Relugolix and elagolix directly inhibit leiomyoma extracellular matrix production in 2-dimensional and 3-dimensional cell cultures

Reproductive Disease

VOLUME 3, ISSUE 3, P299-308, AUGUST 01, 2022


Danielle Wright, M.D., Joy Britten, M.D., Minnie Malik, Ph.D., William H. Catherino, M.D., Ph.D 



To determine the effect relugolix and elagolix have on the production of extracellular matrix (ECM) proteins in human leiomyoma cells.


Laboratory study.


University hospital.

Patient(s) or Animals

None. January 5, 2022 Cell culture, protein analysis, immunohistochemistry.

Main Outcome Measure(s)

Production of GnRHR, COL1A1, FN1, VCAN, p-ERK, & ERK in treated/untreated leiomyoma cells.


100 nM relugolix resulted in decreased production of COL1A1 at 24 (1.78 0.06-fold; P < .05) and 48 hours (1.92 0.14-fold; P < .05). Elagolix treatment resulted in a decrease in COL1A1 production at 24 but not 48 hours. In 2D and 3D, 100 nM relugolix resulted in decreased production of FN1 at 24 (1.7 ± 0.07-fold; P < .05) and 48 hours (1.8 ± 0.07-fold; P < .05); 100 nM elagolix resulted in decreased production of FN1 at 24 (1.7 ± 0.14-fold; P < .05) and 48 hours (2.0 ± 0.09-fold; P < .05). For cells treated with relugolix 100 nM resulted in decreased VCAN production by 48 hours (0.66 ± 0.07-fold; P < .05). Contrary to our 3D data, 2D elagolix-treated cells demonstrated a decrease in VCAN production that was identified only at 24 hours. For GnRHR, no significant difference between the drugs was seen at 24 hours; at 48 hours production was only significantly decreased for relugolix (P < .05). Comparing both drugs, there was a significant difference in the concentration of p-ERK to ERK at 24 hours (P < .05); there was no difference by 48 hours.


Our findings demonstrated that treatment with either drug can 1) decrease ECM protein production and 2) inhibit the MAPK pathway.

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