Metabolic and inflammatory marker elevations and associations with hormone therapy usage in prostate cancer patients of the All of Us Research Program cohort.

5031 Background: The development of cardiovascular disease (CVD) involves an interplay of inflammatory and metabolic factors. While hormone therapy (HT) is associated with increased CVD risk in prostate cancer (PCa) patients, the underlying mechanism remains unclear. Prior studies suggest an association between hypogonadism and systemic inflammation, but the specific effect of HT is poorly understood. Utilizing the All of Us Research Program, we investigated the effects of HT on metabolic and inflammatory markers. Methods: Our study examined All of Us participants who were diagnosed with PCa and were either treated or not treated with HT (GnRH agonists, GnRH antagonists, and/or anti-androgens), as well as those who received HT for non-PCa indications. We used ANCOVA to evaluate the effect of HT on metabolic and inflammatory labs after adjusting for pre-PCa baseline values. Among HT-treated PCa patients without prior CVD (myocardial infarction, stroke, or heart failure), we used Gray's test to compare CVD time-to-event between participants with and without elevated inflammatory labs (CRP > 10, ESR > 20, or Ferritin > 300) after HT treatment. In the non-PCa cohort, paired T-tests compared pre-HT and post-HT values. Results: The study included 7124 participants with PCa (1480 with HT; 5644 controls) and 2683 participants without PCa who received HT. After adjustment for baseline values, HT usage was associated with increased HgbA1c (P<0.001), HDL (P<0.001), triglycerides (P<0.001), ESR (P=0.006), CRP (P=0.009), and ferritin (P=0.006). Similar trends were seen in the non-PCa cohort (Table). In our survival analysis, HT-treated PCa patients with elevated inflammatory labs had higher CVD risk (P<0.001). Conclusions: Our study demonstrated associations between HT usage and metabolic dysregulation, while also suggesting a pro-inflammatory effect of HT in PCa patients. These trends reinforce prior studies and were similar among those without PCa, suggesting a drug-class effect. Our study also observed an increased risk of CVD among HT-treated PCa patients with elevated inflammatory labs. Future research should explore the role of HT associated inflammation in CVD, as well as identify targets for risk mitigation. Lab HT Treatment EMM (SE) No HT TreatmentEMM (SE) P-value(ANCOVA) Non-PCa Pre-HTMean Non-PCa Post-HTMean P-Value (Paired T-test) HgbA1c (%) 6.34 (0.04) 6.15 (0.02) P< 0.001 5.8 6.0 P<0.001 LDL (mg/dL) 102 (1.10) 101 (0.55) P= 0.71 103.0 107.6 P<0.001 HDL (mg/dL) 52.0 (0.17) 49.7 (0.33) P< 0.001 55.0 55.9 P= 0.02 Triglycerides (mg/dL) 136 (2.33) 127 (1.18) P< 0.001 117.5 124.1 P= 0.001 CRP (mg/L) 45.7 (8.81) 24.9 (4.61) P= 0.009 19.8 23.3 P= 0.45 ESR (mm/hr) 28.0 (2.27) 21.8 (1.19) P= 0.006 27.1 30.2 P= 0.02 Ferritin (ng/mL) 303 (55.8) 267 (34.2) P= 0.006 195.7 338.6 P= 0.02 EMM= Estimated Marginal Mean, SE = Standard Error.