Are higher follicle-stimulating hormone levels before androgen deprivation therapy for prostate cancer associated with oncological and cardiac outcomes and overall survival? —a population-level analysis

Background: Androgen deprivation therapy (ADT), commonly delivered via a luteinizing hormone-releasing hormone (LHRH) agonist, is the standard treatment for advanced prostate cancer (PC). While quite effective, it has been associated with an increased risk of major adverse cardiovascular events (MACE). The exact mechanisms are not clear. However, it has been theorized that follicle-stimulating hormone (FSH), a pituitary hormone that is involved in controlling normal testosterone levels, which is decreased with LHRH-agonist therapy, may be the culprit. We performed a retrospective population-level study to test the link of FSH levels on the development of MACE, castrate-resistant PC (CRPC), and death among men starting ADT. Methods: All men (n=1,539) who had an FSH level between 1999 and 2018 within 2 years prior to starting ADT and complete data were identified within the Veterans Affairs (VA) Health System. FSH was dichotomized as low/normal (≤8 IU/mL) and high (>8 IU/mL), using established cut-points. The associations between FSH and time to MACE, death, and CRPC were tested using log-rank tests and multivariable Cox proportional hazards models. Results: Patients with high FSH were older (median 76 vs. 73 years, P<0.001), started ADT earlier (median 2007 vs. 2009, P=0.027), and had lower body mass index (BMI) (median 29.1 vs. 30.1 kg/m², P=0.004) compared to those with low/normal FSH. On multivariable analysis, there was no association between FSH and time from ADT to MACE, CRPC, or death. Conclusions: In this population-level study of men receiving an FSH test prior to starting ADT, there was no association between FSH levels and time from ADT to MACE, CRPC, or death. Although further studies are needed, these results do not support a link between pre-ADT FSH and long-term oncological or cardiovascular outcomes.