Gonadotropin-Releasing Hormone Receptor Antagonist Mono- and Combination Therapy With Estradiol/Norethindrone Acetate Add-Back: Pharmacodynamics and Safety of OBE2109

Oliver Pohl, Line Marchand, Neil Fawkes, Jean-Pierre Gotteland, Jean‐Pierre Gotteland, Ernest Loumaye
The Journal of clinical endocrinology and metabolism · 2017 · vol. 103(2) , pp. 497–504 · doi:10.1210/jc.2017-01875 · PMID:29216361 · W2771800427
RCT OA: bronze CC0 ⤵ 12 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-12 ⓘ

OBE2109 potently lowered estradiol levels and induced amenorrhea, with add-back therapy mitigating bone marker increases and partially affecting bleeding control.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

CONTEXT: OBE2109 is a potent, oral gonadotropin-releasing hormone receptor antagonist being developed for the treatment of sex-hormone-dependent diseases in women. OBJECTIVE: We assessed the pharmacodynamics and safety of OBE2109 alone and combined with estradiol (E2)/norethindrone acetate (NETA) add-back therapy on E2 levels and vaginal bleeding. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center, open-label, randomized, parallel-group study in 76 healthy premenopausal women. INTERVENTIONS: Women were randomly assigned to take the following doses (in milligrams) once daily for 6 weeks: OBE2109, 100 or 200; or OBE2109/E2/NETA, 100/0.5/0.1, or 100/1.0/0.5, or 200/1.0/0.5. MAIN OUTCOME MEASURES: E2 concentrations, bleeding pattern, exploratory bone metabolism biomarkers, and adverse events. RESULTS: OBE2109 100 mg and 200 mg alone reduced E2 levels to reach median levels of 19.5 and 3.2 pg/mL, respectively, at week 4. Median E2 levels after combined OBE2109/add-back therapy ranged between 25 and 40 pg/mL. OBE2109 100 mg or 200 mg alone induced amenorrhea. By day 15, >85% of women had no vaginal bleeding during the last 4 weeks of treatment. Add-back therapy partially impaired bleeding control: The highest amenorrhea rate (53%) was observed with OBE2109 100 mg/1.0 mg/0.5 mg. The addition of E2/NETA, particularly at 1 mg/0.5 mg, mitigated the increase of two bone markers induced by OBE2109 200 mg. CONCLUSION: OBE2109 promptly lowered E2 levels. Add-back therapy may be required to prevent adverse effects on bone in women treated with the 200-mg dose (at 100 mg in some women). These results provide a basis for OBE2109 regimen selection to treat sex-hormone-dependent diseases.

My notes (saved in your browser only)

MeSH descriptors

Estradiol Estradiol Estradiol Estradiol Hormone Antagonists Hormone Antagonists Hormone Antagonists Hormone Antagonists Norethindrone Norethindrone Norethindrone Norethindrone Organic Chemicals Organic Chemicals Organic Chemicals Organic Chemicals Receptors, LHRH Receptors, LHRH Administration, Oral Adult

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (18)

Cited by (13)

Source provenance

openalex
last seen: 2026-05-10T10:52:07.745204+00:00
pubmed
last seen: 2026-10-08T21:20:57.725456+00:00
License: CC0 · commercial use OK