Triptorelin

A synthetic decapeptide GnRH agonist (D-Trp6-GnRH) that briefly stimulates and then durably suppresses gonadotropin release, FDA-approved as pamoate depots for advanced prostate cancer (Trelstar, 2000) and central precocious puberty (Triptodur, 2017).

Also referenced as: Triptorelin pamoate, Triptorelin acetate, Triptorelin embonate, Trelstar, Triptodur, Decapeptyl, Gonapeptyl, Diphereline, Salvacyl, D-Trp6-GnRH, D-Trp6-LHRH, D-Trp-6-LHRH

Also appears in: Other

COA Public product evidence No certificate records are bound to a tracked Triptorelin product page A record counts here only when a vendor publishes a certificate against one of its own tracked Triptorelin product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

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What is Triptorelin?

Triptorelin is a synthetic decapeptide analog of gonadotropin-releasing hormone with the sequence pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2: native GnRH with a single D-tryptophan swapped in at position 6, which is why older literature calls it D-Trp6-LHRH. That one substitution makes it resistant to enzymatic cleavage and far more potent at the pituitary GnRH receptor, and it reached the clinic as sustained-release depots marketed in the U.S. as Trelstar (pamoate salt, approved June 15, 2000 as a new molecular entity for advanced prostate cancer) and Triptodur (pamoate, approved June 29, 2017 for central precocious puberty in children aged 2 and older).

Outside the pharmacy it occupies a specific niche: it is the GnRH agonist that research-peptide catalogs actually stock, typically as an acetate-salt lyophilized powder rather than the clinical pamoate microgranules, and it is sought for its effect on the hypothalamic-pituitary-testicular axis. That interest rests on the drug’s brief stimulatory phase, not on its approved suppressive use, and the human evidence behind it is a single published case.

How it works

• Position-6 D-amino acid substitution confers superagonism — replacing glycine-6 with a D-amino acid stabilizes the peptide’s bioactive conformation and protects it from degradation; the D-Trp6 analog emerged from Schally’s laboratory as one of the most active in the series (Coy et al., Journal of Medicinal Chemistry, 1976, 19(3):423–425). FDA labeling reports triptorelin as 100-fold more active than native GnRH at releasing LH from cultured rat pituitary cells and 20-fold more active at displacing GnRH from pituitary receptors in vitro, and triptorelin pamoate as 13-fold more potent at releasing LH and 21-fold more potent at releasing FSH in animal studies (Trelstar labeling, section 12.1)
• Flare first — after the first dose there is a transient surge in LH, FSH, testosterone, and estradiol; with the 3.75 mg depot, serum testosterone in healthy volunteers peaked on day 4 before falling, and with the 11.25 mg and 22.5 mg depots in men with prostate cancer it peaked on days 2–3 (Trelstar labeling, section 12.2). In the first randomized trial of the long-acting microcapsules, 3 of 41 men had a clinical disease flare within ten days of starting that resolved once testosterone reached castrate levels (Parmar et al., Lancet, 1985, 2(8466):1201–1205)
• Then desensitization and downregulation — continuous receptor occupancy desensitizes pituitary gonadotrophs; LH and FSH secretion falls to a sustained low by two to four weeks, testicular steroidogenesis is markedly reduced, and testosterone reaches levels typical of surgical castration. In the pivotal 3.75 mg trial, 124 of 126 evaluable men (98.4%) had serum LH at or below 1.0 IU/L two hours after a repeat injection on day 85, the direct readout of receptor desensitization (Trelstar labeling, section 14; Heyns et al., BJU International, 2003, 92(3):226–231)
• The therapeutic effect is downstream sex-steroid deprivation — triptorelin has no cytotoxic action of its own; prostate tumors, gonadotropin-driven puberty, and hormone-receptor-positive breast tissue become quiescent because the gonadal steroids that maintain them are withdrawn, which is why labeling notes these effects are usually reversible after cessation (Trelstar labeling, section 12.2)

Research status

Triptorelin has roughly four decades of clinical evidence in oncology, pediatric endocrinology, and reproductive medicine, plus a large off-label literature in assisted reproduction. The research-market use case has essentially none.

Prostate cancer (approved). Parmar et al. randomized 79 men with advanced prostatic carcinoma to slow-release D-Trp-6-LHRH microcapsules (n = 41) or orchidectomy (n = 38) and found equivalent testosterone suppression, similar reductions in prostatic acid phosphatase, and response-or-stabilization in 87% versus 81% (Lancet, 1985, 2(8466):1201–1205). The U.S. registration trial for the 3.75 mg monthly depot (Heyns et al.) treated 284 men with triptorelin pamoate 3.75 mg or leuprolide 7.5 mg every 28 days for nine injections: castration by day 29 was less frequent with triptorelin (91.2% vs 99.3%) but equivalent by day 57 (97.7% vs 97.1%), with cumulative maintenance of castration through day 253 of 96.2% vs 91.2% (BJU International, 2003, 92(3):226–231). The 9-month survival difference reported in that paper (97.0% vs 90.5%, P = 0.033) was a secondary endpoint in a trial not designed for survival and has not been treated as a class difference. The 11.25 mg 3-month strength (NDA 021288, approved June 29, 2001) was supported by a 346-man randomized comparison against the monthly depot (97.7% castrate by day 29; 94.4% maintained from day 57 through day 253), and the 22.5 mg 6-month strength (NDA 022437, approved March 10, 2010) by a 120-man non-comparative Phase 3 in South Africa in which 97.5% were castrate by day 29 and 93.0% maintained castration over months 2–12; hot flushes occurred in 71.7% (Lundström et al., Clinical Drug Investigation, 2009, 29(12):757–765; NCT00751790).

Central precocious puberty (approved). Triptodur’s pivotal study was a single-arm, open-label, 48-week Phase 3 in 44 treatment-naive children (39 girls aged 2–8, 5 boys aged 2–9) at 18 centers in the U.S., Chile, and Mexico, receiving two 22.5 mg injections 24 weeks apart. Stimulated LH was suppressed to prepubertal levels in 93.2% (41/44) at month 6, the primary endpoint, and 97.7% (43/44) at month 12, with no unexpected drug-related adverse events (Klein et al., Journal of Pediatric Endocrinology and Metabolism, 2016, 29(11):1241–1248). Triptodur was approved with orphan status; its U.S. labeling was last revised in September 2025.

Breast cancer (not U.S.-approved; Phase 3 evidence). Triptorelin was the ovarian-suppression agent used by most participants in SOFT and TEXT, the two International Breast Cancer Study Group trials that reshaped adjuvant endocrine therapy for premenopausal hormone-receptor-positive disease. At 8 years in SOFT, disease-free survival was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression; overall survival was 91.5%, 93.3%, and 92.1%. Grade 3 or higher adverse events rose from 24.6% with tamoxifen alone to 31.0–32.3% in the ovarian-suppression arms (Francis et al., New England Journal of Medicine, 2018, 379(2):122–137; NCT00066690, NCT00066703). Separately, the PROMISE-GIM6 trial randomized 281 premenopausal women to chemotherapy with or without triptorelin for ovarian protection: 5-year menstrual resumption was 72.6% vs 64.0% (unadjusted HR 1.28, P = 0.07; age-adjusted HR 1.48, P = 0.006), with no significant difference in pregnancies or disease-free survival (Lambertini et al., JAMA, 2015, 314(24):2632–2640; NCT00311636). On the strength of SOFT and TEXT, the UK MHRA and 14 other European regulators approved an adjuvant early-breast-cancer indication for Decapeptyl (triptorelin pamoate) in March 2017; European triptorelin depots also carry endometriosis and uterine-fibroid indications. U.S. labeling covers none of these.

The research-market rationale. The idea that one exposure to a GnRH agonist can “restart” a suppressed hypothalamic-pituitary-testicular axis traces to a single case report. Pirola et al. described a 34-year-old man with hypogonadotropic hypogonadism after chronic use of internet-purchased anabolic steroids who received a single dose of triptorelin as a diagnostic stimulation test; his testosterone was in the normal range within a month and symptoms resolved (Fertility and Sterility, 2010, 94(6):2331.e1–e3). That is a diagnostic test in one patient whose axis may have been recovering spontaneously, with no control, no replication, and no randomized or even prospective follow-up study in the 15 years since. No registered trial tests triptorelin for recovery from anabolic-steroid-induced hypogonadism.

Failures and stopped programs. An Ipsen Phase 3 of a subcutaneous 4-month sustained-release triptorelin formulation in prostate cancer (NCT00415246, started November 2006, planned enrollment 100) was terminated because preliminary data did not support sustained blood levels for the full 4 months in all patients, and no 4-month product was ever approved. Two 2025 registrations for a new triptorelin depot, FP-014 at 11.25 mg and 22.5 mg (NCT06795178, NCT06795191), were withdrawn before enrolling for stated business reasons. A U.S. comparative trial of Trelstar against leuprolide and goserelin (NCT02749825) was terminated for withdrawal of funding. Cochrane’s 2019 review of long-term GnRH agonist pretreatment before IVF in women with endometriosis, a common off-label use of triptorelin, found the evidence too uncertain to support the practice (Georgiou et al., Cochrane Database of Systematic Reviews, 2019, Issue 11, CD013240).

Trial registry picture. ClinicalTrials.gov lists 298 studies with triptorelin as an intervention as of October 2026: 72 Phase 3, 56 Phase 4, 63 Phase 2, plus 14 combined Phase 2/3. The conditions split roughly evenly between prostate cancer (about 56 records) and infertility or IVF (about 75 across the infertility and IVF labels, mostly agonist-trigger and downregulation protocols), followed by breast cancer (19), endometriosis (9), central precocious puberty (7), and polycystic ovary syndrome (7). Twenty are terminated and seven withdrawn, almost all for accrual or funding rather than safety.

Regulatory currency. No new triptorelin product or indication was approved in the U.S. in 2025 or 2026; Drugs@FDA still lists only the three Trelstar NDAs and Triptodur. All four NDAs received labeling supplements on September 23, 2025 adding a severe cutaneous adverse reactions warning under an FDA class-wide safety labeling change for GnRH agonists, and the Trelstar label was revised again in June 2026.

Common dosage forms

• Intramuscular depot microgranules (pamoate) — Trelstar in 3.75 mg (4-week), 11.25 mg (12-week), and 22.5 mg (24-week) single-dose vials of lyophilized triptorelin pamoate in a poly-d,l-lactide-co-glycolide matrix, supplied as a kit with a vial adapter and a prefilled 2 mL sterile-water syringe. Strengths are expressed in triptorelin base units
• Pediatric 6-month depot (pamoate) — Triptodur 22.5 mg (equivalent to 31 mg triptorelin pamoate) extended-release kit with a prefilled 2 mL diluent syringe
• Ex-U.S. depots in both salts — Decapeptyl SR 11.25 mg and 22.5 mg are pamoate; Decapeptyl SR 3 mg and Gonapeptyl Depot 3.75 mg are acetate. The UK 11.25 mg product was switched from acetate to pamoate, and the Scottish Medicines Consortium accepted the pamoate depot on the basis of demonstrated bioequivalence between the salts, so the salt is a formulation choice rather than a pharmacological one
• Daily subcutaneous solution (acetate) — a 0.1 mg/mL triptorelin acetate prefilled syringe (Decapeptyl 0.1 mg) exists in Europe for short-course downregulation in assisted reproduction; there is no U.S.-approved daily triptorelin
• Research-market vials — lyophilized triptorelin acetate powder, most commonly labeled 2 mg per vial, with bulk powder offered at higher weights. None of this material carries the biodegradable microgranule matrix that gives the clinical products their weeks-to-months release; reconstituted, it is a plain aqueous solution with a half-life measured in hours

Key considerations

• This is an approved prescription drug, not an investigational peptide. Triptorelin has held FDA approval since 2000 in prostate cancer and since 2017 in central precocious puberty, and it is a licensed medicine across Europe for additional indications; the FDA Approved status reflects that FDA-approved drug products containing the molecule exist. “Research use only” material is a gray-market presentation of a pharmacy drug, without the release testing, sterility assurance, or engineered depot that the licensed products carry.
• The research-market rationale inverts the pharmacology. Every approved use of triptorelin exploits sustained suppression; the research-market interest exploits the transient flare that labeling treats as an adverse event to be monitored. The human basis for an axis “restart” is one 2010 case report describing a diagnostic test, with no controlled data, no replication, and no registered trial. GnRH and its analogues, triptorelin among them, are also named examples in WADA’s S2 class of peptide hormones, growth factors, related substances, and mimetics.
• The safety signals are class-wide and labeled. Trelstar’s current labeling warns of anaphylaxis and angioedema, tumor flare with bone pain and urethral or bladder-outlet obstruction in the first weeks, metabolic changes including hyperglycemia and post-marketing non-alcoholic fatty liver disease, increased risk of myocardial infarction, sudden cardiac death and stroke in men, convulsions, QT/QTc prolongation, embryo-fetal toxicity, and, added in 2025, severe cutaneous adverse reactions including SJS/TEN and DRESS. Post-marketing reports include pituitary apoplexy, mostly within two weeks of a first dose and sometimes within the first hour. Triptodur’s label adds psychiatric events and pseudotumor cerebri in children.
• Pamoate versus acetate is about release, not activity. The pamoate (embonate) salt is poorly soluble and is what the lactide-glycolide microgranule depots are built on; the acetate is water-soluble and appears in the daily European product, some older depots, and essentially all research-market powder. Bioequivalence between the two salts has been demonstrated in depot form, so a product’s duration comes from its matrix, not its counterion.
• Naming confusion runs in two directions. Research catalogs often list triptorelin as “GnRH” or “GnRH (triptorelin),” but it is not native GnRH (gonadorelin), which has a half-life of minutes and is used clinically in pulsatile pumps; the D-Trp6 substitution is the whole point. In the other direction, triptorelin is routinely conflated with leuprolide and “Lupron,” a different nonapeptide with D-Leu6 and a C-terminal ethylamide. GnRH antagonists (cetrorelix, degarelix, relugolix) suppress the axis immediately with no flare, the opposite initial effect.