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Triptorelin
Triptorelin
Triptorelin
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Triptorelin
Clinical data
Trade namesDecapeptyl, others
AHFS/Drugs.comMicromedex Detailed Consumer Information
License data
Routes of
administration		Intramuscular
Drug classGnRH analogue; GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-lifeThe elimination half-life for patients with hepatic impairment was similar to that of patients with renal impairment (geometric mean t(1/2, z): 6.6 h, 7.7 h and 7.6 h for Groups II, III and IV, respectively), but significantly longer than in healthy volunteers (2.8 h for Group I)

[3]

Triptorelin is a gonadotropin-releasing hormone (GnRH) analogue with enhanced affinity for GnRH receptors and a prolonged half-life due to its resistance to enzymatic degradation.
ExcretionKidney
Identifiers
  • 5-oxo-D-prolyl-L-histidyl-Ltryptophyl-L-seryl-Ltyrosyl-3-(1H-indol-2-yl)-L-alanylleucyl-L-arginyl-L-prolylglycinamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.165.044 Edit this at Wikidata
Chemical and physical data
FormulaC64H82N18O13
Molar mass1311.473 g·mol−1
3D model (JSmol)
  • CC(C)C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N)NC(=O)[C@@H](Cc2c[nH]c3c2cccc3)NC(=O)[C@H](Cc4ccc(cc4)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc5c[nH]c6c5cccc6)NC(=O)[C@H](Cc7cnc[nH]7)NC(=O)[C@@H]8CCC(=O)N8
  • InChI=1S/C64H82N18O13/c1-34(2)23-46(56(88)75-45(13-7-21-69-64(66)67)63(95)82-22-8-14-52(82)62(94)72-31-53(65)85)76-58(90)48(25-36-28-70-42-11-5-3-9-40(36)42)78-57(89)47(24-35-15-17-39(84)18-16-35)77-61(93)51(32-83)81-59(91)49(26-37-29-71-43-12-6-4-10-41(37)43)79-60(92)50(27-38-30-68-33-73-38)80-55(87)44-19-20-54(86)74-44/h3-6,9-12,15-18,28-30,33-34,44-52,70-71,83-84H,7-8,13-14,19-27,31-32H2,1-2H3,(H2,65,85)(H,68,73)(H,72,94)(H,74,86)(H,75,88)(H,76,90)(H,77,93)(H,78,89)(H,79,92)(H,80,87)(H,81,91)(H4,66,67,69)/t44-,45-,46-,47-,48+,49-,50-,51-,52-/m0/s1 ☒N
  • Key:VXKHXGOKWPXYNA-PGBVPBMZSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).[4][5] It was patented in 1975 and approved for medical use in 1986.[6] Triptorelin is a therapeutic alternative on the World Health Organization's List of Essential Medicines.[7]

It is a decapeptide (pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2) and a gonadotropin-releasing hormone agonist (GnRH agonist) used as the acetate or pamoate salts.

Primary indications include endometriosis,[8] for the reduction of uterine fibroids, to treat prostate cancer, and to treat male hypersexuality with severe sexual deviation.[5] The drug has also been used off label to delay puberty in patients with gender dysphoria.[9]


Medical uses

[edit]
See also: Gonadotropin-releasing hormone agonist § Medical uses

Triptorelin is used to treat prostate cancer as part of androgen deprivation therapy.[10]

Another common use in the United Kingdom is for hormone replacement therapy to suppress testosterone or estrogen levels in transgender people (in conjunction with estradiol valerate for trans women or testosterone for trans men). Spironolactone and cyproterone acetate are other drugs used by trans people to suppress sex hormones, but these drugs have a completely different mechanism of action.[11] It can also be used as a puberty blocker[12] in the case of precocious puberty.[10]

Triptorelin has been used as a chemical castration agent for reducing sexual urges in sex offenders.[13]

Drug action

[edit]

Triptorelin is a gonadorelin analogue, also known as luteinizing hormone releasing analogue (GnRH analogue, LHRH analogue).[4] The drug binds to receptors in the pituitary gland and stimulates secretion of gonadotropins (namely luteinizing hormone LH and follicle-stimulating hormone FSH). This causes an initial phase of LH and FSH stimulation, prior to down-regulation of the gonadotrophin-releasing hormone receptors, thereby reducing the release of gonadotropins in the long term, which in turn leads to the inhibition of androgen and estrogen production.[5]

Side-effects

[edit]

General side effects can include:[5]

  • Anaphylaxis
  • Arthralgia
  • Asthenia
  • Asthma
  • Breast tenderness (males and females)
  • Changes in blood pressure
  • Changes in breast size
  • Depression
  • Ovarian cysts
  • Mood changes
  • Skin rashes
  • Hot flashes
  • Weight changes

Society and culture

[edit]

Brand names

[edit]

Triptorelin is marketed under the brand names Decapeptyl (Ipsen) for treating prostate cancer, endometriosis, uterine myomas, and precocious puberty,[14] and Diphereline and Gonapeptyl (Ferring Pharmaceuticals).[15] In the United States, it is sold by Watson Pharmaceuticals as Trelstar [16] and by Arbor Pharmaceuticals as Triptodur (an extended-release 6-month depot injection).[17] In Iran, triptorelin is marketed under the brand name Variopeptyl. In the UK and Germany, it is sold as Salvacyl for the treatment of sexual deviations.[18]

History

[edit]

Triptorelin was developed in Andrew V. Schally's lab at Tulane University.[19] Debiopharm licensed the drug from Tulane in 1982.[20]

Research

[edit]

Triptorelin and other antiandrogens may be effective in the treatment of obsessive–compulsive disorder.[21]

Dosage in IVF treatment

[edit]

Minimal daily dose of triptorelin acetate needed to suppress a premature LH surge during IVF treatment has been determined to be 15 microgram daily, and that 50 microg is equivalent to 100 microg in terms of IVF results.[22]

GnRHa doses used in IVF are derived from treatment

schedules used in disseminated prostate cancer, which aim at

complete gonadal suppression under all circumstances. Some

comparative studies indicate that the daily dose of agonist

used in IVF may be decreased without compromising the

results

The interval between initiation of study medication and start of FSH stimulation was defined as the desensitization phase.

For both parameters, adjacent comparisons showed a statistically significant difference between the effect of placebo and 15 μgtriptorelin, but not between 15 and 50 μg, or between 50 and100 μg (Table II).

moreover, it appeared that a daily dose of 50 μg triptorelincreates a state of pituitary desensitization comparable with the "standard" dose of 100 μg, and this endocrine finding was confirmed in the current study.

In prostate cancer

[edit]

Modern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T < 50 ng/dL

Pharmacokinetics

[edit]

Gonapeptyl Depot 3.75 mg

[edit]

The systemic bioavailability of the active component triptorelin from the intramuscular depot is 38.3% in the first 13 days (2.9% per day). Further release is linear at 0.92% of the dose per day on average (34μg). Bioavailability after S.C. application is 69% of I.M. availability.

Plasma triptorelin values decreased to approx. 100 pg/ml before the next application after I.M. or S.C. application (median values).

References

[edit]

Further reading

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Triptorelin

View on Grokipedia
from Grokipedia
Triptorelin is a synthetic decapeptide analog of (GnRH) that functions as a potent agonist, initially stimulating the release of (LH) and (FSH) before causing receptor downregulation and subsequent suppression of secretion, thereby reducing testosterone levels in men and levels in women. Primarily indicated for the palliative treatment of advanced through , it achieves castrate levels of testosterone, slowing cancer progression and alleviating symptoms such as . Triptorelin is also approved for treating central in children by delaying onset and reducing associated growth accelerations. Administered via intramuscular depot injections (e.g., as Trelstar or Decapeptyl) at intervals of 1, 3, or 6 months, it demonstrates sustained efficacy in maintaining hormone suppression, though initial flare-ups may require anti-androgen co-therapy to mitigate transient tumor stimulation. Common adverse effects include hot flashes, fatigue, and injection-site reactions, reflecting its impact on pathways.

Pharmacology

Mechanism of action

Triptorelin is a synthetic decapeptide analogue of (GnRH), functioning as a high-affinity agonist at GnRH receptors in the gland. Upon initial administration, triptorelin binds to these receptors and stimulates the release of (LH) and (FSH) from gonadotroph cells, mimicking the pulsatile action of endogenous GnRH and thereby inducing a transient surge in circulating gonadotropins. This acute phase elevates gonadal steroidogenesis, increasing testosterone levels in males and levels in females within hours to days, depending on the dose and formulation. With continuous or repeated dosing, triptorelin causes receptor desensitization through mechanisms including downregulation of GnRH receptor expression, internalization of receptor-ligand complexes, and uncoupling of pathways. These processes lead to a marked suppression of LH and FSH , typically achieving castrate levels of testosterone (below 50 ng/dL) in men after 2-4 weeks of therapy. In women, levels are similarly reduced to postmenopausal ranges. The net effect is profound inhibition of gonadal function, rendering triptorelin a potent suppressor of sex steroid production, which underpins its therapeutic applications in hormone-dependent conditions. This biphasic response—initial flare followed by downregulation—is characteristic of GnRH agonists and distinguishes them from antagonists, which lack the stimulatory phase.

Pharmacokinetics

Triptorelin exhibits a three-compartment pharmacokinetic profile following intravenous (IV) administration, characterized by rapid initial distribution and slower elimination phases. After a single IV bolus of 0.5 mg, the drug is completely absorbed, with distribution half-lives of approximately 6 minutes and 45 minutes, followed by an elimination of about 3 hours. Total clearance in healthy male volunteers is approximately 211.9 mL/min. For intramuscular (IM) depot formulations, such as triptorelin pamoate, absorption is sustained, with peak serum levels typically reached on days 2 to 4 post-injection. After the initial release phase, serum concentrations stabilize at mean levels of about 0.06 ng/mL for roughly 12 weeks following a single IM dose of triptorelin pamoate 3.75 mg. The volume of distribution remains consistent with IV data, reflecting distribution into extracellular fluids. Metabolism of triptorelin in humans is not fully characterized but does not involve cytochrome P450 enzymes, and no specific metabolites have been identified; the peptide is likely degraded enzymatically in tissues or plasma. Excretion occurs via both hepatic and renal routes, with the drug cleared completely through these pathways. In patients with moderate to severe renal or hepatic impairment, the area under the curve (AUC) for triptorelin increases by approximately twofold compared to healthy subjects, though distribution half-lives remain unchanged; dose adjustments may be necessary in such populations. The elimination half-life is generally 3 to 5 hours across formulations, unaffected by age or sex in adults.

Clinical uses

Prostate cancer

Triptorelin pamoate, marketed as Trelstar, is approved by the U.S. Food and Drug Administration for the palliative treatment of advanced prostate cancer in adult men. As a gonadotropin-releasing hormone (GnRH) agonist, it forms the basis of androgen deprivation therapy (ADT) by suppressing gonadal testosterone production to castrate levels (typically below 50 ng/dL or 1.7 nmol/L), thereby inhibiting the growth of androgen-dependent prostate tumors. Initial administration may cause a transient testosterone surge (flare), which can exacerbate symptoms in some patients; anti-androgens such as bicalutamide are often co-administered prophylactically for the first few weeks to mitigate this risk. Available formulations include intramuscular injections of 3.75 mg (monthly), 11.25 mg (every 3 months), and 22.5 mg (every 6 months), allowing flexibility based on patient needs and monitoring requirements. Clinical studies demonstrate that these sustained-release formulations achieve rapid and sustained testosterone suppression in over 95% of patients, with nadir levels often below 20 ng/dL, correlating with reductions in (PSA) levels and tumor progression delay. For instance, in phase III trials involving over 1,000 patients with advanced disease, triptorelin maintained castrate testosterone levels for the full dosing interval in 97-99% of cases, comparable to other GnRH agonists like leuprolide. Triptorelin is particularly suited for long-term ADT in locally advanced or metastatic hormone-sensitive , where it is often combined with or used as monotherapy when is not feasible. Pooled analyses from nine phase III studies (n=1,511) showed that deeper testosterone suppression (nadir <20 ng/dL) was associated with improved clinical outcomes, including longer time to PSA progression and reduced risk of skeletal events, independent of baseline prognostic factors. In real-world settings, it has also alleviated lower urinary tract symptoms (LUTS) in men with moderate-to-severe bother from prostate cancer-related obstruction, with significant improvements in International Prostate Symptom Scores observed within 3-6 months. Ongoing research explores triptorelin in neoadjuvant settings before prostatectomy or as part of intermittent ADT to potentially reduce cumulative toxicity while preserving efficacy, though definitive superiority over continuous therapy remains unproven. Patient selection emphasizes monitoring for breakthrough testosterone rises, which occur in <5% of cases and may necessitate dosage adjustments or switching agents. Overall, triptorelin's efficacy profile supports its role as a standard ADT option, with evidence from randomized controlled trials confirming non-inferiority to historical standards in delaying disease progression.

Precocious puberty

Triptorelin, a gonadotropin-releasing hormone (GnRH) agonist, is approved for treating central precocious puberty (CPP) in pediatric patients aged 2 years and older, where it suppresses premature activation of the hypothalamic-pituitary-gonadal axis to halt pubertal progression. The U.S. approved the 6-month prolonged-release formulation (Triptodur, 22.5 mg) in June 2017 as the first GnRH agonist dosed every 6 months for this indication, based on pharmacokinetic and pharmacodynamic data demonstrating sustained suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Clinical trials have confirmed triptorelin's efficacy in suppressing gonadal hormones, reducing bone age advancement, and improving predicted adult height in children with CPP. In a phase 3 open-label trial of the 6-month formulation in Chinese children, triptorelin suppressed stimulated LH levels below 4 IU/L in over 90% of patients after 6 months, with consistent results up to 12 months, mirroring prior global data. A long-term study of the 3-month depot in girls showed sustained inhibition of sex steroids, slowed skeletal maturation (bone age advance reduced to 0.4 years per chronological year), and height gains aligning with target heights after 2–5 years of treatment. Comparative analyses indicate no significant efficacy differences versus leuprolide, another GnRH agonist, in suppressing pubertal progression or advancing final height. Standard dosing involves a single 22.5 mg intramuscular injection every 6 months for children weighing at least 22 kg, with monitoring of LH, FSH, estradiol (in girls), testosterone (in boys), and bone age to assess response and guide discontinuation upon pubertal age attainment. Long-term outcomes from retrospective and follow-up studies demonstrate improved final adult heights (e.g., gains of 5–7 cm over pretreatment predictions in treated cohorts) without adverse effects on fertility or reproductive function in adulthood. Safety profiles align with GnRH agonist class effects, including injection-site reactions and transient initial hormone flares, but trials report no serious treatment-related adverse events beyond these, with effective suppression maintained over years. Discontinuation typically restores normal pubertal progression without rebound acceleration.

Gynecological conditions

Triptorelin, a gonadotropin-releasing hormone (GnRH) agonist, is utilized in gynecological practice primarily for conditions driven by estrogen-dependent tissue proliferation, such as endometriosis, uterine fibroids (leiomyomas), and adenomyosis. By inducing a hypoestrogenic state through pituitary desensitization, it reduces lesion size, alleviates symptoms like dysmenorrhea, dyspareunia, chronic pelvic pain, and heavy menstrual bleeding, and may facilitate subsequent surgical or conservative management. Treatment durations typically range from 3 to 6 months, often with add-back hormone therapy to mitigate menopausal-like side effects, though long-term use is limited by bone density concerns. In endometriosis, particularly deep infiltrating forms, triptorelin monotherapy or adjunctive therapy post-conservative surgery yields sustained symptom relief. A multicenter prospective study of up to 24 weeks of triptorelin following surgery for deep infiltrating endometriosis reported significant improvements in pain scores and low recurrence rates over 24 months of follow-up, with over 90% of patients experiencing reduced dysmenorrhea and dyspareunia. A randomized placebo-controlled trial confirmed triptorelin's superiority in reducing endometriosis-associated pain, with treated patients showing lower revised American Fertility Society scores for adhesions and implants compared to placebo. Comparative assessments of formulations, such as 3-month pamoate versus 1-month acetate, demonstrated noninferior estradiol suppression and symptom control in over 98% of cases. For uterine fibroids, triptorelin serves as preoperative therapy to shrink tumors and decrease bleeding risk, enabling less invasive procedures. In a clinical trial involving monthly 3.75 mg injections for 3 months before hysterectomy, women achieved significant fibroid volume reduction (up to 40-50% in some cohorts) and uterine size decrease, correlating with improved surgical outcomes. Randomized comparisons with aromatase inhibitors like showed triptorelin's comparable efficacy in myoma volume reduction over 12 weeks, though with greater hypoestrogenic effects. Guidelines recommend its use for symptom control prior to myomectomy or hysterectomy, particularly in cases of heavy bleeding or anemia. Adenomyosis responds favorably to triptorelin, with multicenter observational data indicating rapid symptom amelioration. A study of 3.75 mg monthly injections for 3-6 months in 120 patients reported marked reductions in heavy menstrual bleeding (from baseline scores >7 to <3 on visual analog scales) and , alongside improved uterine morphology on imaging and enhanced outcomes in reproductive-age subsets, with 70% achieving post-treatment. Adverse events were primarily and manageable, supporting its role in both symptomatic relief and fertility preservation strategies. No serious treatment-related complications were noted across cohorts.

Other indications

Triptorelin is approved in the for adjuvant treatment of hormone receptor-positive early-stage in premenopausal women, typically in combination with or an to suppress ovarian function and reduce levels. In the United States, while not explicitly FDA-approved for this indication, it is used off-label for similar purposes in premenopausal patients with advanced or hormone-sensitive , often alongside endocrine therapies like and . Clinical trials have demonstrated that GnRH agonists like triptorelin improve disease-free survival in this population by inducing chemical ovarian , with data from randomized studies showing hazard ratios for recurrence of approximately 0.72 when added to . In assisted reproductive technologies, triptorelin serves as an adjunct for pituitary downregulation during controlled ovarian stimulation in IVF cycles, particularly in long protocols to prevent premature surges. Reduced doses, such as 0.1 mg, have been evaluated for flare-up protocols or support, with studies indicating comparable implantation rates to higher doses or alternative GnRH agonists like leuprolide, though without significant improvements in overall outcomes. It is also employed as a trigger for final maturation in GnRH cycles, leveraging the initial flare effect, with meta-analyses reporting live birth rates of 25-30% in such regimens. Off-label use of triptorelin as a suppressant in adolescents with has increased, particularly in protocols aiming to delay secondary sex characteristics, but this application lacks specific regulatory approval and relies on extrapolation from data. Systematic reviews highlight limited long-term evidence for safety and efficacy in this context, with concerns over loss, potential impacts on , and unresolved questions about persistence of , as fewer than 20% of treated youth in some cohorts desist post-suppression. Peer-reviewed analyses emphasize that such use is experimental, with calls for randomized controlled trials amid reports of adverse events like mood alterations and sterile abscesses.

Safety profile

Common adverse effects

The most common adverse effects of triptorelin arise from its action as a (GnRH) agonist, which initially stimulates followed by sustained suppression of gonadal production, resulting in hypoestrogenic or hypogonadal states. These effects vary by indication and but frequently include symptoms such as hot flushes, reported in 58% to 73% of adult males receiving intramuscular depot formulations for across clinical trials involving 3.75 mg, 11.25 mg, or 22.5 mg doses. Skeletal pain occurs in 12% to 13% of such patients, often linked to underlying disease progression or testosterone fluctuations. In adult males, additional frequent effects encompass (7% to 10%), (5% to 7%), decreased , and lower extremity or (5% to 6%), with incidences derived from controlled studies where events ≥5% were tabulated. Local injection site reactions, including , are reported across formulations due to intramuscular or . For central in pediatric patients, injection site reactions predominate, with pain in 45%, redness in 14%, and swelling or pruritus in 2% to 3%; affects 14%, while hot flushes occur in about 5%. is noted in 8% of females in this group. In gynecological applications such as , menopausal-like symptoms including hot flushes and are commonly observed, aligning with hypoestrogenic effects seen in trials where such vasomotor disturbances affected a majority of treated women. Overall, these effects are generally reversible upon discontinuation, though monitoring is advised due to potential of underlying conditions during initial testosterone or surges.

Serious risks and long-term effects

Triptorelin administration can precipitate a transient surge in gonadotropins and sex hormones due to its agonistic action on GnRH receptors, potentially exacerbating symptoms in hormone-sensitive conditions such as advanced through tumor flare syndrome, which manifests as intensified , , or ureteral obstruction in approximately 5-10% of cases during initial treatment. This risk necessitates concurrent anti-androgen therapy or careful monitoring in high-risk patients. Cardiovascular events represent a significant serious , with GnRH agonists like triptorelin linked to elevated incidences of , , and sudden cardiac death, particularly in men undergoing for ; observational data indicate a 20% higher of incident coronary heart disease compared to non-users, attributed to hypogonadism-induced metabolic shifts including and . This association persists across multiple cohort studies, though causality remains debated due to factors like underlying comorbidities. Prolonged triptorelin-induced substantially impairs density, elevating fracture risk by up to 20-30% in long-term users, as and testosterone suppression disrupts activity and calcium ; this effect is dose- and duration-dependent, with annual bone loss rates of 2-5% observed in adults on . In pediatric patients treated for central , accrual diminishes during therapy (Z-scores dropping by 0.5-1.0 SD), but typically normalizes within 1-2 years post-discontinuation, though peak bone mass attainment may be subtly affected if treatment extends beyond 3-4 years. Long-term fertility outcomes following triptorelin use in children with show puberty resumption in over 95% of cases after cessation, with preserved ovarian function and successful pregnancies reported in cohort studies tracking patients into adulthood; however, subtle delays in or reduced cannot be ruled out without larger prospective data. Metabolic derangements, including and , may persist post-treatment in some adolescents, potentially compounding cardiovascular vulnerability into adulthood. Rare but serious hypersensitivity reactions, including , have been documented via databases, underscoring the need for immediate intervention.

Administration and dosing

Standard regimens

Triptorelin is administered exclusively via into the buttock, using depot formulations that provide sustained release over weeks to months. The lyophilized powder must be reconstituted with sterile immediately prior to administration, and the suspension injected promptly to avoid settling. Dosage strengths are not interchangeable or additive; the chosen determines the interval between doses. duration varies by indication, typically continuing until disease progression, symptom resolution, or as limited by safety concerns like loss. For advanced , standard initial therapy often begins with the 3.75 mg dose every 4 weeks to assess tolerance and monitor for tumor , though longer-acting formulations may be used from the outset based on physician judgment. Recommended regimens include 3.75 mg every 4 weeks, 11.25 mg every 12 weeks, or 22.5 mg every 24 weeks, with serum testosterone and levels monitored to confirm castrate levels (typically achieved by day 29) and therapeutic efficacy. In central for children aged 2 years and older, the approved regimen is 22.5 mg every 24 weeks, with efficacy assessed via suppression, sex steroid levels, height velocity, and progression 1-2 months post-initiation and periodically thereafter. Treatment is discontinued at the age of anticipated natural onset. For gynecological conditions like or uterine fibroids—primarily approved outside the —a typical regimen involves 3.75 mg every 4 weeks for 3-6 months to achieve hypoestrogenic suppression, often combined with progestin add-back therapy to reduce adverse effects such as symptoms and bone loss.
IndicationFormulation DoseFrequencyKey Monitoring
Advanced prostate cancer3.75 mgEvery 4 weeksTestosterone, PSA levels
Advanced prostate cancer11.25 mgEvery 12 weeksTestosterone, PSA levels
Advanced prostate cancer22.5 mgEvery 24 weeksTestosterone, PSA levels
Central precocious puberty22.5 mgEvery 24 weeksLH, sex steroids, growth
Endometriosis/fibroids*3.75 mgEvery 4 weeksSymptom relief,
*Regimen per international guidelines; limited U.S. approval for these uses.

Formulation-specific considerations

Triptorelin is formulated primarily as pamoate (embonate) salt for sustained-release depot injections, with salt used in some immediate-release contexts, though depots predominate clinically to achieve prolonged suppression. Depot formulations incorporate triptorelin pamoate into biodegradable microspheres, enabling intramuscular release over 1, 3, or 6 months via doses of 3.75 mg, 11.25 mg, or 22.5 mg, respectively, which reduces injection frequency and improves adherence compared to daily subcutaneous regimens. Pharmacokinetics vary by duration: all depots exhibit an initial burst release peaking within hours post-injection, potentially inducing a transient testosterone surge (flare) before sustained suppression, but longer-acting versions maintain castrate levels (<50 ng/dL) for the full interval with minimal fluctuations, as evidenced by plasma profiles showing rapid C_max followed by pseudo-steady state decline. Shorter 1-month formulations may require more frequent dosing, increasing procedural burden and site reaction risk, while 6-month options demand precise timing to avoid gaps in suppression, particularly in where consistent gonadal inhibition is critical. Administration requires reconstitution with provided diluent, into gluteal or using specific needles to avoid clogging from microspheres, with recent data supporting subcutaneous feasibility for 3-month pamoate without efficacy loss, potentially easing delivery in pediatric or outpatient settings. Formulation choice should account for patient factors like body mass (higher BMI may alter absorption in subcutaneous routes) and indication duration, with confirmed across brands for hormonal endpoints but monitoring recommended for inter-patient variability in release.

History and development

Discovery and early research

Triptorelin, a synthetic decapeptide analog of (GnRH) featuring a D-tryptophan substitution at the sixth position in place of , was first synthesized in the mid-1970s. This structural modification enhanced its potency, duration of action, and resistance to enzymatic degradation compared to native GnRH, which consists of 10 and was structurally elucidated by Andrew V. Schally and colleagues in 1971. The synthesis was conducted in Schally's laboratory at , where Schally, a pioneer in hypothalamic hormone research, co-invented the compound as part of efforts to develop superagonists for therapeutic applications. Initial evaluations, detailed in a 1977 U.S. patent, demonstrated triptorelin's superior (LH)- and (FSH)-releasing activity in animal models at dosages as low as 0.1-1 μg/kg, outperforming native GnRH by factors of 10-50 in stimulating pituitary secretion. These preclinical studies, primarily in , confirmed its rapid onset of action following subcutaneous or intravenous administration, with peak LH release occurring within 15-30 minutes. Schally's team highlighted its potential for treating and through short-term stimulation, while noting the risk of —receptor desensitization—with repeated dosing. Further early research in the late explored triptorelin's inhibitory effects upon chronic administration, revealing downregulation of GnRH receptors in the pituitary, which suppressed endogenous and gonadal steroid production. In ovariectomized models, it restored LH levels to precastration baselines without affecting basal secretion in intact animals, underscoring its specificity. These findings, building on Schally's foundational work recognized by the 1977 in or , established triptorelin's dual-phase mechanism: initial hyperstimulation followed by sustained suppression, paving the way for applications in endocrine disorders and hormone-dependent cancers.

Regulatory approvals and milestones

Triptorelin was first approved for medical use in in 1986 under the brand name Decapeptyl for indications including and gynecological disorders. By the early , it had received marketing authorizations in multiple European countries, with national approvals expanding to over 60 nations by 2006. In the , triptorelin has primarily been authorized through national procedures rather than centralized EMA approval for initial indications, reflecting its early development and decentralized regulatory pathway. In the United States, the (FDA) granted initial approval to triptorelin pamoate (Trelstar) 3.75 mg on June 15, 2000, for the palliative treatment of advanced . This was followed by approval of the 11.25 mg three-month (Trelstar LA) in 2001. The six-month 22.5 mg for received FDA approval on March 15, 2010, providing a longer-duration option supported by phase III efficacy and safety data. Key pediatric milestones include European approval of the six-month 22.5 mg formulation (Decapeptyl and Pamorelin) for central on January 9, 2017, in 22 countries via decentralized procedure. The FDA approved Triptodur (triptorelin) 22.5 mg for the same indication on June 29, 2017, based on a pivotal phase III trial demonstrating suppression of levels. Earlier, the six-month formulation for completed Europe's decentralized procedure in October 2009, enabling broader commercialization.

Society, regulation, and market

Brand names and

Triptorelin is marketed under multiple brand names worldwide, with formulations varying by and indication. In the United States, it is available as Trelstar (triptorelin pamoate) for palliative treatment of advanced , approved by the FDA on June 15, 2000, and manufactured by Verity Pharmaceuticals. Another U.S. brand, Triptodur, is indicated for central in pediatric patients. Internationally, Decapeptyl (triptorelin pamoate or acetate) is a primary brand produced by , used for , , uterine fibroids, and . Other notable brands include Pamorelin by Debiopharm, with Swissmedic approval for of 3.75 mg and 11.25 mg formulations for as of May 16, 2025. Diphereline and Gonapeptyl are additional brands available in select markets for similar indications.
Brand NameManufacturerKey Indications and Notes
TrelstarVerity PharmaceuticalsAdvanced (U.S.)
TriptodurVariousCentral (U.S.)
Decapeptyl, endometriosis, (global, excluding U.S.)
PamorelinDebiopharm, including subcutaneous option (Europe/)
Triptorelin is approved and available in over 100 countries, including the , members, (with 1-month and 3-month prolonged-release formulations), , and others, though specific indications and formulations may differ by jurisdiction. In some regions, it is restricted to certain uses or available only for veterinary applications. Generic versions of triptorelin pamoate exist in limited markets, but branded products predominate due to protections. Triptorelin is approved by the (FDA) for the palliative treatment of advanced , with Trelstar receiving initial approval on June 15, 2000. The FDA also approved Triptodur, a formulation for central in children aged 2 years and older, on June 29, 2017. In the , triptorelin holds national authorizations across member states for indications including , , and , as listed in procedures updated through 2022. It is classified as a but not a under U.S. or EU drug scheduling systems. Regulatory restrictions have emerged concerning of triptorelin and similar GnRH agonists as puberty suppressants for adolescents experiencing . In the , regulations effective May 29, 2024, prohibit prescribing such hormones to individuals under 18 outside approved clinical trials, following reviews questioning and in this context. In the , as of 2024, at least 24 states have enacted laws restricting or banning puberty blockers for minors in treatment, often requiring exceptions only under stringent medical criteria. These measures reflect concerns over insufficient long-term data, with approvals limited to conditions like where puberty onset is pathologically early rather than socially influenced. Ethically, off-label administration of triptorelin to minors for has sparked debate over consent validity and risk-benefit assessment, as adolescents may lack full capacity to weigh irreversible effects like impairment or loss. Italy's National Committee for conditionally endorsed this use in 2018, permitting it under multidisciplinary oversight, yet later analyses emphasize gaps in for psychological benefits and potential overmedicalization of identity issues. In , long-term off-label prescribing in gender clinics persists despite label restrictions to short-term use, raising questions about deviation from manufacturer guidelines and prioritization of demand over causal of harm prevention. Proponents cite temporary suppression to alleviate distress, but detractors, drawing from data showing off-label signals for adverse events in younger cohorts, argue it constitutes experimental intervention without robust randomized trials establishing net benefits.

Research and controversies

Ongoing clinical investigations

As of October 2025, several phase III clinical trials are actively investigating triptorelin's role in fertility preservation among adolescents and young adults (AYAs) undergoing chemotherapy for cancer. One multicenter randomized trial (NCT06513962) is recruiting participants to compare triptorelin administration versus observation alone in preventing ovarian damage, with primary endpoints focusing on post-treatment ovarian reserve markers such as anti-Müllerian hormone levels; the study targets females up to age 39 with newly diagnosed hematopoietic or solid tumors requiring gonadotoxic therapy. This builds on prior evidence of GnRH agonists' potential chemoprotective effects, though long-term fertility outcomes remain under evaluation. In pediatric , ongoing studies assess extended-release formulations for (CPP). A phase III (NCT05029622) evaluates the 6-month triptorelin pamoate depot's efficacy in suppressing and pubertal progression in children aged 2-9, with monitoring for growth and ; recruitment status indicates active enrollment as of early 2025. Similarly, long-term observational investigations, such as those tracking final and post-triptorelin in CPP girls, continue to refine dosing regimens and predictors of response, prioritizing 3-month versus 6-month intervals to minimize injection frequency while maintaining suppression. For hormone receptor-positive early , a prospective study (NCT05377684) is examining triptorelin combined with endocrine in premenopausal women, with endpoints including quality-of-life metrics via validated scales and serial profiling to assess menopausal symptom burden and adherence. In advanced , population-specific trials like NCT05590793 test the 6-month formulation's testosterone suppression and tolerability in Chinese adults, addressing potential ethnic variations in . These efforts emphasize real-world safety, including injection-site reactions and cardiovascular risks, amid calls for larger datasets on rare adverse events reported in analyses. Overall, investigations prioritize optimized delivery systems and expanded indications, with interim data supporting triptorelin's established mechanism but highlighting needs for randomized controls in off-label contexts.

Debates on off-label applications

Triptorelin, a (GnRH) analogue, has been employed off-label to suppress in adolescents with , despite lacking specific regulatory approval for this indication in most jurisdictions. This application aims to alleviate psychological distress by halting endogenous pubertal changes, providing time for exploration before potential transition steps. Proponents argue it offers reversible intervention with benefits, citing observational data from clinics like the UK's , where triptorelin use correlated with reduced ideation in select cohorts.30099-2/fulltext) However, such evidence is predominantly low-quality, relying on non-randomized, short-term studies prone to and lacking long-term controls. Critics highlight insufficient demonstration of net benefits, with systematic reviews, including the UK's Cass Review (2024), concluding that evidence for improved outcomes or is weak and inconclusive. Risks include decreased density, potential fertility impairment, and impacts on cognitive and development, as GnRH agonists disrupt normal pubertal processes essential for brain maturation. Adverse event databases like FAERS report disproportionate signals for off-label pediatric use, including serious events like death in older groups, though causality remains unestablished. Italian bioethics discussions, via the National Committee for Bioethics (2018 endorsement, revisited 2024), underscore consent challenges, noting adolescents' limited capacity to weigh irreversible effects against uncertain gains. Regulatory responses reflect caution: England's NHS restricted blockers to research settings post-Cass (2024), citing experimental status; similar scrutiny in and prioritizes over pharmacological suppression due to evidentiary gaps. Ethical debates invoke the "child's right to an open future," arguing forecloses natural development paths without robust proof of necessity, potentially medicalizing distress better addressed through exploratory therapy. Peer-reviewed analyses emphasize that while safe for approved treatment, extrapolation to ignores condition-specific differences in and response. Other off-label debates, such as adjunctive use in assisted reproduction for support, center on protocol variability rather than safety, with trials showing mixed efficacy in sustaining implantation rates without consensus on dosing. These remain niche compared to controversies, where institutional biases in gender clinics—often favoring affirmative models—have amplified uncritical adoption, as critiqued in independent reviews.

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