多囊卵巢综合征(PCOS)是最常见的内分泌疾病,影响5-20%的育龄妇女。然而,PCOS的治疗主要基于症状而不是病理生理学。神经内分泌紊乱,如PCOS患者LH/FSH比值升高所示,被认为是综合症的核心机制,尤其是瘦PCOS。LH和FSH的分泌受下丘脑GnRH神经元的GnRH搏动性的影响。Kisspeptin是GnRH分泌的主要调节因子,而神经激肽B(NKB)和强啡肽调节KNDy神经元中的kisspeptin分泌。本研究旨在加深对瘦PCOS患者神经内分泌紊乱及其潜在病理生理基础治疗的认识。在CiptoMangunkusumoKencana博士医院和IMERIUIHRIFP集群进行了一项横断面研究,以110名瘦PCOS患者为受试者。LH,FSH,LH/FSH比值,kisspeptin,NKB,强啡肽,瘦素,脂联素,AMH,空腹血糖,空腹胰岛素,HOMA-IR,睾丸激素,测量SHBG。进行双变量和路径分析以确定变量之间的关系。强啡肽和kisspeptin之间有负相关,而NKB水平与kisspeptin无关。kisspeptin与LH/FSH比值之间没有直接关联;有趣的是,在双变量和通路分析中,强啡肽与LH/FSH比值呈正相关。在两项分析中,AMH与LH/FSH比值呈正相关。路径分析显示,瘦型PCOS患者强啡肽和kisspeptin水平之间存在关联,而NKB与kisspeptin无关。此外,AMH与LH/FSH比值之间存在相关性,但kisspeptin水平与LH/FSH比值没有直接显著关系。HOMA-IR与脂联素水平呈负相关,与瘦素和FAI水平呈正相关。总之,AMH与FAI水平呈正相关,与LH/FSH比值直接相关,显示其在瘦PCOS神经内分泌学中的重要作用。从路径分析来看,AMH也是HOMA-IR和FAI与LH/FSH比值之间的中介变量。有趣的是,这项研究发现强啡肽与LH/FSH比值之间存在直接正相关,而kisspeptin与LH/FSH比值之间没有相关性。需要进一步的研究来研究AMH和强啡肽作为瘦PCOS患者管理的潜在治疗目标。
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-20% of reproductive-age women. However, the treatment of PCOS is mainly based on symptoms and not on its pathophysiology. Neuroendocrine disturbance, as shown by an elevated LH/FSH ratio in PCOS patients, was thought to be the central mechanism of the syndrome, especially in lean PCOS. LH and FSH secretion are influenced by GnRH pulsatility of GnRH neurons in the hypothalamus. Kisspeptin is the main regulator of GnRH secretion, whereas neurokinin B (NKB) and
dynorphin regulate kisspeptin secretion in KNDy neurons. This study aims to deepen the understanding of the neuroendocrine disorder in lean PCOS patients and its potential pathophysiology-based therapy. A cross-sectional study was performed at Dr. Cipto Mangunkusumo Kencana Hospital and the IMERI UI HRIFP cluster with 110 lean PCOS patients as subjects. LH, FSH, LH/FSH ratio, kisspeptin, NKB, dynorphin, leptin, adiponectin, AMH, fasting blood glucose, fasting insulin, HOMA-IR, testosterone, and SHBG were measured. Bivariate and path analyses were performed to determine the relationship between variables. There was a negative association between
dynorphin and kisspeptin, while NKB levels were not associated with kisspeptin. There was no direct association between kisspeptin and the LH/FSH ratio; interestingly,
dynorphin was positively associated with the LH/FSH ratio in both bivariate and pathway analyses. AMH was positively correlated with the LH/FSH ratio in both analyses. Path analysis showed an association between
dynorphin and kisspeptin levels in lean PCOS, while NKB was not correlated with kisspeptin. Furthermore, there was a correlation between AMH and the LH/FSH ratio, but kisspeptin levels did not show a direct significant relationship with the LH/FSH ratio. HOMA-IR was negatively associated with adiponectin levels and positively associated with leptin and FAI levels. In conclusion, AMH positively correlates with FAI levels and is directly associated with the LH/FSH ratio, showing its important role in neuroendocrinology in lean PCOS. From the path analysis, AMH was also an intermediary variable between HOMA-IR and FAI with the LH/FSH ratio. Interestingly, this study found a direct positive correlation between
dynorphin and the LH/FSH ratio, while no association between kisspeptin and the LH/FSH ratio was found. Further research is needed to investigate AMH and dynorphin as potential therapeutic targets in the management of lean PCOS patients.