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Clinical Trial
. 2025 Sep;124(3):523-533.
doi: 10.1016/j.fertnstert.2025.04.037. Epub 2025 May 2.

Efficacy and safety of relugolix combination therapy in women with uterine fibroids and adenomyosis: subgroup analysis of LIBERTY 1 and LIBERTY 2

William H Catherino  1 , Ayman Al-Hendy  2 , Souhil Zaim  3 , Nadia Bouzegaou  3 , Roberta Venturella  4 , Elizabeth A Stewart  5 , Rui Wu  6 , Silvia Vannuccini  7 , Julie S Perry  6 , Viatcheslav G Rakov  8 , Malcolm G Munro  9
Affiliations
Free article
Clinical Trial

Efficacy and safety of relugolix combination therapy in women with uterine fibroids and adenomyosis: subgroup analysis of LIBERTY 1 and LIBERTY 2

William H Catherino et al. Fertil Steril. 2025 Sep.
Free article

Abstract

Objective: To assess the effects of relugolix combination therapy in women with uterine fibroids (UFs) and concomitant ultrasound-diagnosed adenomyosis.

Design: This post hoc analysis used pooled data from completers of the pivotal LIBERTY studies. The subgroup of women with adenomyosis and UFs was compared with the overall study population on selected efficacy and safety endpoints.

Subjects: Premenopausal women (aged 18-50 years) with diagnosed UFs (confirmed by ultrasonography) and heavy menstrual bleeding (assessed by the alkaline hematin method).

Intervention: Once-daily relugolix combination therapy (40 mg relugolix, 1 mg estradiol, and 0.5 mg of norethindrone acetate) or placebo for 24 weeks, or delayed relugolix combination therapy (40 mg of relugolix monotherapy for 12 weeks, followed by relugolix combination therapy for 12 weeks).

Main outcome measures: Endpoints included the percentage of women with concomitant adenomyosis, the proportion of treatment responders (achieved or maintained a menstrual blood loss <80 mL and ≥50% reduction in menstrual blood loss volume from baseline over the last 35 days of treatment), the proportion of women achieving or maintaining amenorrhea over the last 35 days of treatment, and the change from baseline to week 24 in uterine volume and adverse events.

Results: A total of 111 women (18.2%) had a baseline diagnosis of concomitant adenomyosis (37 in the relugolix combination therapy group, 45 in the delayed relugolix combination therapy group, 29 in the placebo group) and were included in this analysis. Of women with adenomyosis, 83.8% in the relugolix combination therapy group were treatment responders compared with 27.6% in the placebo group. Amenorrhea was achieved in 64.9% of women with adenomyosis treated with relugolix combination therapy and in 6.9% of women treated with placebo. The least square mean uterine volume of women with adenomyosis decreased by 22.2% and 5.8% in the relugolix combination therapy and placebo groups, respectively. Results for the above outcomes in the relugolix combination therapy population were similar to the delayed relugolix combination therapy group.

Conclusion: Efficacy outcomes in women with adenomyosis and UFs were comparable with those in women from the overall LIBERTY study population.

Clinical trial identification number: LIBERTY 1, 2016-003727-27 (EudraCT) and NCT03049735; LIBERTY 2, 2016-005113-50 (EudraCT) and NCT03103087.

Keywords: Uterine fibroids; adenomyosis; heavy menstrual bleeding; oral gonadotropin-releasing hormone antagonists; relugolix combination therapy.

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Conflict of interest statement

Declaration of Interests W.H.C. is a consultant to Sumitomo Pharma America, Bayer Pharma, and Pfizer. A.A.-H. is a consultant for AbbVie, Bayer, Novartis, ObsEva, Pfizer, and Sumitomo Pharma America; had a research agreement with Crila; has research grants with the National Institutes of Health; and has several patents. S.Z. is an employee of Clario. N.B. has nothing to disclose. R.V. is a consultant for Sumitomo Pharma America. Over the last 36 months, E.A.S. has received grant/research financial support from the National Institutes for Health related to uterine fibroids (R01HD109127-01A1, and P50HD115283, P50HS023418) and adenomyosis (5R01HD105714); served as a consultant for AbbVie, Alnylam Pharmaceuticals, and Sumitomo Pharma America; holds a patent for Methods and Compounds for Treatment of Abnormal Uterine Bleeding (US Patent 6440445), which has no commercial activity; and has received royalties from UpToDate and payments for the development of educational content from the Med Learning Group, MED-IQ, Omnia, Physicians Educational Resources, and Web-MD; serves as an unpaid advisor to the Fibroid Foundation and the unpaid treasurer of the International Gynecologic Society. R.W. is a previous employee of Sumitomo Pharma America, Inc. S.V. has received consultancy fees from Gedeon Richter and Theramex. J.S.P. is a previous employee of Sumitomo Pharma America, Inc. V.G.R. is an employee of Sumitomo Pharma Switzerland GmbH. Over the past 36 months, M.G.M. has been a consultant for AbbVie Inc, Myovant Sciences Inc. (Sumitomo Pharma America, Inc.), Daiichi-Sankyo, Pharmacosmos, Hologic Inc, and Shield Therapeutics.

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