Results of relugolix/estradiol/norethisterone acetate combination therapy in real-world clinical practice: Effectiveness, tolerability, and factors influencing discontinuation

Objective: To evaluate the real-world effectiveness, safety, and tolerability of relugolix/estradiol/norethisterone acetate combination therapy (relugolix CT) for managing symptomatic uterine fibroids in routine gynaecological practice. Methods: A retrospective, observational study was conducted at a tertiary hospital in Spain between June 2023 and January 2025. Adult women with symptomatic uterine fibroids treated with relugolix CT were included, either as a long-term treatment or preoperative management. Clinical outcomes were assessed at baseline, 6 months, and in a subset of patients, at 12 months. Primary endpoints included changes in total bleeding days, heavy menstrual bleeding (HMB) days, and UFS-QoL symptom severity scores (SSS), as well as treatment adherence and adverse events. Results: Among the 142 women who initiated treatment, Relugolix CT significantly reduced total bleeding days (from 12 to 2.2), HMB days (from 7.1 to 0.4), and UFS-QoL SSS (from 27.9 to 15.1) at 6 months (p < 0.05). Amenorrhea was achieved in 52.7 % at 6 months and 66 % at 12 months. Better clinical outcomes were linked to continued treatment. Adverse events were reported in 34.5 % of patients, primarily abdominal pain and vasomotor symptoms. Bone densitometry at 12 months showed no osteoporosis and mild osteopenia in a few patients. Discontinuation was most commonly due to planned surgery or perceived lack of efficacy. Conclusion: Relugolix CT demonstrates strong real-world effectiveness and tolerability for managing symptomatic uterine fibroids, with marked improvements in bleeding and quality of life, and a favourable safety profile.