Polycystic ovarian syndrome: signs and feedback effects of hyperandrogenism and insulin resistance

Abstract

Polycystic ovary syndrome (PCOS) is a disease whose diagnosis is based on the detection of hyperandrogenism (HA) and ovulatory dysfunction. Women with PCOS frequently develop insulin resistance (IR), which generates a metabolic condition that involves a decrease in the action of insulin at the cellular level and is linked to compensatory hyperinsulinemia (HI). In PCOS, the ovary remains sensitive to the action of insulin. Additionally, it has been observed that the main effect of insulin in the ovary is the stimulation of androgen synthesis, resulting in HA, one of the fundamental characteristics of the PCOS. In this sense, the excess of androgens favors the development of IR, thus perpetuating the cycle of IR-HI-HA, and therefore PCOS. Moreover, mitochondrial dysfunction is present in PCOS patients and is a common feature in both IR and HA. This review places electron transfer as a key element in HA and IR development, with emphasis on the relationship between androgen biosynthesis and mitochondrial function. Indeed, metformin has been involved in repair mitochondrial dysfunction, decrease of oxidative stress, reduction of androgens levels and the enhancing of insulin sensitivity. Therefore, we propose that treatment with metformin could decrease HI and consequently HA, restoring, at least in part, the metabolic and hormonal disorders of PCOS.

多囊卵巢综合征：高雄激素血症和胰岛素抵抗的体征及反馈效应 摘要

多囊卵巢综合征（PCOS）是一种以高雄激素血症（HA）和排卵功能障碍为诊断基础的疾病。患有多囊卵巢综合征的女性经常出现胰岛素抵抗（IR）, 这种代谢状况包括细胞对胰岛素反应的降低, 并与代偿性高胰岛素血症（HI）有关。在PCOS中, 卵巢对胰岛素仍然敏感。此外, 胰岛素在卵巢中的主要作用是刺激雄激素合成, 造成HA, 这是PCOS的基本特征之一。从这个意义上说, 过量的雄激素青睐于IR的进展, 从而使IR-HI-HA循环持续, 造成PCOS。此外, 线粒体功能障碍也存在于PCOS患者中, 是IR和HA的共同特征。本综述以电子转移为HA和IR进展的关键因素, 重点介绍了雄激素生物合成与线粒体功能间的关系。事实上, 二甲双胍参与修复线粒体功能障碍、降低氧化应激、降低雄激素水平并提高胰岛素敏感性。因此, 我们认为二甲双胍治疗可以降低HI, 进而降低HA, 至少在一定程度上纠正PCOS的代谢与激素的紊乱。

Keywords:

• Steroidogenesis
• androgens
• hyperinsulinemia
• mitochondrial dysfunction
• NADPH

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT/DGAPA/UNAM) under Grant IA211020.