Triptorelin (Trelstar / Triptodur / Decapeptyl / Diphereline)
Triptorelin pamoate; also available as triptorelin acetate. Chemical name: 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-tryptophyl-L-leucyl-L-arginyl-L-prolylglycine amide. Synonyms: triptoreline, D-Trp-6-LHRH, [D-Trp6]-GnRH.
Triptorelin is an FDA-approved synthetic GnRH superagonist decapeptide that produces medical castration through pituitary GnRH receptor downregulation, used for advanced prostate cancer and central precocious puberty. Ki approximately 0.3-1 nM at GnRHR-I (FDA label NDA 020715, 208956; DrugBank DB06825; PMC4813373).
Last updated: 2026-03-13
Safety Summary
Triptorelin's adverse effect profile is predominantly mechanism-related, driven by sustained suppression of gonadal sex steroids, and is shared across the GnRH agonist drug class. The FDA label includes warnings for: tumor flare (first 2-4 weeks), cardiovascular events with ADT, QT/QTc prolongation risk with co-administered QT-prolonging drugs, hyperglycemia/diabetes, and progressive bone loss. Rare serious events (SJS/TEN, seizures, pseudotumor cerebri) documented through post-marketing surveillance and updated in 2025 FDA label. A 2025 FAERS pharmacovigilance analysis (PMC12402341) identified neuropsychiatric/behavioral safety signals (hypothesis-generating, not causal). No evidence of tolerance/tachyphylaxis with chronic use. Immunogenicity appears low. No consistent de novo malignancy signal. No CYP-mediated drug interactions; interactions are pharmacodynamic (QT-prolonging drugs, other GnRH agonists, antidiabetics). Pediatric BMD effects are predominantly reversible after discontinuation.
Known Side Effects
very common (>50-70%)
common
common
common (>10% in ADT cohorts)
common
common
common (with chronic use)
uncommon
common
common (first dose)
common
uncommon (approximately 2-5%)
rare
rare
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rare
Who Should NOT Use This
Absolute contraindication per all formulation labels. Risk of anaphylaxis (FDA label; EMA SmPC).
Potential fetal harm from sex-steroid suppression. Animal reproductive toxicity findings. Counsel on contraception (FDA label; Canadian product monograph).
Not recommended; unknown excretion in breast milk (Canadian product monograph).
GnRH agonist therapy accelerates BMD loss. Baseline DXA and bone-protective measures recommended (Cancer Care Ontario monograph; FDA label).
Androgen/estrogen suppression alters insulin sensitivity. Monitor and adjust antidiabetic medications (Drugs.com; LiverTox).
Increased cardiovascular risk with ADT; additive QT/QTc prolongation risk with co-administered QT-prolonging drugs. Baseline ECG recommended (FDA label).
Risk of emotional lability, depression, and rare psychiatric events. Monitor mood (FDA label; EMA SmPC; FAERS PMC12402341).
Initial testosterone surge can worsen symptoms (urinary obstruction, spinal cord compression). Consider anti-androgen co-administration during flare period (FDA label).
Overlapping suppression without additional benefit. Not recommended (DrugBank DB06825; EMA SmPC).
Talk to Your Doctor
Before considering Triptorelin (Trelstar / Triptodur / Decapeptyl / Diphereline), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-11]
Evidence Assessment
FDA-approved with multiple active NDAs: TRELSTAR (NDA 020715, approved June 15, 2000) for advanced prostate cancer in three depot strengths, and TRIPTODUR (NDA 208956, approved June 29, 2017) for central precocious puberty. Labels updated through 2025. EMA-authorized via national procedures. TGA-registered (ARTG 219857), Health Canada-approved (DIN 02389282). Supported by pivotal Phase 3 programs (approximately 592 pooled patients for prostate cancer), pediatric Phase 3 (n=66 for CPP), and decades of clinical use worldwide.
1FDA Medical Review -- Triptorelin Pamoate 22.5 mg NDA 022437 (Pivotal Pooled Analysis)
FDA/CDER reviewers - FDA NDA Medical Review (2010) - Pooled Phase 3 analysis (regulatory submission) - ~592 pooled across DEB-96-TRI-01, DEB-TRI6M-301 and related studies
Approximately 93.3% of patients maintained castrate testosterone levels during treatment with depot triptorelin formulations.
Limitations: Pooled from open-label and single-arm elements; individual CIs not presented.
2Effectiveness, pharmacokinetics, and safety of triptorelin acetate microspheres in patients with locally advanced and metastatic prostate cancer
Wu G, Zhou F, Wang H, et al. - Therapeutic Advances in Medical Oncology (SAGE) (2024) - Open-label, single-arm, multicenter (ChiCTR2000033188) - 125
97.6% achieved testosterone <0.5 ng/mL at day 28 with maintenance through day 84.
Limitations: Single-arm; no comparator.
3Phase 3 Open-Label Trial of Triptorelin 6-Month Formulation in Chinese Children with Central Precocious PubertyNCT05029622
Not specified in raw data - Advances in Therapy (Springer) (2024) - Phase 3, open-label, single-arm - 66
100% LH suppression at month 6; 98.5% maintained at 12 months. Well tolerated, no severe AEs.
Limitations: Single-arm; Chinese pediatric population.
4Triptorelin and Radiation Therapy in Treating Patients Who Have Undergone Surgery for Intermediate-Risk Prostate CancerNCT00667069
Academic consortium - ClinicalTrials.gov (2008) - Phase 3 RCT - 424
Primary completion April 2020; results not yet posted publicly.
Limitations: Results pending publication.
5Randomized Double-Blinded Dose Escalation Trial of Triptorelin for Ovary Protection in Childhood-Onset SLE
Not specified in raw data - Arthritis & Rheumatology (2015) - Randomized, double-blind, placebo-controlled dose-escalation - 31
At 120 mcg/kg every 4 weeks, complete ovarian suppression in approximately 90% by day 22.
Limitations: Small sample; dose-finding study.
6Characterization of 12 GnRH peptide agonists -- a kinetic perspective
Nederpelt I et al. - British Journal of Pharmacology (2016) - In vitro binding/kinetic study - N/A (in vitro)
Triptorelin Ki approximately 1 nM at GnRHR-I. Full agonist with superagonist profile.
Limitations: In vitro only.
7An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer
Not specified - PMC Review (2016) - Narrative review - N/A
Comprehensive review confirming high-quality evidence for sustained testosterone suppression.
Limitations: Narrative review.
8Triptorelin associated adverse events evaluated using FAERS pharmacovigilance data
Not specified - Scientific Reports / PLOS One (2025) - Pharmacovigilance disproportionality analysis (FAERS) - N/A (post-marketing database)
Identified neuropsychiatric/behavioral safety signals. No consistent cancer signal. Overall consistent with GnRH agonist class.
Limitations: FAERS analyses cannot establish causality; subject to reporting bias.
9Head-to-head comparison of GnRH agonists in prostate cancer
Shim et al. - Investigative and Clinical Urology (2019) - Comparative clinical analysis - Not specified
Triptorelin produces deeper/more sustained testosterone suppression than leuprolide and goserelin.
Limitations: Specific design details not available.
10Triptorelin 6-month formulation in the management of prostate cancerPMID 19888782
Not specified - Not specified (2009) - Phase 3, open-label, multicenter - Not specified
Supported regulatory approval of 6-month depot formulation.
Limitations: Non-comparative; open-label.
11Cost-Effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in Metastatic Prostate CancerPMID 38663058
Not specified - Value in Health Regional Issues (2024) - Cost-effectiveness / pharmacoeconomic modeling - N/A (modeling)
Triptorelin intermediate cost/efficacy; practical choice balances potency, dosing frequency, and cost.
Limitations: Modeling study.