Orilissa, Oriahnn
Evidence Grade A — Regulatory approved. 189 published studies. 30 registered clinical trials.
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Elagolix (sold as Orilissa for endometriosis and as part of Oriahnn for uterine fibroids) is a daily oral tablet that reduces the body's production of oestrogen. It is not a peptide — it is a small molecule drug — but it is included in this database because it targets the same hormonal pathway as peptide-based GnRH treatments. It was the first oral GnRH antagonist approved in the US.
189 published studies: 128 human, 1 animal, 17 in-vitro, 62 reviews
Elagolix is marketed as Orilissa for endometriosis pain (approved July 2018) and as a component of Oriahnn for heavy menstrual bleeding from uterine fibroids (approved May 2020). Oriahnn combines elagolix with low-dose hormone add-back therapy to mitigate bone density loss.
Clinical trials showed that the higher dose reduced menstrual pain in approximately 76% of patients and non-menstrual pelvic pain in about 55% at six months. The main limitation is bone density loss with prolonged use, which the add-back therapy in Oriahnn helps address. As an oral tablet taken daily, it offers a fundamentally different experience from injectable or implanted hormone treatments, though it requires consistent daily dosing. It is important to note that elagolix is not a peptide — it is included in this database because it targets the same GnRH pathway as peptide-based treatments.
Elagolix blocks the GnRH receptor in the pituitary gland, reducing the signals that drive oestrogen and progesterone production. What sets it apart is dose flexibility: at a lower dose (150 mg once daily), it partially suppresses oestrogen, managing pain while preserving enough hormone to protect bone density. At a higher dose (200 mg twice daily), suppression is more complete. This tuneable approach distinguishes it from injectable GnRH treatments, which generally produce near-complete hormone suppression regardless of dose.
Clinical trials showed that the higher dose of elagolix reduced menstrual pain in about 76% of endometriosis patients and non-menstrual pelvic pain in approximately 55% at six months. The key advantage over injectable hormone treatments is the oral tablet format with dose flexibility — lower doses partially suppress oestrogen (managing pain while preserving bone density), while higher doses provide more complete suppression. The main limitation is bone density loss with prolonged use, which restricts treatment duration to 6-24 months depending on the dose. The Oriahnn product for fibroids addresses this by including low-dose hormone add-back therapy. Commercially, elagolix has been overshadowed by relugolix combination therapy (Myfembree), which offers once-daily dosing with built-in hormonal add-back in a single tablet.
Role of Menopause in Thermoregulation
Brain Blood Flow Responses to Stress: Sex Differences
Pre-IVF Treatment With a GnRH Antagonist in Women With endometriosis_temp
A Study to Evaluate Changes in Hair in Adult Participants Taking Oral Oriahnn Capsules With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF)
A Clinical Trial to Evaluate Efficacy and Safety of Elagolix Tablets in Women With Moderate or Severe Endometriosis-associated Pain
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Histrelin is available as Supprelin LA for central precocious puberty (approved 2007). The Vantas implant for prostate cancer was approved in 2004 but discontinued in 2021. The implant requires a minor surgical procedure for insertion and removal/replacement each year. Supprelin LA's main clinical advantage is its 12-month duration — the longest of any GnRH agonist — which is particularly valuable in paediatric patients where treatment compliance over years is important. Clinical studies demonstrated effective suppression of puberty markers in over 97% of patients. The implant has also seen significant off-label use in gender-affirming care as a puberty blocker, where its annual dosing schedule offers practical benefits for adolescent patients and their families.
Goserelin is marketed as Zoladex by AstraZeneca, available as 3.6 mg monthly and 10.8 mg three-monthly subcutaneous implants. First approved in 1989, it is used in advanced prostate cancer, premenopausal breast cancer, endometriosis, and for thinning the uterine lining before surgical procedures. Goserelin achieves castrate-level testosterone suppression (below 50 ng/dL) within two to four weeks. Its unique implant delivery system means there is no liquid injection, reconstitution, or refrigeration required — a practical advantage in some clinical settings. Like all GnRH agonists, it causes an initial hormone flare before suppression takes effect. Goserelin holds an important niche in breast cancer treatment, where it is used to suppress ovarian function in premenopausal women with hormone-receptor-positive disease, often in combination with aromatase inhibitors.
Nafarelin is marketed as Synarel (approved 1990) for endometriosis and central precocious puberty. It requires administration as one spray in each nostril twice daily — a higher frequency than injectable alternatives but avoids needles entirely, which can be a significant advantage for some patients, particularly children. Clinical trials showed symptom improvement in 75–92% of endometriosis patients. However, absorption can be affected by nasal congestion or concurrent use of nasal decongestants, which can be a practical limitation. As with all GnRH agonists, prolonged use leads to bone density loss, and treatment for endometriosis is typically limited to six months. Nafarelin occupies a niche for patients who prefer non-injectable hormone suppression, though it has become less commonly prescribed as longer-acting depot injections and oral alternatives have become available.
