Divergent Effects of Gonadotropin-releasing Hormone (GnRH) Agonist and GnRH Antagonist Treatment on Platelet Activity and Transcriptome
Authors' conclusion
Prostate cancer is associated with heightened platelet activation and thromboinflammatory signaling. Treatment with leuprolide, but not relugolix, was associated with further augmented platelet activity.
Study context
- Population
- Patients with prostate cancer initiating first-line androgen deprivation therapy (ADT)
- Participants
- 69 patients
- Exposure
- Relugolix vs leuprolide
- Leuproliden = 40
- Relugolixn = 29
- Outcome
- Platelet activation by flow cytometry (P-selectin, PAC-1, CD40, CD40L, monocyte-platelet aggregates) and platelet transcriptome by RNA sequencing
- Follow-up
- 8 ± 4 weeks after treatment initiation
Main finding
As reported in the abstract
Platelet activation, on-treatment vs baseline · 8 ± 4 weeks
- Patients vs healthy controls: elevated P-selectin expression and enrichment of thromboinflammatory pathways
- Leuprolide: PAC-1 expression increased vs baseline in response to epinephrine, thrombin, adenosine diphosphate (ADP) and arachidonic acid (AA); P-selectin increased with epinephrine and higher with ADP and AA, though not statistically different
- Relugolix: AA-induced P-selectin expression and CD40 decreased
- Relugolix: platelet RNA sequencing showed down-regulation of pathways associated with platelet activation and aggregation
Observational data: associations, not effects.
Further findings
Leuprolide-treated patients on aspirin
- No increased AA-induced platelet activation (n = 6)
- In vitro P2Y12 inhibition of patient-derived platelets attenuated activation induced by epinephrine, ADP and AA
Original publication
Divergent Effects of GnRH Agonist and GnRH Antagonist Treatment on Platelet Activity and Transcriptome. JACC CardioOncol. Published August 2026. doi:10.
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