The Ovary-Liver Axis: Molecular Science and Epidemiology

In women, gonadal hormones play a crucial regulatory role in body fat distribution and glucose-lipidic homeostasis, which are closely associated with the hepatic steatogenesis and intrahepatic inflammatory pathways. Accumulating evidence supports the idea that hepatic health is closely linked to endocrine ovarian function through hormonal, metabolic, and immunological communications, collectively known as the "ovary-liver axis". This review presents the molecular mechanisms involved in sex hormone synthesis, metabolism, and signaling pathways along the ovary-liver axis, focusing on dysregulated mechanisms that may contribute to common disorders and, specifically to hepatic derangements in the context of altered ovarian function. Additionally, we analyzed epidemiological evidence supporting the ovary-liver axis, specifically examining meta-analytic studies exploring the connection between polycystic ovary syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). We also discuss studies linking hypogonadism with liver health, with a specific focus on Turner syndrome and MASLD. Furthermore, we explore the impact of menopause on liver health. Our integrated molecular and epidemiological approach identifies important clinical and public health implications, aiming to uncover potentially innovative interventions and effective strategies for managing disease progression. However, unexplored areas within the ovary-liver axis highlight the need for further research on causal pathways.