Sexual dimorphism of metabolic dysfunction-associated steatotic liver disease

Trends Mol Med. 2024 Dec;30(12):1126-1136. doi: 10.1016/j.molmed.2024.05.013. Epub 2024 Jun 17.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition. MASLD is a sexually dimorphic condition, with its development and progression influenced by sex chromosomes and hormones. Estrogens typically protect against, whereas androgens promote, MASLD. Therapeutic approaches for a sex-specific personalized medicine include estrogen replacement, androgen blockers, and novel drugs targeting hormonal pathways. However, the interactions between hormonal factors and inherited genetic variation impacts MASLD risk, necessitating more tailored therapies. Understanding sex disparities and the role of estrogens could improve MASLD interventions and management, whereas clinical trials addressing sex differences are crucial for advancing personalized treatment. This review explores the underappreciated impact of sexual dimorphism in MASLD and discusses the potential therapeutic application of sex-related hormones.

Keywords: MASLD; NAFLD; estrogen receptor; fatty liver disease; hormones.

Publication types

  • Review

MeSH terms

  • Androgens / metabolism
  • Animals
  • Estrogens / metabolism
  • Fatty Liver / etiology
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Female
  • Humans
  • Male
  • Metabolic Diseases / genetics
  • Metabolic Diseases / metabolism
  • Sex Characteristics*

Substances

  • Estrogens
  • Androgens