Autoantibodies Targeting the Hypothalamic-Pituitary-Ovarian Axis in Polycystic Ovary Syndrome: Emerging Key Players in Pathogenesis?

Polycystic ovary syndrome (PCOS) is a common female endocrinopathy associated with reproductive and metabolic abnormalities. PCOS is characterized by complex pathogenesis and pathophysiology. Its multifactorial etiology and heterogeneous presentation make effective treatment difficult. Endocrine abnormalities in PCOS create a vicious cycle of overriding dysfunction involving the hypothalamic-pituitary-ovarian (HPO) axis. Most research has primarily focused on identifying genetic, epigenetic, or immunological factors underlying PCOS. In recent years, new reports have emerged on the possible involvement of antibodies directed against HPO axis components in the development of PCOS. Some of these have been shown to be able to interfere with hormone receptors or receptor binding by targeting the key domains for their function. However, the evidence is heterogeneous and challenging to interpret, given the overall predisposition to high levels of various autoantibodies found in women with PCOS. This review focuses on autoantibodies affecting the HPO axis in PCOS and their potential role in the pathogenesis of PCOS. The authors discuss PCOS as a potential antibody-mediated autoimmune disease in light of recent reports on its possible pathogenesis.