scholarly journals Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuang Li ◽  
Linhai Zhang ◽  
Nian Wei ◽  
Zhenzhen Tai ◽  
Changyin Yu ◽  
...  

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sairish Ashraf ◽  
Shayaq Ul Abeer Rasool ◽  
Mudasar Nabi ◽  
Mohd Ashraf Ganie ◽  
Shariq R. Masoodi ◽  
...  

AbstractPolycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in pre-menopausal women having complex pathophysiology. Several candidate genes have been shown to have association with PCOS. CYP19 gene encodes a key steroidogenic enzyme involved in conversion of androgens into estrogens. Previous studies have reported contradictory results with regard to association of SNP rs2414096 in CYP19 gene with PCOS and hyperandrogenism in different ethnic populations. Present study was aimed to investigate the impact of SNP rs2414096 polymorphism of CYP19 gene on susceptibility of PCOS and hyperandrogenism in Kashmiri women. Further we also studied the genotypic-phenotypic association for various clinical and biochemical parameters of this polymorphism. Case control study. 394 PCOS cases diagnosed on the basis of Rotterdam criteria and age matched 306 healthy women. We found a significant differences in genotypic frequency (χ2 = 18.91, p < 0.05) as well as allele frequency (OR 0.63, CI 0.51–0.78, χ2 = 17.66, p < 0.05) between PCOS women and controls. The genotype–phenotype correlation analysis showed a significant difference in FG score (p = 0.047) and alopecia (p = 0.045) between the three genotypes. Also, the androgen excess markers like DHEAS (p < 0.001), Androstenedione (p < 0.001), Testosterone (p < 0.001) and FAI (p = 0.005) were significantly elevated in GG genotype and showed a significant difference in additive model in PCOS women. rs2414096 polymorphism of CYP19 gene is associated with the risk of PCOS as well as with clinical and biochemical markers of hyperandrogenism, hence suggesting its role in clinical manifestations of PCOS in Kashmiri women.


Author(s):  
Sisi Yan ◽  
Jinli Ding ◽  
Yi Zhang ◽  
Jiayu Wang ◽  
Sainan Zhang ◽  
...  

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.


Author(s):  
Somnath Singh Raghuvanshi ◽  
Anirban Sinha ◽  
Animesh Maiti ◽  
Partha Pratim Chakraborty ◽  
Asish Kumar Basu ◽  
...  

Background: Ovarian steroidogenesis requires gonadotropin stimulation, Luteinizing Hormone (LH) is a key factor in the hyperandrogenaemia of the polycystic ovary syndrome. Progesterone is the primary regulator of Gonadotropin-Releasing Hormone (GnRH) pulse frequency; however, in the polycystic ovary syndrome, the GnRH pulse generator is relatively resistant to the negative feedback effects of progesterone.  Study aims to evaluate the association of Anti-mullerian hormone with serum androgen and gonadotropin level in adolescents and young women of Polycystic Ovary Syndrome (PCOS).Methods: This was a single centre observational Cross-sectional study carried out in the department of Endocrinology and metabolism, Medical College, Kolkata from March 2017 to January 2019. Total number of study subjects were 207 out of which 138 were cases.Results: The AMH had strong positive correlation with serum testosterone in both case and control groups (r 0.542, p<0.001 and r 0.57, p<0.001) respectively .After the adjustment of age and BMI , the AMH moderately positive  but extremely significant correlation with serum testosterone as compare to control.Conclusions: Hyperandrogenaemia and higher ratio of LH and FSH associated with higher serum AMH level is associated with the higher serum AMH in polycystic ovarian syndrome.


2021 ◽  
Author(s):  
Xiaoxuan Zhao ◽  
Xiaoling Feng ◽  
Xinjie Zhao ◽  
Yuepeng Jiang ◽  
Xianna Li ◽  
...  

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder,with an increased risk of type 2 diabetes mellitus and cardiovascular disease, of which metabolic syndrome (MS) is an indispensable springboard to communicate PCOS and various comlications. Our aim was to study the potential metabolic characteristics of PCOS-MS, and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis and treatment.Methods: 44 PCOS patients with MS, 34 PCOS patients without MS and 32 healthy controls were studied. Plasma samples of subjects were tested by ultra performance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators.Results: There were significant difference in general characteristics, reproductive hormone and metabolic parameters in PCOS-MS group when compared with PCOS group and healthy controls. We found 30 differential metabolites which were involved in 23 pathways when compared with PCOS group. The metabolic network further reflects the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions and metabolites.In the correlation analysis, 17 pairs of correlation coefficient between differential metabolites and clincal parameters were greater than 0.4, involving 11 metabolites that has the potential to be a marker for clinical diagnosis. They were assessed by ROC whose area under curve (AUC) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid+leucine+phenylalanine and carnitine C 4: 0+carnitine C18:1+carnitine C5:0 are expected to be sensitive combinational biomarkers in clinical practice.Conclusion: Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.


2019 ◽  
Vol 7 (8) ◽  
pp. 84 ◽  
Author(s):  
Coutinho ◽  
Kauffman

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, affecting at least 10% of women of reproductive age. PCOS is typically characterized by the presence of at least two of the three cardinal features of hyperandrogenemia (high circulating androgen levels), oligo- or anovulation, and cystic ovaries. Hyperandrogenemia increases the severity of the condition and is driven by increased luteinizing hormone (LH) pulse secretion from the pituitary. Indeed, PCOS women display both elevated mean LH levels, as well as an elevated frequency of LH pulsatile secretion. The abnormally high LH pulse frequency, reflective of a hyperactive gonadotropin-releasing hormone (GnRH) neural circuit, suggests a neuroendocrine basis to either the etiology or phenotype of PCOS. Several studies in preclinical animal models of PCOS have demonstrated alterations in GnRH neurons and their upstream afferent neuronal circuits. Some rodent PCOS models have demonstrated an increase in GnRH neuron activity that correlates with an increase in stimulatory GABAergic innervation and postsynaptic currents onto GnRH neurons. Additional studies have identified robust increases in hypothalamic levels of kisspeptin, another potent stimulator of GnRH neurons. This review outlines the different brain and neuroendocrine changes in the reproductive axis observed in PCOS animal models, discusses how they might contribute to either the etiology or adult phenotype of PCOS, and considers parallel findings in PCOS women.


2020 ◽  
Vol 29 (17) ◽  
pp. 2813-2830
Author(s):  
Ville Veikkolainen ◽  
Nsrein Ali ◽  
Milena Doroszko ◽  
Antti Kiviniemi ◽  
Ilkka Miinalainen ◽  
...  

Abstract Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders leading to infertility in women affecting reproductive, endocrine and metabolic systems. Recent genomewide association studies on PCOS cohorts revealed a single nucleotide polymorphism (SNP) in the ERBB4 receptor tyrosine kinase 4 gene, but its role in ovary development or during folliculogenesis remains poorly understood. Since no genetic animal models mimicking all PCOS reproductive features are available, we conditionally deleted Erbb4 in murine granulosa cells (GCs) under the control of Amh promoter. While we have demonstrated that Erbb4 deletion displayed aberrant ovarian function by affecting the reproductive function (asynchronous oestrous cycle leading to few ovulations and subfertility) and metabolic function (obesity), their ovaries also present severe structural and functional abnormalities (impaired oocyte development). Hormone analysis revealed an up-regulation of serum luteinizing hormone, hyperandrogenism, increased production of ovarian and circulating anti-Müllerian hormone. Our data implicate that Erbb4 deletion in GCs leads to defective intercellular junctions between the GCs and oocytes, causing changes in the expression of genes regulating the local microenvironment of the follicles. In vitro culture assays reducing the level of Erbb4 via shRNAs confirm that Erbb4 is essential for regulating Amh level. In conclusion, our results indicate a functional role for Erbb4 in the ovary, especially during folliculogenesis and its reduced expression plays an important role in reproductive pathophysiology, such as PCOS development.


2019 ◽  
Vol 78 ◽  
pp. 01009
Author(s):  
Yanan Yin ◽  
Weiwei Yang ◽  
Yingliang Jiao ◽  
He Yang ◽  
Xinglin Li

Diabetes is an endocrine system disease characterized by high morbidity, high prevalence, and high mortality. Although the traditional medicine for treating diabetes has a good effect, its side effects are also large. Traditional Chinese medicine has also achieved good therapeutic effects in the treatment of diabetes, and the side effects of Chinese medicine are small. Coix is a medicinal and edible plant. It is used as food and medicine alone or in combination with other herbs in the early days. Its seeds have become one of the most popular Chinese herbal medicines. The coixan was extracted from Coix seed, and it was administered to diabetic mice. After five weeks of treatment, it was found to have some role in hypoglycemic. This study provides a good application prospect for Chinese medicine treatment of diabetes.


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