A large retrospective study published in JAMA Oncology reveals that men with prostate cancer who receive combined androgen deprivation therapy (ADT) and androgen receptor pathway inhibitor (ARPI) therapy face a significant and rapidly accumulating risk of metabolic syndrome (MetS). Drawing on data from over 16,900 patients across more than 1,800 U.S. hospitals, researchers found that MetS incidence climbed steadily throughout the entire first year of treatment.

Older patients bore a disproportionate burden — men aged 70–79 had the highest event rate and were significantly more likely to develop dyslipidemia, insulin resistance, hypertension, and MetS compared to younger patients. Hypertension emerged as the most common metabolic complication, while obesity risk appeared to decline with age. Exploratory findings also hinted at differences in metabolic outcomes depending on which ARPI was used.

By the Numbers:

• 39.1% — overall cumulative incidence of MetS at 12 months
• 204.9 events per 1,000 person-months — incidence of hypertension, the most common metabolic abnormality
• 245.5 events per 1,000 person-months — overall incidence of any metabolic dysfunction
• Men aged 70–79 had 51.7 MetS events per 1,000 person-months, the highest of any age group

Why it matters: As ADT-ARPI combinations become increasingly standard in prostate cancer care, clinicians need to proactively monitor and manage metabolic health — especially in older patients — to reduce the long-term cardiovascular and metabolic risks associated with these therapies.