Evidence Grade C — Moderate human evidence. 58 published studies, 39 human. 16 registered clinical trials.
Medically reviewed by a licensed medical professional
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.
Linzagolix is also known by these brand and alternate names:
58 published studies: 39 human, 1 animal, 5 in-vitro, 31 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 However, the US application was withdrawn in August 2022 due to review deficiencies, and re-submission is being considered.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.
PeptideTrace tracks 16 registered clinical trials for Linzagolix sourced from ClinicalTrials.gov.
A Phase II Randomized Open Label Study of KLH-2109 in Patients With Endometriosis
A Randomized Open Label Study of KLH-2109 in Patients With Endometriosis(1)
A Randomized, Placebo-controlled, Double-blind Study of KLH-2109 in Patients With Endometriosis (2)
A Clinical Study of KLH-2109 in Patients With Endometriosis
A Clinical Study of KLH-2109 in Uterine Fibroids Patient With Menorrhagia and Pain
EMA Marketing Authorisation
Linzagolix (brand name Yselty) is an oral GnRH receptor antagonist. NOTE: This is a small molecule, NOT a peptide. Molecular weight 508.42 Da (free base); 611.59 Da as choline salt (marketed form). Molecular formula: C22H15F3N2O7S. CAS number: 935283-04-8 (free base); 1321816-57-2 (choline salt). Developed by Kissei Pharmaceutical with EU commercialization handled by Theramex. The compound received EU marketing authorization for uterine fibroids in June 2022 and for endometriosis in November 2024. However, the US FDA NDA was withdrawn in August 2022 due to review deficiencies, and rights returned to Kissei.
Research suggests linzagolix competitively blocks pituitary GnRH receptors (IC50 36.7 nM), dose-dependently reducing LH, FSH, estradiol, and progesterone secretion. At 100 mg, the compound maintains estradiol at 20-60 pg/mL representing partial suppression without mandatory add-back hormonal therapy. At 200 mg, full suppression below 20 pg/mL occurs, requiring hormonal add-back. This dose-dependent partial suppression profile uniquely allows uterine fibroid and endometriosis management while minimizing bone density loss and vasomotor symptoms at lower doses.
Research suggests the PRIMROSE 1 and PRIMROSE 2 Phase 3 trials (NCT03070899 and NCT03070951; total N=1,012) demonstrated responder rates of 56.4-93.9% across dose and add-back therapy combinations versus 29.4-35.0% with placebo (P values 0.003 or less for all comparisons). The 200 mg plus add-back therapy arm achieved 93.9% response in PRIMROSE 2. Amenorrhea rates reached approximately 80% with the 200 mg plus add-back therapy arm. Bone mineral density was well preserved at the 100 mg dose without add-back, remaining comparable to placebo at week 52.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Carbetocin has not been approved by the FDA. It is registered in over 80 countries for prevention of uterine atony and excessive bleeding after caesarean delivery. A heat-stable formulation was added to the WHO Essential Medicines List in 2019. The CHAMPION trial (WHO, 2018; over 29,000 women) compared a heat-stable carbetocin formulation to oxytocin for preventing postpartum haemorrhage after vaginal delivery, and found it to be non-inferior. The heat-stable formulation addresses a significant limitation of oxytocin, which degrades in warm climates without refrigeration — a major concern in low-resource settings where postpartum haemorrhage causes the most deaths. Its regulatory status varies by jurisdiction.
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.
Triptorelin is marketed as Trelstar (approved 2000) for advanced prostate cancer, available as intramuscular depot injections in monthly (3.75 mg), three-monthly (11.25 mg), and six-monthly (22.5 mg) formulations. It is also widely used internationally for gender-affirming care and central precocious puberty. Triptorelin is one of the most commonly used GnRH agonists globally, though it faces the same competitive pressure as other agents in this class from newer oral GnRH antagonists like relugolix, which avoid the initial hormone flare and offer potential cardiovascular advantages. Clinical data demonstrate reliable testosterone suppression comparable to other GnRH agonists in this class.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
