZYQ), from records of FuqingzhuNvke, is a classical formula for treating obese women related infertility. JWBZYQ has been shown to be...
ETHNOPHARMACOLOGICAL RELEVANCE
Jiawei Buzhong Yiqi Decoction (JWBZYQ), from records of FuqingzhuNvke, is a classical formula for treating obese women related infertility. JWBZYQ has been shown to be effective in treating polycystic ovary syndrome (PCOS) in both clinical studies and practical practice, with the pharmacological mechanism remaining unknown.
AIM OF THE STUDY
To explore the potential therapeutic effects and mechanistic insights of JWBZYQ in PCOS.
MATERIALS AND METHODS
An overweight PCOS rat model was established via testosterone propionate (TP) injection and 45% high-fat diet (HFD). Then they were categorized into five distinct groups: Control group, Model group, low-dose of JWBZYQ (JWBZYQ1) group, high-dose of JWBZYQ (JWBZYQ2) group, and metformin (Met) group. Body weight, estrous cycle, and sex hormone levels were observed. Hematoxylin-Eosin staining was employed to investigate the histological characteristics of the ovaries. To identify the pathways that changed significantly, transcriptome analysis was performed. The protein and mRNA levels of key molecules in ovarian zona pellucida (ZP) organization, transzonal projections (TZPs) assembly, steroid hormone receptors, and steroidogenesis were assessed using phalloidin staining, immunohistochemistry, Western blot, and polymerase chain reaction.
RESULTS
RNA-seq analysis demonstrated that regulation of hormone secretion, cilium assembly, cell projection assembly, and ZP production may all have crucial impact on the etiology of PCOS and therapeutic effect of JWBZYQ. In particular, PCOS rats exhibited elevated expressions of ZP1-3, which can be reversed by JWBZYQ2 particularly. Simultaneously, TZPs assembly was totally disrupted in PCOS rats, evidenced by the phalloidin staining, upregulated calcium-/calmodulin-dependent protein kinase II beta (CaMKIIβ), and deficient p-CaMKIIβ, myosin X (MYO10), proline-rich tyrosine kinase 2 (PTK2), and Fascin. Nonetheless, JWBZYQ or metformin treatment revived the disturbance, repairing the oocyte-granulosa cell communication, regulating steroidogenesis in PCOS rats. In this way, JWBZYQ and metformin exerted remarkable effects in alleviating altered ovarian morphology and function in PCOS rats, with JWBZYQ2 revealing the best effect.
CONCLUSIONS
JWBZYQ restored the altered ovarian morphology and function by regulating the oocyte-granulosa cell communication, which was related with ZP organization and TZPs assembly in the ovary.
Topics: Humans; Rats; Female; Animals; Polycystic Ovary Syndrome; Phalloidine; Oocytes; Metformin; Cell Communication; Hormones
PubMed: 38158097
DOI: 10.1016/j.jep.2023.117654 -
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