Triptorelin

Triptorelin is a synthetic decapeptide gonadotropin-releasing hormone (GnRH) agonist analog that was developed at Tulane University in Andrew V. Schally's laboratory and patented in 1975. It received FDA approval in 1986 and appears on the WHO Model List of Essential Medicines. The drug operates through a characteristic biphasic mechanism: initially stimulating the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary, followed by sustained receptor downregulation that suppresses gonadotropin secretion, resulting in chemical castration within 3-4 weeks of continuous administration. This reversible suppression of the hypothalamus-pituitary-gonadal (HPG) axis makes triptorelin a first-line treatment for advanced prostate cancer, central precocious puberty, endometriosis, and uterine fibroids. It is also widely used in assisted reproductive technology to prevent premature ovulation during IVF cycles. Available in multiple sustained-release formulations (1-month, 3-month, and 6-month depot injections), triptorelin can be administered intramuscularly or subcutaneously. The medication is available by prescription globally and is marketed in over 80 countries for various hormone-dependent conditions.

Primary Therapeutic Applications

Prostate Cancer

• Excellent castration rates: Achieves castrate testosterone levels (<50 ng/dl) in 97.5% of patients within 28 days, maintaining suppression in 98.3% at 12 months^[1]
• Substantial PSA reduction: Clinical trials demonstrate median PSA decline from 46.8 ng/ml at baseline to 1.3 ng/ml at 9 months, with 96-97% reduction maintained long-term^[1]
• Superior survival outcomes: In a 284-patient randomized trial, triptorelin was associated with significantly higher 9-month survival rate compared to leuprolide (97.0% vs 90.5%)^[1]
• Sustained efficacy: Real-world evidence from 1,241 men showed mean PSA reduction from 117.9 ng/ml to 16.6 ng/ml after 12 months^[1]
• Long-term effectiveness: Italian database studies demonstrate long survival and treatment duration in prostate cancer patients^[2]

Central Precocious Puberty

• Complete hormonal suppression: Achieves 100% LH suppression (peak <3 IU/L) in all patients at 3, 6, and 12 months, with LH decreasing from 25.7 IU/L to 0.9 IU/L^[3]
• Improved final height: Girls gain 4.8 cm compared to predicted height before treatment and 8.3 cm versus historical controls; boys show 13.7 cm improvement^[4]
• High success rates: Meta-analysis of 153 children found 87.6% achieved suppressed LH at 3 months and 92.8% at 6 months^[4]
• Pubertal regression: Treatment leads to reversal of secondary sexual characteristics, with breast development regression and uterine size reduction^[3]
• Preserved fertility: The PREFER study found only 1.7% infertility rate in women treated during childhood, with 84.4% achieving pregnancy within 12 months of trying^[5]

Endometriosis

• Effective pain relief: Pain-related symptoms decreased in all patients after 8 weeks of treatment, with laparoscopic assessment showing reduction in rAFS scores in 84% of cases^[6]
• Chemical castration: Over 98% of patients achieve chemical castration by week 12, effectively reducing estrogen-driven endometrial growth^[7]
• Comparable efficacy to alternatives: Demonstrated equal effectiveness to danazol in reducing endometriotic implants (58% vs 51% reduction)^[8]
• Noninferior formulations: The 3-month formulation proved noninferior to monthly injections in a 300-patient Chinese trial^[7]

Uterine Fibroids

• Significant volume reduction: Uterine volumes decrease by 45.0% and fibroid volumes by 68.0% after three months of treatment^[9]
• Pre-surgical benefit: Valuable for shrinking large fibroids prior to hysterectomy or myomectomy^[9]
• Long-term success in perimenopausal women: Definitely beneficial in perimenopausal women and nearly half of premenopausal women, in whom hysterectomy can be prevented^[9]

Assisted Reproductive Technology (IVF)

• Prevents premature ovulation: Daily administration of 15 μg triptorelin is sufficient to prevent premature LH surge during controlled ovarian hyperstimulation^[10]
• Enables controlled cycles: Controls ovarian function in ovarian stimulation cycles by inhibiting the LH peak, preventing spontaneous ovulation^[10]
• Safe pregnancy outcomes: Pregnancy outcome is not adversely affected by GnRH agonist administration during the luteal phase of conception cycles^[10]

Additional Benefits

Polycystic Ovary Syndrome (PCOS)

• Hormone normalization: Can normalize dysregulated LH and FSH levels characteristic of PCOS^[11]
• Androgen reduction: Indirectly dampens ovarian androgen production, including testosterone^[11]
• Ovulation restoration: May help restore ovulatory function disrupted by the syndrome^[11]

Fertility Preservation

• Chemotherapy protection: Can obtain menstrual suppression in postpubertal females receiving chemotherapy, decreasing hemorrhage risk from thrombocytopenia^[10]
• No negative long-term impact: Does not negatively impact women's fertility in adulthood when used to treat childhood precocious puberty^[5]

Clinical Safety Profile

Common Side Effects

• Androgen deprivation effects: Hot flushes occur in 50-58.6% of patients, representing the most common side effect^[1][12]
• Sexual dysfunction: Erectile dysfunction (4-7.1%), decreased libido (3%), and impotence are expected pharmacological outcomes^[1][12]
• Injection site reactions: Injection site pain reported in some patients, though generally well-tolerated^[12]
• General symptoms: Skeletal pain (12.1%), headache (5-22%), fatigue, hypertension, dizziness, insomnia, and emotional lability^[3][12]
• Gastrointestinal effects: Nausea, diarrhea, vomiting, and weight gain may occur^[12]
• Pediatric tolerability: In children, mild side effects include headache (22%), hot flushes (1%), and occasional light vaginal bleeding (4 events in 3 girls)^[3]

Serious Warnings and Adverse Events

Initial Tumor Flare: Triptorelin causes a temporary hormone surge when first started or after each new injection, which can worsen prostate cancer symptoms including urethral obstruction, bladder outlet obstruction, bone pain, spinal cord injury, and hematuria in early treatment stages^[12]

Spinal Cord Compression: Cases of spinal cord compression have been reported with GnRH agonists, which may contribute to weakness or paralysis with or without fatal complications^[12]

Mental Health Effects: Some patients experience new or worsening mental problems including abnormal crying, aggression, agitation, delusions, irritability, nervousness, or restlessness^[12]

Seizures: New or worsening seizures (convulsions) have been reported in some patients^[12]

Pseudotumor Cerebri: Reports of idiopathic intracranial hypertension have been observed in pediatric patients receiving GnRH agonists including triptorelin^[12]

Anaphylaxis: Serious allergic reactions including life-threatening anaphylaxis can occur and require immediate medical attention^[12]

Metabolic and Cardiovascular Concerns

Diabetes Risk: Hyperglycemia and increased risk of developing diabetes have been reported in men receiving GnRH agonists^[12]

Metabolic Changes: May cause long-term metabolic changes leading to hyperlipidemia and non-alcoholic liver disease^[12]

QTc Prolongation: Has serious interactions with at least 47 drugs and moderate interactions with 78 drugs, many related to QTc interval prolongation that can increase risk of dangerous heart rhythm abnormalities^[12]

Hepatic Safety

Low hepatotoxicity: Carries a likelihood score of "E" (unlikely cause of clinically apparent liver injury)^[13]

Minor enzyme elevations: Occur in 2-5% of patients but rarely exceed three times upper limit of normal and are usually mild, asymptomatic, and resolve without dose modification^[13]

No acute liver injury: Not definitively linked to acute liver injury with jaundice; no cases attributed to triptorelin in Iceland or US prospective drug-induced liver injury registries^[13]

Regulatory Status

FDA Approval: Approved in 1986; Triptodur approved June 29, 2017 for central precocious puberty in children aged 2 years and older^[14]

WHO Recognition: Appears on the WHO Model List of Essential Medicines^[15]

Global Availability: Marketed in over 80 countries for prostate cancer, endometriosis, fibromyoma, breast cancer, and precocious puberty^[14]

Prescription Status: Available by prescription in the United States, Canada, and Australia (Schedule 4)^[15]

Contraindications

Allergy: Contraindicated in patients allergic to triptorelin or similar GnRH agonists such as leuprolide (Lupron, Viadur, Eligard) or goserelin (Zoladex)^[12]

Pregnancy: Classified as Pregnancy Category X and contraindicated in pregnant women or women who may become pregnant; could harm unborn baby^[12]

Important Safety Considerations

Discontinuation rates: Despite side effects, discontinuation rates remain low across clinical trials^[1]

Reversibility: Effects are reversible; the pituitary-gonadal axis recovers adequately after treatment discontinuation^[4]

No long-term reproductive harm: No long-term adverse events on reproductive function have been reported, with fertility preserved in women treated during childhood^[5]

Route flexibility: Similar pharmacokinetic parameters between intramuscular and subcutaneous routes, allowing administration flexibility^[1]