Triptorelin

Origin and structure

Triptorelin is a modified form of gonadotrophin-releasing hormone (GnRH, also called LHRH or gonadorelin), the ten-amino-acid hormone that the hypothalamus releases in pulses to make the pituitary produce LH and FSH. In 1976 a team that included Andrew Schally reported that replacing the glycine at position 6 with a D-amino acid gave much stronger analogues; the version with D-tryptophan, [D-Trp6]-LHRH, was 13 times as active as the natural hormone at releasing LH in immature male rats. That peptide is triptorelin: pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2, formula C64H82N18O13, molar mass about 1311 g/mol.

On its own the peptide is cleared within hours: after an injection under the skin its half-life is about 3 to 5 hours. The medicines therefore come in two kinds. Daily injections of triptorelin acetate are used in IVF. Depots, made with the acetate or with the pamoate salt (also called embonate), are polymer microgranules that release the peptide over one, three or six months.

Brand names differ by country. In Europe it is sold as Decapeptyl (Ferring in the Netherlands, Ipsen in France), Gonapeptyl (Ferring, in several other EU countries), Pamorelin, Diphereline and Salvacyl (Ipsen) and Triptofem (Goodlife Pharma); in the US as Trelstar (Verity) and Triptodur (Azurity, a Debiopharm trademark).

How it works

Natural GnRH works because it arrives in pulses. Triptorelin binds the same receptor on the pituitary more strongly and keeps it occupied; in the laboratory studies cited on the US label it was 100 times more active than GnRH at releasing LH from rat pituitary cells and 20 times better at displacing it from the receptor. The effect therefore comes in two phases. First there is a surge: LH, FSH and testosterone or oestradiol rise, and testosterone peaks two to four days after a depot injection. With continued exposure the pituitary cells become desensitised and LH and FSH output falls; after two to four weeks testosterone in men drops to the level seen after surgical castration, and oestrogen in women to postmenopausal values. The effect is usually reversible once treatment stops.

Each use builds on one of these phases. In prostate cancer, breast cancer, endometriosis, fibroids and early puberty the aim is the shutdown, and the initial surge is a drawback: it can briefly worsen prostate-cancer symptoms, which is why the EU product information advises considering an anti-androgen at the start. In IVF, daily injections keep the pituitary quiet so that the ovaries can be stimulated without a premature LH surge. A single injection in a cycle controlled with a GnRH antagonist is used for the opposite effect: a short LH surge that triggers the final maturation of the eggs.

Is triptorelin approved?

Yes. Triptorelin is a prescription medicine in the EU and the US, with indications that differ by product and country.

In the EU there is no central licence from the EMA: each product is authorised by national regulators, often through procedures shared by several countries. In 2022 the EMA's safety committee (PRAC) assessed the periodic safety reports for all of them together. Following that review, the national product information was updated in 2023 with a warning about idiopathic intracranial hypertension (raised pressure in the skull) in children and with fatty liver among the metabolic changes in men.

In the Netherlands triptorelin is prescription-only. The Farmacotherapeutisch Kompas lists Decapeptyl (a daily IVF injection and the CR depot, Ferring), Pamorelin (one-, three- and six-month depots, Ipsen), Salvacyl (a three-month depot, Ipsen) and Triptofem (a daily IVF injection, Goodlife Pharma).

Research-grade triptorelin, the freeze-dried peptide sold for laboratory use, is none of these. It has no marketing authorisation, is not made under a medicines licence, and may not be used in people. The approvals below describe the licensed products only.

• Netherlands: registered for locally advanced or metastatic hormone-dependent prostate cancer, and high-risk localised or locally advanced prostate cancer together with radiotherapy; hormone-receptor-positive early breast cancer in women at high risk of recurrence who are still premenopausal after chemotherapy, with tamoxifen or an aromatase inhibitor; symptomatic endometriosis confirmed by laparoscopy; shrinking fibroids before surgery; central precocious puberty; suppressing the pituitary before and during ovarian stimulation for IVF; and, with psychotherapy, reducing sexual drive in adult men with severe paraphilias (Salvacyl).
• US: Trelstar was approved on 15 June 2000 as a monthly depot for advanced prostate cancer, followed by a three-month depot on 29 June 2001 and a six-month depot on 10 March 2010. Triptodur, a six-month depot, was approved on 29 June 2017 for central precocious puberty in children aged 2 and over. No US product is approved for IVF, endometriosis or breast cancer. In 2025 both US labels added a warning for severe skin reactions such as Stevens-Johnson syndrome, DRESS and AGEP.

What the research shows

The evidence comes from the registration trials of the depots, large cancer trials in which triptorelin was the main way to suppress hormones, and fertility trials of GnRH agonists. The main results:

• Prostate cancer, head to head (BJU Int 2003): 284 men with advanced prostate cancer were randomised to monthly triptorelin or leuprorelin for nine months. Testosterone reached castrate levels more slowly with triptorelin (91.2% against 99.3% at day 29) but equally often by day 57 (97.7% against 97.1%), and castration was maintained as well. Survival at nine months was higher with triptorelin (97.0% against 90.5%), but that was a secondary endpoint the trial was not designed to test.
• Longer depots (US registration trials): the three-month depot, randomised against the monthly one in 346 men, brought 97.7% of 171 evaluable men to castrate levels by day 29, and 94.4% stayed there to day 253. The six-month depot was tested without a comparison group in 120 men: 97.5% by day 29 and 93.3% maintained to day 337.
• With radiotherapy, EORTC 22961: 970 men with locally advanced prostate cancer received radiotherapy plus androgen suppression with a GnRH agonist, triptorelin in 62.2%. Stopping after six months instead of three years raised five-year mortality from 15.2% to 19.0%.
• Breast cancer, SOFT and TEXT: premenopausal women with hormone-receptor-positive early breast cancer; triptorelin was the means of ovarian suppression for 91% of the SOFT participants who had it and for all women in TEXT; the others in SOFT had surgery or radiotherapy of the ovaries. After eight years in SOFT (NEJM 2018), 78.9% were free of disease on tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression and 85.9% with exemestane plus ovarian suppression.
• Central precocious puberty: in a trial of the six-month depot without a control group, LH stayed at prepubertal levels in 93 to 98% of 44 children aged 2 to 9 at each visit over a year; at 12 months sexual development had stabilised in 89%, and in 95% bone age had not advanced faster than age.
• IVF trigger (not a licensed indication in the Netherlands): a 2014 Cochrane review of 17 randomised trials (1,847 women) compared a GnRH-agonist trigger, such as triptorelin, with hCG in cycles controlled with a GnRH antagonist. With a fresh embryo transfer the agonist sharply reduced ovarian hyperstimulation syndrome (odds ratio 0.15) but also lowered the live-birth rate (odds ratio 0.47); the authors see a place for it when no fresh transfer is planned, in egg donors and when eggs are frozen.
• Puberty suppression in transgender adolescents (off-label): the gender clinic of Amsterdam UMC has used triptorelin to pause puberty, and a 2024 study from that clinic followed body-composition changes in 548 adolescents treated this way. A 2024 systematic review of 50 studies on puberty suppression for gender dysphoria rated only one as high quality: puberty was reliably suppressed and bone density fell during treatment, but no conclusions could be drawn about effects on gender dysphoria, mental health or cognitive development.

Side effects and warnings

Most side effects follow from the lowered sex hormones. In the US prostate-cancer trials, hot flushes were judged treatment-related in 59 to 73% of men, depending on the depot, and skeletal pain in 12 to 13% on the one- and three-month depots; on the six-month depot, 10% reported erectile dysfunction and 7.5% testicular shrinkage. The Dutch product information lists loss of libido, erectile dysfunction, sweating, weakness and tingling in the legs as very common in men, and in women hot flushes, sleep and mood problems, headache, vaginal dryness, pain during sex and bleeding in the first month. In the US trial in children with early puberty, pain at the injection site was reported in 45% and headache in 13.6%.

In the first weeks, the testosterone surge can worsen prostate cancer, with bone pain, urinary blockage and, in men with spinal metastases, spinal cord compression. Long-term suppression thins the bones: the Farmacotherapeutisch Kompas puts the loss at about 1% a month during a six-month course, largely recovered within six to nine months after stopping. The labels also warn of depression, which can be severe (in SOFT and TEXT about half of the women reported depression, and fewer than 5% had severe depression), convulsions, bleeding into an undiagnosed pituitary adenoma, and, during androgen deprivation, raised blood sugar and diabetes, fatty liver, cardiovascular disease and a longer QT interval on the ECG.

In children the labels warn of idiopathic intracranial hypertension (raised pressure in the skull, with headache and visual problems) and mood changes, and the Dutch information mentions a slipped growth plate at the top of the thigh bone after treatment has stopped. Triptorelin is not for use in pregnancy.

Frequently asked questions

Is triptorelin legal in the Netherlands?

As a medicine, yes, but only on prescription. Decapeptyl, Pamorelin, Salvacyl and Triptofem are registered in the Netherlands, for uses from prostate cancer to IVF. Research-grade triptorelin is not a registered medicine: it is not made or checked as one, and it may not be used in people.

Is triptorelin banned in sport?

For men, yes, at all times, in and out of competition. The WADA Prohibited List 2026 names GnRH and its agonist analogues, with triptorelin by name, in class S2.2.1, testosterone-stimulating peptides in males. It is not prohibited for women. The Dutch translation of the list by the Dopingautoriteit carries the same text.

What is the difference between Decapeptyl, Pamorelin, Gonapeptyl and Trelstar?

All contain triptorelin; they differ in salt, release time and licensed use. The daily injections (Decapeptyl 0.1 mg, Gonapeptyl Daily, Triptofem) are for IVF. The one-, three- and six-month depots (Decapeptyl CR, Pamorelin, Gonapeptyl Depot, Trelstar, Triptodur) are for prostate and breast cancer, endometriosis, fibroids or early puberty, depending on the product and the country. The depot strengths are separate formulations, not multiples of one another.

Why does triptorelin first raise testosterone?

Because it is an agonist: it first stimulates the GnRH receptor, so LH and testosterone rise, with testosterone peaking two to four days after a depot injection. Only after the pituitary has become desensitised does testosterone fall, reaching castrate levels after about three to four weeks. In prostate cancer this flare can briefly worsen symptoms, which is why the EU product information advises considering an anti-androgen at the start.

Is triptorelin a puberty blocker?

Yes, it is one of the GnRH analogues used as puberty blockers. Its licensed use is central precocious puberty, puberty that the brain starts too early: in the Dutch information for Pamorelin, first signs before age 8 in girls or 10 in boys, in children aged 2 and over. Off-label, the Amsterdam UMC gender clinic has used it to pause puberty in transgender adolescents; a 2024 systematic review found the evidence for that use too weak to draw conclusions about gender dysphoria or mental health, and found that bone density fell during treatment.

Is research-grade triptorelin the same as Decapeptyl?

No. Decapeptyl and the other brands are licensed medicines with a known dose, made sterile under pharmaceutical rules, and most are slow-release depots built from polymer microgranules. A freeze-dried peptide sold for laboratory use is neither: its identity and purity are what its certificate of analysis says, nothing more, it releases nothing slowly, and it may not be used in people.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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