Triptorelin (Trelstar) - GnRH Agonist for Advanced Prostate Cancer — Reproduction
FDA-approved GnRH agonist for palliative treatment of advanced prostate cancer via sustained testosterone suppression.
Overview
Triptorelin pamoate (Trelstar) is a synthetic decapeptide GnRH agonist FDA-approved in 2000 for palliative treatment of advanced prostate cancer. Available in 1-month (3.75 mg), 3-month (11.25 mg), and 6-month (22.5 mg) depot formulations. Phase 3 trials showed 97.5% achieved castrate testosterone (≤50 ng/dL) from week 5 onwards, with mean suppression to 15.4 ng/dL by week 4. Comparable efficacy to leuprolide and goserelin for androgen deprivation therapy. Mechanism: initial GnRH receptor activation → testosterone flare, followed by receptor downregulation → sustained LH/FSH suppression → medical castration. Same ADT side effects profile: hot flashes (70%), bone loss, metabolic syndrome, cardiovascular risks, sexual dysfunction. Requires antiandrogen co-treatment for first 4 weeks to prevent testosterone flare complications.
Indications
- Advanced prostate cancer (palliative androgen deprivation therapy)
- Metastatic prostate cancer
- Gender-affirming hormone therapy (off-label, feminizing regimens)
Mechanism of Action
Testosterone-dependent tumor growth in advanced/metastatic disease
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Triptorelin pamoate 3.75 mg depot | 3.75 mg IM | Every 4 weeks (monthly) | Deep IM injection (gluteal or deltoid); add bicalutamide 50 mg daily for first 4 weeks |
| Triptorelin pamoate 11.25 mg depot | 11.25 mg IM | Every 12 weeks (quarterly) | Reduces injection frequency; add antiandrogen for first dose |
| Triptorelin pamoate 22.5 mg depot | 22.5 mg IM | Every 24 weeks (semi-annually) | Only 2 injections/year; convenient for long-term ADT |
Evidence Grade
GRADE A
Safety & Contraindications
- ⚠️ PRESCRIPTION MEDICATION - Oncology supervision required
- TESTOSTERONE FLARE: First 2-3 weeks may worsen symptoms (bone pain, urinary obstruction, spinal cord compression) - MUST add antiandrogen (bicalutamide 50 mg daily) for first 4 weeks
- Cardiovascular risks: Long-term ADT increases MI, stroke, sudden cardiac death risk
- Metabolic syndrome: Weight gain, insulin resistance, dyslipidemia, new-onset diabetes
- Bone loss: Significant osteoporosis risk with chronic use - DEXA screening, calcium/vitamin D supplementation, consider bisphosphonates
- Hot flashes (70%): Most common side effect; may use low-dose estrogen patch or venlafaxine
- Sexual dysfunction: Erectile dysfunction and loss of libido (expected effect of medical castration)
- Depression, fatigue, cognitive changes: Common with prolonged ADT
- Anemia: Mild normocytic anemia develops in ~10%
- Injection site reactions: Pain, induration at IM injection site