Relugolix reduces leiomyoma extracellular matrix production via the TGF β pathway.

Objective: To determine if the oral GnRH antagonist relugolix affects leiomyoma extracellular matrix production through the TGF β pathway DESIGN: Laboratory Study SUBJECTS: None.

Intervention: Exposure of human leiomyoma cells to TGF β and/or relugolix MAIN OUTCOME MEASURES: Production of TGF β, pSMAD2/3, SMAD2/3, COL1A1, FN1 and VCAN in treated and untreated leiomyoma cells RESULTS: TGF β3 production was decreased at 24 hours with relugolix at 10nM (0.80 + 0.09 fold, p 0.04) and 100nM (0.86 + 0.06 fold, p0.03) and at 48 hours with relugolix 1nM (0.86 + 0.05 fold, p0.01) and 100nM (0.86 + 0.06 fold, p0.04). pSMAD2/3 was decreased at 24 hours with relugolix 1nM (0.71 + 0.01 fold, p0.002), 10nM (0.68 + 0.01 fold, p0.001) and 100nM (0.41 + 0.10 fold, p0.004). When compared to relugolix treatment alone at the same concentration, combination treatment at 24 hours resulted in significantly increased COL1A1, FN1 and VCAN production with relugolix 1nM, 10nM and 100nM. At 48 hours, combination treatment resulted significantly increased COL1A1, FN1 and VCAN production with relugolix 10nM and 100nM.

Conclusion: Relugolix regulated leiomyoma size by decreasing COL1A1, FN1 and VCAN production. This effect is at least partly through the TGF β pathway.