The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age that encompasses a multitude of signs and symptoms, including hyperandrogenism, polycystic ovarian morphology, ovulatory dysfunction, and insulin resistance. The study aims to explore the role of aromatic amino acid (AAA) disorders in the syndrome. A systematic search on the databases Scopus, PubMed, and Google Scholar until 20 July 2024 over the past 5 years regarding metabolomic studies on PCOS patients' blood and the status of AAAs resulted in 12 related papers. Our review showed that AAA metabolic pathways are dysregulated, and their levels in the blood serum and plasma of PCOS patients in most studies are elevated due to inflammation and oxidative stress which, assisted by gut dysbiosis, give rise to insulin resistance that develops into PCOS. AAA abnormalities can also directly induce the defining symptoms of the syndrome through diminished neurotransmitter availability and impaired signaling. According to our review, AAA perturbations are detected in every stage of PCOS pathophysiology, making them valuable biomarkers for early diagnosis and management of the syndrome. Further investigation of the biological function, role, and impact of AAAs, probably alongside other metabolites, including BCAAs, could lead to the discovery of new tools for preventing and managing PCOS symptoms.

Keywords: Aromatic Amino Acids; Inflammation; Insulin Resistance; Metabolomics; Phenylalanine; Polycystic Ovary Syndrome; Tryptophan; Tyrosine.

Figure 1

PRISMA flowchart detailing the search process.

Figure 2

Graphical summary of the main characteristics of the bibliographic search on modified aromatic amino acid levels in the blood of polycystic ovary syndrome (PCOS) sufferers. A systematic review on PCOS was conducted. The studied samples were serum and plasma analyzed by liquid chromatography–mass spectrometry (LC-MS), gas chromatography–mass spectrometry (GC-MS), and proton-nuclear magnetic resonance spectroscopy (¹H NMR). Prominent phenotypes were obesity, insulin resistance, hyperandrogenism, metabolic syndrome, and B-type PCOS although in some studies there was not a specific phenotype examined. The vast majority of studies reported increased levels of aromatic amino acids in PCOS patients.

Figure 3

Inflammation and oxidative stress form a feedback loop, inducing the onset of insulin resistance. Insulin resistance is considered a precursor of polycystic ovary syndrome (PCOS). Once PCOS is established, apart from the diagnostic criteria, hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, it may encompass a multitude of symptoms such as hirsutism, acne, alopecia, metabolic dysfunction, and mood disorders. Aromatic amino acid (AAAs) metabolism perturbations have been reported in PCOS but also mark inflammation, oxidative stress, and insulin resistance.

Figure 4

Suggested biochemical pathways of AAAs’ influence on PCOS. Phe: phenylalanine, Trp: tryptophan, IRs: insulin receptors, Tyr-P: tyrosine phosphorylation, IRS-1: insulin receptor substrate-1, GnRH: gonadotropin-releasing hormone, LH: luteinizing hormone, PCOS: polycystic ovary syndrome, AAAs: aromatic amino acids, BCAAs: branched-chain amino acids, GCH1:GTP-cyclohydrolase 1, IDO: indoleamine-2,3-dioxygenase, IFN-γ: interferon-γ, BAs: bile acids, IL-22: interleukin-22, AhR: aryl hydrocarbon receptor.