We here describe a case of the prolapse of pedunculated submucosal leiomyoma 
through the cervix during the treatment of a gonadotropin-releasing hormone 
(GnRH) antagonist relugolix. We also present the literature review of the cases 
of leiomyoma prolapse during GnRH modulators. A 55-year-old woman with atypical 
vaginal bleeding diagnosed submucosal uterine fibroid 6 cm in diameter, and 
daily oral administration of relugolix was conducted. On the 35th day of the 
administration, heavy vaginal bleeding suddenly occurred due to leiomyoma 
prolapse. Finally, she underwent abdominal hysterectomy to treat heavy bleeding. 
To date, six cases of leiomyoma prolapse during GnRH modulators have been 
reported, in which all the previous cases were treated with GnRH agonists. This 
is the first case report of leiomyoma prolapse during GnRH antagonist treatment. 
Notably, leiomyoma prolapse is a possible common adverse effect of GnRH 
modulators for the treatment of submucosal leiomyoma, which is caused by rapid 
decrease in its volume.