Abstracts Womens Studies

Circuitos neuronais envolvidos na etiologia da síndrome dos ovários policísticos e seus desfechos emocionais: uma revisão sistemática

by Josiane Barcelos Dutra

Abstract: Polycystic Ovary Syndrome (PCOS) is a multifactorial neuroendocrine disorder that causes damage to women's reproductive, metabolic and emotional health, but its etiology is still controversial. Epigenetic, metabolic factors and more recently, disturbances in the neuronal circuits that regulate the hypothalamic-pituitary-ovarian (HHO) axis, are considered the main triggers for the symptoms of PCOS. Since little is known about the installation of emotional disturbances in the syndrome, the purpose of this review (PROSPERO; ID CRD42022296183) was to determine evidence in the literature (2010-2021) that supports the role of different neurotransmitter systems in the etiology of PCOS and associated emotional disorders. This study hypothesizes that changes in these neuronal circuits contribute not only to the pathogenesis of the syndrome but also to the installation of symptoms of depression and anxiety in women with PCOS. This systematic review followed the PRISMA Statement guidelines, searching for scientific publications in any language in two databases (Pubmed and Web Of Science). In the group of 71 articles selected in this review, 72% were related to general mechanisms regulating the HHO axis. Also, 28% were carried out with animal models of PCOS induced by different interventions. Androgenized animals (50%) at different stages like prenatal (50%), neonatal (17%), prepubertal (25%) and adult (8%) presented different results in the concentrations of luteinizing hormone (LH), kisspeptin mRNA expression and changes (increase and decrease) in neurotransmitter signaling such as noradrenaline (NA), dopamine (DA) and serotonin (5-HT). In 17% of the studies, PCOS induced by letrozole in the prepubertal phase led to a reduction in the neurotransmitters 5-HT, NA and gamma-aminobutyric acid (GABA). However, 13% of the studies used estradiol valerate (VE) in the neonatal (67%) and adult (33%) phases and found an increase in 5-HT, NA and glutamate, with a reduction in GABA levels. Induction of PCOS by stress with light exposure (8%), progesterone blocker (RU486) (4%), dehydroepiandrosterone (DHEA) (4%) and estrogen receptor a knockout animals (ERaKO) (4%) also presented dissonant results among the analyzed parameters. In summary, animal models of PCOS show high variation in their results according to the type of intervention, duration and life stage of PCOS induction. As expected, of the total number of publications inserted, only 4% related central neuronal alterations of PCOS with psychological disorders. Despite the lack of consensus and the need for further studies, this review suggests possible associations of the reduction of neurotransmitters like 5-HT, NA, GABA and RFamide-related peptide-3 (RFRP-3), as key factors for understanding the installation of the psychological dysfunctions of PCOS. In this way, we hope to contribute to the understanding of the etiology of PCOS and to the search for new treatments that can combine the improvement of reproductive and emotional symptoms, in the integral care of women's…