Unravelling sex-specific differences in autosomal dominant polycystic kidney disease: a multiorgan perspective.

Autosomal dominant polycystic kidney disease (ADPKD) is a complex, multisystemic disorder exhibiting notable sex-related differences in clinical presentation, progression and complications. While the disease affects both sexes, disease expression and complications differ significantly between men and women. This review explores the biological, hormonal and psychosocial sex differences in ADPKD across multiple clinical domains. Men tend to experience faster kidney growth, earlier onset of hypertension and slightly younger age at kidney replacement therapy. Women, in contrast, are more susceptible to polycystic liver disease (PLD), often exacerbated by oestrogen exposure, especially during pregnancy or hormonal treatments. Although urinary tract infections are more prevalent among women, cyst infections show no major sex-based difference in incidence, although men may respond less favourably to antibiotic therapy. Cardiovascular complications, intracranial aneurysms and reproductive health risks also show sex-related patterns. Fertility and reproductive counselling must be individualized, as reproductive challenges and risks differ markedly between men and women. Pregnancy in women with ADPKD, especially those with reduced renal function or PLD, carries increased risks and requires specialized care. Fertility in men with ADPKD is usually preserved, although sometimes it may be impaired due to seminal vesicle cysts and sperm morphological abnormalities. However, assisted reproductive techniques generally achieve outcomes comparable to those of unaffected individuals. Psychosocial aspects such as pain, emotional burden and quality of life are also influenced by sex and require integrated management strategies. While tolvaptan slows disease progression in both sexes, pharmacodynamic responses may differ slightly. Incorporating sex-specific insights into ADPKD care, including hormonal and reproductive considerations, is critical to advancing personalized medicine. Understanding these differences will optimize management and improve quality of life for individuals living with ADPKD.