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

Abstract

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.