Bone mineral density with elagolix plus add-back therapy in women with heavy menstrual bleeding and uterine fibroids: open-label and post-treatment results of a 60-month phase 3 trial.
Level 3 - non-randomized controlled study
Open-label extension and follow-up cohort following a randomized trial
PubMed 41321663 · doi:10.1016/j.xagr.2025.100578
What was done
Phase 3b multicenter trial evaluating the long-term safety and bone mineral density (BMD) effects of elagolix (300 mg twice daily) plus hormonal add-back therapy (estradiol 1.0 mg/norethindrone acetate 0.5 mg daily) in premenopausal women aged 18–50 with heavy menstrual bleeding from uterine fibroids. Following an initial 12-month randomized, double-blind period (elagolix+add-back vs placebo), participants entered a 36-month open-label extension (OLE) where all received active therapy (months 13–48), followed by a 12-month post-treatment follow-up (months 49–60). BMD was measured every 6 months via dual-energy X-ray absorptiometry at the lumbar spine, total hip, and femoral neck.
What was found
A total of 277 patients entered the OLE, and 103 completed treatment. For continuous elagolix+add-back recipients, mean percent decrease in BMD from baseline remained <2% at the lumbar spine, total hip, and femoral neck at all visits through 48 months. A majority of patients with month-48 BMD reduction achieved partial or full recovery 12 months post-treatment. Decreased BMD was reported as an adverse event in 14.0% (27/193) of continuous users and 9.5% (8/84) of placebo-switch patients, leading to discontinuation in 12.4% (24/193) and 8.3% (7/84), respectively. Overall adverse events in the OLE occurred in 64.2% of continuous users and 70.2% of placebo-switch users, mostly mild or moderate.
Why it matters
Provides long-term data supporting the safety of extending elagolix plus add-back therapy beyond the standard 24-month duration, showing modest average bone loss that is largely reversible after cessation.
Limits
High attrition occurred, with only 37.2% (103/277) of enrolled extension participants completing 48 months of treatment. The extension lacked a blinded, concurrent placebo comparator group. BMD recovery was incomplete in a subset of patients 12 months after stopping therapy, and the study was not powered to detect rare clinical fracture outcomes.