In men with early-stage prostate cancer, staying on a steady dose of hormone‑blocking drugs (continuous ADT) lowered the chance of serious heart problems compared to taking breaks (intermittent ADT), while the risk of diabetes, cholesterol spikes, or bone loss stayed the same.

Intermittent androgen deprivation therapy (iADT) alleviates some side effects of continuous (c) ADT in patients with prostate cancer (PC), but its relative impact on ADT-associated comorbidities is uncertain. We assessed real-world use of iADT and cADT and associated risk of cardiovascular and endocrine/metabolic events in patients with nonmetastatic (nm) PC. This retrospective longitudinal cohort study included patients with nmPC initiating systemic ADT with gonadotropin-releasing hormone agonists (goserelin, histrelin, leuprolide, and triptorelin) or antagonists (degarelix) in the US Surveillance, Epidemiology and End Results-Medicare database (2010-2017), who had ≥ 36 months of continuous insurance coverage, unless death occurred, and did not receive chemotherapy or next-generation hormonal therapies during follow-up (through 2019). Risk of major adverse cardiovascular events (MACE [myocardial infarction, stroke, cardiomyopathy/heart failure, pulmonary embolism, ischemic heart disease, all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, and osteoporosis) were examined between cohorts. Inverse probability of treatment-weighted Cox regression models estimated adjusted hazard ratios (HRs) of the outcomes. Of 10,655 eligible patients, 2,095 (19.7%) received iADT and 8,560 (80.3%) cADT. Median follow-up was 43.9 and 48.4 months and median ADT duration (excluding iADT gaps) was 22.0 and 13.5 months for the iADT and cADT cohorts, respectively. Patients receiving cADT had a lower risk of MACE vs. iADT (HR 0.90; 95% confidence interval [CI] 0.83-0.96). No difference in risk of endocrine/metabolic events was observed (HR 0.97; 95% CI 0.92-1.03). Subgroup analysis found that the difference in MACE was maintained in patients with a history of cardiovascular disease (HR 0.90; 95% CI 0.83-0.98) and eliminated in patients without (HR 0.94; 95% CI 0.82-1.08). Patients with nmPC who received cADT had a lower risk of MACE and similar risk of endocrine/metabolic events vs. those who received iADT. Further research assessing both regimens is needed to inform treatment decisions.