Current aspects of the role of insulin resistance, systemic inflammation, and oxidative stress in the pathogenesis of hyperandrogenism and abnormal folliculogenesis in patients with polycystic ovary syndrome

DOI

https://dx.doi.org/10.18565/aig.2021.5.55-63

Belova I.S., Khashchenko E.P., Uvarova E.V.
Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia

Polycystic ovary syndrome (PCOS) is a pathological symptom complex characterized by oligo-anovulation, hyperandrogenism and impaired ovarian structure and function. PCOS occurs in 8–13% of early reproductive-age patients. Despite numerous studies, there is no common understanding of the causes of PCOS. In the pathogenesis of the disease, special attention is paid to concurrent hormonal disorders in the presence of metabolic ones. The manifestation of the metabolic syndrome is noted in an average of 20% of patients with PCOS by the age of 20 years and in 35–50% by the age of 30 years; the vast majority (35–90%) of them are recorded to have insulin resistance (IR). At the same time, 38–88% of patients with PCOS are overweight. Studying the signaling pathways involved in the development of the symptom complex has established a relationship between the vicious circle of IR and hyperandrogenism. This literature review places a special emphasis on impaired intracellular insulin signaling in the pathogenesis of PCOS. There is an update on fast and very fast PI3K/AKT pathways, slow and very slow MAPK and mTOR pathways of intracellular insulin signaling, which affect the processes of glycolysis and glucogenesis, lipolysis and lipogenesis, systemic inflammation and oxidative stress, proliferation and apoptosis, which occurs in the development of PCOS. The paper presents available data on the mechanisms of impact of mitochondrial dysfunction and oxidative stress on IR aggravation, hyperandrogenism, and abnormal folliculogenesis in PCOS. It considers the role of activation of the nuclear factor NF-kB signaling pathway in inflammation and synthesis of proinflammatory cytokines in conjunction with the accumulation of glycation end products and reactive oxygen species in changing steroidogenesis and increasing hyperandrogenism in PCOS.
Conclusion. Thus, the review summarizes the update on the insulin signaling pathways involved in the development of PCOS, which confirm the mutual aggravation and progression of IR and hyperandrogenism.

polycystic ovary syndrome

insulin resistance

hyperandrogenism

systemic inflammation

intracellular signaling

insulin

oxidative stress

gluconeogenesis

lipolysis

kisspeptin

Full text (in Russian)

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Received 13.10.2020

Accepted 15.02.2021

Irina S. Belova, medical resident, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. E-mail: irsenb@inbox.ru. 117997, Russia, Moscow, Ac. Oparina str., 4.
Elena P. Khashchenko, senior researcher at the Department of Pediatric Gynecology, Academician V.I. Kulakov National Medical Research Center for Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. E-mail: khashchenko_elena@mail.ru. 117997, Russia, Moscow, Ac. Oparina str., 4.
Elena V. Uvarova, MD, PhD, Professor, Head of the Department of Pediatric Gynecology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. E-mail: elena-uvarova@yandex.ru. 117997, Russia, Moscow, Ac. Oparina str., 4.

For citation: Belova I.S., Khashchenko E.P., Uvarova E.V. Current aspects of the role of insulin resistance, systemic inflammation, and oxidative stress in the pathogenesis of hyperandrogenism and abnormal folliculogenesis in patients with polycystic ovary syndrome.
Akusherstvo i Ginekologiya/ Obstetrics and gynecology. 2021; 5: 55-63 (in Russian)
https://dx.doi.org/10.18565/aig.2021.5.55-63

Current aspects of the role of insulin resistance, systemic inflammation, and oxidative stress in the pathogenesis of hyperandrogenism and abnormal folliculogenesis in patients with polycystic ovary syndrome

Belova I.S., Khashchenko E.P., Uvarova E.V.

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