To evaluate the impact of Coenzyme Q-10 (CoQ-10) on the dysregulated synthesis of extracellular matrix proteins mediated by transforming growth factor beta 3 (TGF-ß3) in uterine leiomyomas DESIGN: Laboratory study SUBJECTS: None INTERVENTIONS: Treatment of immortalized uterine myometrial and leiomyoma cells to TGF-ß3 and CoQ-10 MAIN OUTCOME MEASURES: Protein concentration of collagen 1A1 (COL1A1), collagen 3A1 (COL3A1), collagen 11A1 (COL11A1), and fibronectin (FN1) was assessed through western blot analysis after treatment of immortalized uterine myometrial and leiomyoma cells with both TGF-ß3 and concentrations of CoQ-10 at 10, 50, and 100 μM concurrently for 24 hours. Immortalized uterine leiomyoma and myometrial cells exposed to TGF-ß3 for 24 hours demonstrated a significant upregulation of COL1A1, COL3A1, COL11A1, and FN1 as compared to untreated cells. In leiomyoma cells, concurrent treatment with CoQ-10 over the same timeframe revealed a dose-dependent decrease of these protein concentrations as compared to cells treated with TGF-ß3 alone. At the highest concentration of 100 μM CoQ-10, significant decreases in the amount of COL1A1 (0.59 + 0.10-fold, P = 0.03), COL3A1 (0.46 + 0.09-fold, P = 0.002), COL11A1 (0.53 + 0.09-fold, P = 0.01), and FN1 (0.56 + 0.09-fold, P = 0.002) were observed. Similarly, myometrial cells exposed to both TGF-ß3 and CoQ-10 demonstrated a dose-responsive decline in the amount of extracellular matrix protein as compared to cells exposed to TGF-ß3 alone. Significant reductions in the amount of COL1A1 (0.75 + 0.03-fold, P = 0.03), COL3A1 (0.48 + 0.06-fold, P = 0.04), COL11A1 (0.38 + 0.06, P = 0.003), and FN1 (0.69 + 0.04-fold, P = 0.006) were appreciated at 100 μM CoQ-10. CoQ-10 mitigated the aberrant production of key biomarkers of the extracellular matrix mediated by TGF-ß3 in uterine leiomyomas. Our findings highlight a promising nonhormonal compound that can counteract the fibroproliferative process inherent to leiomyomas.