Adequacy of Estradiol/Norethindrone Acetate to Mitigate Dose-Dependent and Progressive Decline in Bone Mineral Density Observed with Gonadotropin-Releasing Hormone Receptor Agonism/Antagonism - IP01-D
Friday, May 17, 2024
10:30 AM – 11:30 AM PDT
Location: Hall C
Authors:Julie Perry MD; Sawsan As-Sanie MD; Rachel Wagman MD; Dongmei Zhai PhD; Neil Johnson MD
Emeritus Director Oregon Osteoporosis Center Portland, OR, United States
Introduction: Bone mineral density (BMD) data from the relugolix monotherapy endometriosis program were used to investigate the impact of relugolix combination therapy (Relugolix-CT: relugolix 40mg, estradiol 1mg, norethindrone acetate 0.5mg) on bone loss. Methods: Phase 2 studies (NCT01458301/NCT01452685): 487 women were randomized to placebo, gonadotropin-releasing hormone (GnRH) antagonist relugolix (10mg, 20mg, or 40mg), or GnRH agonist leuprorelin for 24 weeks. Phase 3 study (NCT03931915): 335 women were randomized to relugolix 40mg or leuprorelin for 24 weeks. Phase 3 study (NCT03654274): 799 women previously treated with placebo or Relugolix-CT for 24 weeks, or delayed Relugolix-CT (relugolix 40mg followed by Relugolix-CT; 12 weeks each), received 80 weeks of Relugolix-CT. All studies were Institutional Review Board approved. Percent changes in lumbar spine BMD were assessed. Results: Progressive and dose-dependent declines in BMD were observed with relugolix monotherapy; changes were comparable at Week 12 and 24 between relugolix 40mg (–2.10% and –4.90%, respectively) and leuprorelin (–2.21% and –4.43%). In women treated with relugolix monotherapy for 12 weeks who transitioned to Relugolix-CT, there was a decline in BMD at Week 12 (–1.72%), followed by stabilization at Week 24 (–1.86%), with upward drift for the remainder of treatment (Week 104: –0.56%). Women treated continuously with Relugolix-CT demonstrated a BMD decrease of less than 1% from baseline at Week 24 (–0.92%), followed by stabilization by Week 36 (–0.66%) and plateau through Week 104 (–0.45%). Conclusion/Implications: At initiation, Relugolix-CT preserves BMD from deleterious effects of ovarian suppression with GnRH receptor agonist/antagonist monotherapy, supporting the value of combination therapy.
Disclosure(s):
Michael R. McClung, MD: Alexion: Advisory Committee/Board Member (Ongoing); Amgen: Consultant (Ongoing), Speaker/Honoraria (Ongoing); Myovant: Consultant (Ongoing); Radius Health: Advisory Committee/Board Member (Ongoing)