Long-Term Relugolix Monotherapy for Uterine Fibroids: Surgery Avoidance in a Single-Center Retrospective Cohort Study

Relugolix monotherapy for uterine fibroids is approved in Japan for only 180 days, and almost all long-term evidence concerns relugolix combination therapy with estradiol and norethisterone acetate. We evaluated surgery avoidance, transition to menopause, symptom control, and bone mineral density (BMD) beyond 180 days.

We retrospectively reviewed 83 women with uterine fibroids given relugolix 40 mg monotherapy for at least 180 days at a single center between January 2015 and December 2024. Continuous variables are presented as median [interquartile range]; paired comparisons used the Wilcoxon signed-rank test, and group comparisons used the Mann-Whitney U test and Fisher's exact test (two-sided α = 0.05).

Median treatment duration was 327 days [239.5-420.0] (maximum 1030) and median age was 43 years [37-47]. Overall, 55.4% (46/83) avoided fibroid surgery and 8.4% (7/83) reached menopause without surgery; symptoms resolved or improved in 60.2% (50/83). Among women not wishing surgery, 90.0% (27/30) avoided it, whereas 77.3% (34/44) of those wishing surgery underwent it (Fisher's exact test, p < 0.001). Uterine volume fell from 658 to 502 cm³ (median within-patient reduction 19.0%, p < 0.001) and maximum fibroid diameter by 7.8% (p = 0.001). BMD trended downward at every site without reaching significance (lumbar spine -3.0%, p = 0.11). In addition, the median duration of the drug-free period for patients who measured bone mineral density was evaluated was 726 days (range: 7-2359 days).

Long-term relugolix monotherapy frequently enabled surgery avoidance and transition to menopause in women who declined surgery and controlled symptoms in most. Because estrogen add-back is absent, BMD monitoring and a prespecified exit strategy are essential.