Yselty
Evidence Grade C — Moderate human evidence. 54 published studies, 37 human. 10 registered clinical trials.
Linzagolix (Yselty) is an oral GnRH antagonist tablet for heavy menstrual bleeding from uterine fibroids — it is not a peptide. It has received marketing authorisation in some jurisdictions but not in the US. A unique feature is that lower doses partially suppress oestrogen without requiring the add-back hormone therapy that full-suppression approaches need.
54 published studies: 37 human, 1 animal, 5 in-vitro, 30 reviews
Linzagolix has received marketing authorisation in some jurisdictions for heavy menstrual bleeding associated with uterine fibroids. Phase III trials (PRIMROSE 1 and 2, total 1,012 patients) demonstrated responder rates of 56–94% across dose and add-back therapy combinations.
Linzagolix is not a peptide. Its partial-suppression dosing option (avoiding mandatory add-back therapy) distinguishes it from full-suppression GnRH antagonists. Its inclusion in this database reflects the competitive landscape for GnRH pathway therapeutics alongside peptide-based compounds.
Linzagolix competitively blocks the GnRH receptor on pituitary cells, reducing reproductive hormone secretion in a dose-dependent manner. At lower doses (100 mg), it produces partial oestrogen suppression (maintaining levels at 20–60 pg/mL), which may preserve bone density and manage vasomotor symptoms without mandatory add-back hormonal therapy. At higher doses (200 mg), near-complete suppression requires add-back therapy, similar to other GnRH antagonists.
Research suggests two large Phase III trials (total 1,012 patients) showed responder rates of 56-94% across different dose and add-back therapy combinations. UK health authorities have endorsed it for routine prescribing. However, the US application was withdrawn in August 2022 due to review deficiencies, and re-submission is being considered. The partial-suppression dosing option (avoiding mandatory add-back therapy) is a genuine differentiator from elagolix and relugolix. From the US perspective, linzagolix remains unavailable despite European authorisation.
A Clinical Study of KLH-2109 in Uterine Fibroids Patient With Menorrhagia and Pain
Extension to Study on Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain
Extension to Study on Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain (EDELWEISS 6)
Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain.
A Phase 3 Study to Confirm the Efficacy and Safety of Linzagolix to Treat Endometriosis-associated Pain
EMA Marketing Authorisation
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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.
