Impact of Sexual Dimorphism on Therapy Response in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: From Conventional and Nutritional Approaches to Emerging Therapies

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of liver disease ranging from hepatic fat accumulation to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma in the absence of excessive alcohol consumption. MASLD is characterized by substantial inter-individual variability in terms of severity and rate of progression, with a prevalence that is generally higher in men than in women. Steroids metabolism is characterized by sexual dimorphism and may have an impact on liver disease progression; indeed, several therapeutic strategies targeting hormone receptors are under phase 2/3 development. Despite the fact that the importance of sexual dimorphism in the setting of MASLD is well recognized, the underlying molecular mechanisms that can potentially drive the disease toward progression are not clear. The aim of this review is to delve into the crosstalk between sexual dimorphism and steroid hormone perturbation under nutritional and pharmacological intervention.