Triptorelin
Also known as: Decapeptyl, Trelstar, Triptodur, Triptorelin pamoate, Triptorelin acetate
Evidence: Clinical
Overview
Synthetic decapeptide GnRH agonist; one dose triggers an LH and FSH surge, continued exposure suppresses them. FDA-labeled depots treat prostate cancer (Trelstar) and precocious puberty (Triptodur).
Triptorelin is GnRH with D-tryptophan at position 6, which makes it far more potent and longer lived than the native hormone. A first dose causes an LH and FSH surge and a testosterone or estrogen flare; continued exposure desensitizes pituitary receptors and suppresses sex hormones to castrate levels. In the US it is approved by the FDA as Trelstar depots (3.75, 11.25 and 22.5 mg, from 2000) for advanced prostate cancer and as Triptodur (22.5 mg every 24 weeks, 2017) for central precocious puberty. Endometriosis and uterine fibroids are not US indications. A single 0.2 mg dose has been used in IVF to trigger oocyte maturation (Fauser 2002). Vendor research vials are not the labeled depots.
Benefits
Testosterone suppression in advanced prostate cancer (FDA-labeled depot), pubertal suppression in central precocious puberty (FDA-labeled depot), oocyte-maturation trigger in IVF (human trials, not a US indication), single-dose LH surge for post-cycle use (community, no trial)
Dosing reference
- Research dose
- Community protocol: 100 mcg once (anecdotal). US labels cover depot products for prostate cancer and central precocious puberty only.
- Range
- 100 mcg, Single dose
- Reconstitution
- 1 mL bacteriostatic water
- Common vial sizes
- 0.1 mg, 2 mg
A single 100 mcg dose is a community protocol (anecdotal); clinical ovulation-trigger doses are around 200 mcg. Repeated or depot exposure suppresses the HPG axis and causes hypogonadism, with hot flushes, loss of libido, mood changes and bone mineral density loss on prolonged use. The initial hormone flare can transiently worsen hormone-sensitive conditions.
Mechanism
Triptorelin is a synthetic decapeptide agonist of the GnRH receptor. In vitro it was 100-fold more active than native GnRH at releasing LH from rat pituitary cells and 20-fold more active at displacing labeled GnRH from pituitary receptors (Trelstar label). Acute exposure releases LH and FSH; repeated or depot exposure desensitizes the gonadotrophs, and the label reports LH at or below 1 IU/L two hours after repeat dosing in 98% of men, which is the basis of medical castration. The post-cycle use relies on the acute surge from a single dose without the follow-on suppression; that rationale is mechanistic and untested.
Evidence
Clinical: at least one published human trial or an approved drug
- Triptorelin pamoate monthly versus leuprolide in men with advanced prostate cancer: comparable castration rates (Heyns et al., 2003); the label reports castration by day 29 in 91.2% on 3.75 mg
- Single-arm phase 3 study of the 6-month 22.5 mg depot in locally advanced and metastatic prostate cancer (Lundström et al., 2009)
- Triptorelin 22.5 mg every 24 weeks in 44 children with central precocious puberty kept stimulated LH prepubertal in 93% or more at every visit (Klein et al., 2016)
- IV pharmacokinetics in healthy men and in renal or hepatic insufficiency (Müller et al., 1997)
- GnRH agonist trigger (triptorelin 0.2 mg) after ganirelix co-treatment in IVF (Fauser et al., 2002)
- Human-trial status: approved by the FDA as Trelstar (2000, prostate cancer) and Triptodur (2017, central precocious puberty), both marketed; no trial has tested a single dose for post-cycle recovery
References
- Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. Heyns CF, Simonin MP, Grosgurin P, et al., BJU International, 2003
- Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study. Lundström EA, Rencken RK, van Wyk JH, et al., Clinical Drug Investigation, 2009
- Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. Klein K, Yang J, Aisenberg J, et al., Journal of Pediatric Endocrinology & Metabolism, 2016
- Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency. Müller FO, Terblanchè J, Schall R, et al., British Journal of Clinical Pharmacology, 1997
- Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. Fauser BC, de Jong D, Olivennes F, et al., Journal of Clinical Endocrinology & Metabolism, 2002
Side effects
Trelstar label (men): hot flushes, skeletal pain, impotence or erectile dysfunction, headache, leg edema and testicular atrophy; an initial testosterone flare that can transiently worsen prostate cancer; hypersensitivity reactions, metabolic changes, cardiovascular disease, convulsions, severe skin reactions and QT prolongation. Triptodur label (children): injection-site reactions, vaginal bleeding after the first dose, hot flush, headache, psychiatric events, convulsions and pseudotumor cerebri. Long-term suppression lowers bone density.
Storage
- Storage
- Refrigerated (2-8°C)
- Lyophilized
- 24+ months at room temperature
- Reconstituted
- 28 days refrigerated
Pharmacology
- Half-life
- IV in healthy men: three phases of about 6 min, 45 min and 3 h (Trelstar label; Müller 1997). IM depot: peak at 1 to 3 h, release over 4, 12 or 24 weeks
- Bioavailability
- IM depot in men with prostate cancer: mean peak 28 to 44 ng/mL at 1 to 3 h, no accumulation over 9 to 12 months (Trelstar label). After 0.5 mg IV, 41.7% is excreted intact in urine. No SC bioavailability figure is published.
- Molecular weight
- 1311.45 Da
- Sequence
- pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2