Androgen-targeting therapeutics mitigate the adverse effect of GnRH agonist on the risk of neurodegenerative disease in men treated for prostate cancer

A retrospective cohort analysis of roughly 1.8 million men with prostate cancer in a US claims database (about 210,000 meeting inclusion criteria, ~6.4 years mean follow-up) examined how different classes of androgen-targeting drugs related to neurodegenerative disease risk. GnRH agonist monotherapy was linked to a substantially elevated risk of any neurodegenerative disease (relative risk about 1.47), while co-treatment with abiraterone lowered the Alzheimer's and Parkinson's risk conferred by GnRH agonists, and androgen receptor inhibitors reduced ALS risk. The authors propose that GnRH analogs cross the blood–brain barrier and disturb stage-specific GnRH/LH signaling in the brain, making the GnRH-axis disruption itself — not just low testosterone — a driver of neurological risk.