Sex Hormones and the Liver: Implications for Disease Progression and Hormonal Therapy

The liver is central to sex hormone metabolism, and sex hormones in turn modulate hepatic physiology and disease processes. Oestrogens are often protective, while androgens tend to worsen disease progression. The clinical implications of hormonal therapies in patients with liver disease remain an area of active investigation. To review current evidence on the interplay between sex hormones and liver disease, with a focus on the safety and impact of hormonal therapies, including contraception, hormone replacement therapy, assisted reproductive technology and gender-affirming treatments. Prolonged or high-dose oestrogen exposure, particularly via oral contraceptives, has been associated with intrahepatic cholestasis and hepatocellular adenoma (HCA), especially in predisposed individuals. In contrast, hormone replacement therapy in postmenopausal women is generally safe and may confer metabolic and hepatic benefits. Oestrogens appear to slow fibrosis progression and reduce hepatocellular carcinoma risk, whereas androgens can promote steatosis and HBV-related oncogenesis. Hormonal therapies are safe in most patients with compensated chronic liver disease but require caution in settings such as in polycystic liver disease, where oestrogens can accelerate cyst growth. Emerging data also indicate a role of sex hormones in autoimmune and cholestatic diseases, as well as in outcomes of assisted reproduction and gender-affirming therapy. Hormonal therapies are feasible in most liver disease contexts, but individualised assessment, awareness of genetic predisposition, and disease-specific risks are essential to optimise safety and therapeutic benefit.