Overview
Triptorelin is a synthetic decapeptide and potent gonadotropin-releasing hormone (GnRH) agonist used to treat a variety of hormone-sensitive conditions. First patented in 1975 and approved for medical use in 1986, triptorelin has become one of the most widely prescribed GnRH agonists worldwide.
Unlike the native GnRH hormone, which stimulates reproductive hormone production, continuous triptorelin administration paradoxically suppresses the reproductive axis through receptor downregulation—a phenomenon that forms the basis of its therapeutic applications.
Triptorelin is included on the World Health Organization's List of Essential Medicines, reflecting its established role in treating conditions ranging from advanced prostate cancer to precocious puberty.
Triptorelin at a Glance
| Property | Value |
|---|---|
| Drug Class | GnRH agonist (LHRH agonist) |
| Amino Acid Sequence | pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 |
| Molecular Weight | 1,311.5 Da |
| Brand Names | Trelstar, Decapeptyl, Gonapeptyl, Triptodur, Diphereline |
| Administration | Intramuscular or subcutaneous injection |
| Formulations | 1-month, 3-month, and 6-month depot injections |
| FDA Status | Approved |
| WHO Essential Medicine | Yes |
How Triptorelin Works
Mechanism of Action
Triptorelin's mechanism relies on a biological paradox: while it initially stimulates the pituitary gland, continuous administration leads to profound suppression of reproductive hormones.
Phase 1: Initial Stimulation (Days 1-14)
When first administered, triptorelin binds to GnRH receptors in the anterior pituitary gland, triggering the release of:
- Luteinizing hormone (LH)
- Follicle-stimulating hormone (FSH)
This causes a temporary surge in downstream sex hormones—testosterone in men, estrogen in women. This "flare" effect can temporarily worsen hormone-sensitive conditions.
Phase 2: Receptor Downregulation (Weeks 2-4)
With continuous exposure, the pituitary GnRH receptors become desensitized and downregulated. The result:
- LH and FSH secretion drops dramatically
- Testosterone falls to castrate levels (<50 ng/dL)
- Estrogen decreases to postmenopausal levels
Phase 3: Sustained Suppression (Ongoing)
After 3-4 weeks, triptorelin maintains a state of "chemical castration" (in men) or "medical menopause" (in women) for as long as treatment continues.
Receptor Binding Affinity
Triptorelin has approximately 100-fold greater affinity for the GnRH receptor compared to endogenous GnRH. In comparative studies, triptorelin was six times more active than leuprolide in receptor binding assays.
This high receptor affinity contributes to triptorelin's effectiveness and may explain why some studies show it achieves deeper testosterone suppression than other GnRH agonists.
FDA-Approved Uses
Triptorelin has received FDA approval for several indications across different patient populations.
1. Advanced Prostate Cancer
Triptorelin (marketed as Trelstar) is approved for palliative treatment of advanced prostate cancer in adult men.
Why it works: Prostate cancer cells typically require testosterone to grow. By suppressing testosterone to castrate levels, triptorelin slows or stops tumor progression.
Efficacy data:
- Achieves castrate testosterone levels (<50 ng/dL) in >90% of patients within 4 weeks
- In head-to-head studies, triptorelin achieved the lowest mean testosterone levels compared to leuprolide and goserelin
- 93.2% of patients reached ultra-low testosterone (<10 ng/dL), compared to 86.4% with leuprolide
Note: Triptorelin is used for palliation—it manages the disease but does not cure it. It is typically part of androgen deprivation therapy (ADT), sometimes combined with anti-androgens or other treatments.
2. Central Precocious Puberty
Triptorelin (marketed as Triptodur) is FDA-approved to treat central precocious puberty (CPP) in children aged 2 years and older.
Why it works: CPP occurs when the hypothalamic-pituitary-gonadal axis activates too early, causing premature sexual development. Triptorelin suppresses this axis, halting pubertal progression until an appropriate age.
Dosing for CPP:
| Body Weight | Dose | Frequency |
|---|---|---|
| ≥30 kg | 22.5 mg | Every 24 weeks |
| 20-30 kg | 7.5 mg | Every 12 weeks |
| <20 kg | 3.75 mg | Every 12 weeks |
3. Endometriosis
Triptorelin (Decapeptyl) is approved for management of endometriosis.
Why it works: Endometriotic implants are estrogen-dependent. By inducing a hypoestrogenic state (similar to menopause), triptorelin causes the implants to shrink, reducing pain and other symptoms.
Treatment duration: Typically limited to 6 months due to bone density concerns with prolonged estrogen suppression.
4. Uterine Fibroids
Triptorelin is approved for preoperative treatment of uterine fibroids to reduce their size before surgery.
Benefits:
- Shrinks fibroids, making surgery easier
- Reduces intraoperative blood loss
- May allow less invasive surgical approaches
Treatment duration: Usually 3-4 months before planned surgery.
Off-Label Uses
Beyond FDA-approved indications, triptorelin is used off-label for several conditions.
Gender-Affirming Care
Triptorelin is used as a puberty blocker in transgender adolescents experiencing gender dysphoria. It suppresses the development of secondary sex characteristics, providing time for psychological evaluation and decision-making.
The "Dutch Protocol," first published in 1998 by Drs. Cohen-Kettenis and van Goozen, established the use of GnRH agonists like triptorelin in gender-affirming care. This approach has been incorporated into WPATH and Endocrine Society guidelines.
Breast Cancer
In the European Union, triptorelin is approved for adjuvant treatment of hormone receptor-positive early-stage breast cancer in premenopausal women, typically combined with tamoxifen or aromatase inhibitors.
Male Hypersexuality
Triptorelin may be used to treat severe male hypersexuality or paraphilias where testosterone suppression is clinically indicated.
Assisted Reproduction
In IVF protocols, triptorelin may be used to prevent premature ovulation by suppressing the LH surge, allowing controlled timing of egg retrieval.
Available Formulations
Triptorelin comes in extended-release depot formulations, reducing injection frequency:
| Formulation | Dose | Frequency | Brand Names |
|---|---|---|---|
| Monthly | 3.75 mg | Every 4 weeks | Trelstar, Decapeptyl |
| Quarterly | 11.25 mg | Every 12 weeks | Trelstar LA, Decapeptyl SR |
| Semi-annual | 22.5 mg | Every 24 weeks | Trelstar, Triptodur |
All formulations are administered by healthcare providers via intramuscular or subcutaneous injection.
Side Effects
Triptorelin's side effects largely stem from its intended pharmacological effect—suppression of sex hormones.
Very Common Side Effects (>10% of patients)
| Side Effect | Frequency | Notes |
|---|---|---|
| Hot flashes | 70-87% | Most common; due to hormone suppression |
| Injection site reactions | Variable | Pain, redness, swelling at injection site |
| Decreased libido | Common | Expected with testosterone/estrogen suppression |
| Erectile dysfunction | Common (men) | Due to testosterone suppression |
| Headache | Common | Usually transient |
Common Side Effects (1-10%)
- Fatigue
- Weight changes
- Mood changes
- Sleep disturbances
- Skeletal pain
- Nausea
- Dizziness
- Leg pain
- Gynecomastia (breast tissue growth in men)
Initial Flare Reaction
During the first 2 weeks, the initial hormone surge can cause a "flare reaction":
- In prostate cancer: Temporary worsening of symptoms including bone pain, urinary obstruction, or spinal cord compression
- In endometriosis: Brief increase in pelvic pain
To mitigate the flare, physicians may co-prescribe anti-androgens (in men) during the initial treatment phase.
Long-Term Concerns
Bone Density Loss: Prolonged estrogen or testosterone suppression leads to decreased bone mineral density. Monitoring and interventions (calcium, vitamin D, bisphosphonates) may be needed.
Cardiovascular Risk: GnRH agonist use in men is associated with increased risk of myocardial infarction, stroke, and sudden cardiac death. Risk factors should be evaluated before treatment.
Metabolic Changes: Androgen deprivation can cause:
- Reduced insulin sensitivity
- Increased body fat
- Dyslipidemia
- Higher diabetes risk
QTc Prolongation: Triptorelin may prolong the QT interval, requiring caution in patients with cardiac conditions or those taking other QT-prolonging drugs.
Contraindications and Warnings
Absolute Contraindications
- Hypersensitivity to triptorelin, other GnRH agonists, or any component
- Pregnancy (Category X) — can cause fetal harm
- Concurrent use with QT-prolonging drugs (amiodarone, dofetilide, etc.) requires careful evaluation
Warnings and Precautions
| Condition | Concern |
|---|---|
| Cardiovascular disease | Increased MI, stroke risk |
| Diabetes/prediabetes | May worsen glucose tolerance |
| Seizure history | Reports of convulsions with GnRH agonists |
| Depression/psychiatric conditions | May worsen; monitor closely |
| Osteoporosis risk | Long-term use decreases bone density |
| QT prolongation | ECG monitoring recommended in at-risk patients |
Pediatric Warning: Pseudotumor Cerebri
In children receiving GnRH agonists, pseudotumor cerebri (intracranial hypertension) has been reported. Symptoms include headache, visual disturbances, nausea, and vomiting.
Drug Interactions
Triptorelin has 283 known drug interactions, primarily related to QTc prolongation:
Major Interactions (Avoid Combination):
- Amiodarone
- Dofetilide
- Sotalol
- Dronedarone
- Other Class III antiarrhythmics
Moderate Interactions (Use Caution):
- Antipsychotics (some prolong QT)
- Certain antidepressants (TCAs, some SSRIs)
- Fluoroquinolone antibiotics
- Methadone
Additional Consideration: Hyperprolactinemic drugs should be avoided, as elevated prolactin reduces pituitary GnRH receptor numbers, potentially diminishing triptorelin's effectiveness.
Triptorelin vs. Other GnRH Agonists
Several GnRH agonists are available for similar indications. How does triptorelin compare?
Comparison Table
| Feature | Triptorelin | Leuprolide | Goserelin |
|---|---|---|---|
| Receptor Affinity | Highest (100x GnRH) | High (50x GnRH) | High (50x GnRH) |
| Testosterone <10 ng/dL | 93.2% | 86.4% | 54.2% |
| Formulations | 1, 3, 6 month | 1, 3, 4, 6 month | 1, 3 month |
| Administration | IM or SC injection | IM or SC injection | SC implant |
| Half-life | 2.8 hours | 3 hours | 4.9 hours |
Key Differences
Testosterone Suppression: In a direct comparison study, triptorelin achieved significantly deeper testosterone suppression than both leuprolide and goserelin. At the ultra-low threshold of <10 ng/dL, triptorelin was superior (93.2% vs. 86.4% vs. 54.2%).
Clinical Equivalence: At the standard castration threshold of <50 ng/dL, all three agents show similar efficacy (~97-99% achieve castration).
Receptor Binding: Triptorelin has the highest in vitro receptor binding affinity among the GnRH agonists, which may contribute to its deeper suppression.
Convenience: All three offer extended-release formulations. Goserelin uses a subcutaneous implant, while triptorelin and leuprolide are reconstituted injections.
Administration and Monitoring
How Triptorelin Is Given
Triptorelin is administered exclusively by healthcare providers:
- Reconstitution: The lyophilized powder is mixed with the provided diluent
- Injection: Given intramuscularly (into muscle) or subcutaneously (under skin)
- Site rotation: Injection sites should be rotated to minimize reactions
Important: Triptorelin must be administered by a healthcare provider—it is not a self-administered medication.
Monitoring Requirements
| Parameter | Frequency | Purpose |
|---|---|---|
| Testosterone (men) | Periodic | Confirm suppression to <50 ng/dL |
| PSA (prostate cancer) | Periodic | Monitor treatment response |
| Bone density (DEXA) | Annually (long-term use) | Detect bone loss |
| Blood glucose | Periodic | Monitor metabolic effects |
| Signs of flare | First 2 weeks | Detect worsening symptoms |
Frequently Asked Questions
How quickly does triptorelin work?
Triptorelin begins suppressing hormones within 2-4 weeks of the first injection. However, during the first 1-2 weeks, hormone levels temporarily increase (the "flare" effect) before dropping to suppressed levels.
Is triptorelin reversible?
For most patients, hormone suppression reverses after stopping triptorelin. However, the timeline varies:
- Testosterone recovery (men): Typically 3-6 months, but may take longer with extended use
- Fertility: May be temporarily affected; recovery is generally expected but not guaranteed
What is the difference between triptorelin and leuprolide?
Both are GnRH agonists with similar mechanisms. Key differences:
- Triptorelin has higher receptor binding affinity
- Triptorelin achieves deeper testosterone suppression in comparative studies
- Clinical outcomes at standard thresholds are similar
- Cost and availability may vary by region
Can triptorelin be used long-term?
Triptorelin can be used long-term (years) for conditions like prostate cancer. However, extended use requires monitoring for:
- Bone density loss
- Cardiovascular health
- Metabolic changes
- Psychiatric symptoms
For endometriosis, treatment is typically limited to 6 months due to bone health concerns.
Does triptorelin cause weight gain?
Weight gain is a recognized side effect, particularly in men undergoing androgen deprivation. The hormonal changes affect body composition, typically increasing fat mass while decreasing muscle mass.
What happens if I miss a dose?
Contact your healthcare provider immediately if you miss a scheduled injection. The timing is important for maintaining hormone suppression—gaps in treatment can allow hormones to recover, potentially affecting disease control.
Summary
Triptorelin is a potent GnRH agonist that paradoxically suppresses reproductive hormones through continuous administration. Its FDA-approved uses include:
- Prostate cancer (palliative treatment in advanced disease)
- Central precocious puberty (children ≥2 years)
- Endometriosis (symptom management)
- Uterine fibroids (preoperative size reduction)
Key characteristics:
- Achieves chemical castration within 3-4 weeks
- Highest receptor binding affinity among GnRH agonists
- Available in convenient 1, 3, and 6-month depot formulations
- Well-established safety profile with predictable side effects
- Listed on WHO Essential Medicines
While triptorelin is highly effective for its approved indications, patients and providers should weigh the benefits against the side effects of long-term hormone suppression, including hot flashes, bone density loss, cardiovascular risks, and metabolic changes.
References
- Triptorelin. Wikipedia. Available at: https://en.wikipedia.org/wiki/Triptorelin
- Triptorelin. LiverTox - NCBI Bookshelf. Available at: https://www.ncbi.nlm.nih.gov/books/NBK548756/
- Triptorelin. DrugBank. Available at: https://go.drugbank.com/drugs/DB06825
- Crawford ED, et al. Effectiveness of three different LHRH agonists in prostate cancer. PMC. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6607074/
- Bolton EM, et al. Are all GnRH agonists equivalent for prostate cancer? BJU International. Available at: https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14168
- Cleveland Clinic. Triptorelin Injection: Prostate Cancer Treatment. Available at: https://my.clevelandclinic.org/health/drugs/19231-triptorelin-injection-prostate-cancer
- Mayo Clinic. Triptorelin (intramuscular route). Available at: https://www.mayoclinic.org/drugs-supplements/triptorelin-intramuscular-route/side-effects/drg-20066536
- Drugs.com. Triptorelin Uses, Dosage, Side Effects. Available at: https://www.drugs.com/triptorelin.html
- FDA Prescribing Information. TRELSTAR (triptorelin pamoate). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020715s040,021288s035,022427s015lbl.pdf
- Hembree WC, et al. Medical interventions in transgender youth. Endotext - NCBI Bookshelf. Available at: https://www.ncbi.nlm.nih.gov/books/NBK577212/
This article is for educational purposes only. Triptorelin is a prescription medication that should only be used under the supervision of a qualified healthcare provider. Always consult with your physician before starting or stopping any medication.