Is histrelin FDA-approved, and what does the research show?

What is histrelin?

Histrelin is a man-made peptide, a short chain of amino acids, the building blocks of proteins ¹. The Supprelin LA label calls it "a synthetic nonapeptide analog of the naturally occurring gonadotropin releasing hormone (GnRH)," a nonapeptide being a chain of nine ¹. An analog is a modified copy, and the label says this one has "a greater potency than the natural sequence hormone" ¹. Natural GnRH acts on the pituitary gland, a hormone gland at the base of the brain, which in turn switches on the ovaries and testes ¹.

Histrelin is not a wellness, weight-loss or performance peptide. It is a specialist drug that turns sex-hormone production down ¹. Supprelin LA, an implant, is for children whose puberty has started too early ¹. Vantas, a second implant, was approved for men with advanced prostate cancer ³. The first histrelin product, Supprelin, was an injection approved in 1991 ⁵.

Drugs@FDA lists Vantas and the Supprelin injection as "Discontinued" ⁴, ⁵. FDA withdrew the injection's approval effective September 17, 2003 ⁶. The label of each implant describes "a small thin flexible tube" placed under the skin ¹, ³. The Vantas label adds that histrelin "is not active when given orally" ³.

Is histrelin FDA-approved?

Yes, as a prescription drug. Drugs@FDA lists histrelin under three brand names, and Supprelin LA, approved for one use in children, is the only one not listed as "Discontinued" ², ⁴, ⁵. FDA approved Supprelin LA (histrelin acetate) subcutaneous implant on May 3, 2007, under new drug application (NDA) 022058 ². Subcutaneous means under the skin. Drugs@FDA lists it with marketing status "Prescription" as of November 9, 2026, the date of the record's data ².

The label says Supprelin LA "is indicated for the treatment of children with central precocious puberty (CPP)" ¹. Children with CPP, it explains, "have an early onset of secondary sexual characteristics (earlier than 8 years of age in females and 9 years of age in males)" ¹. Secondary sexual characteristics are the body changes of puberty, such as breast development ¹. These children also show "a significantly advanced bone age that can result in diminished adult height attainment" ¹. In plain words, their bones mature ahead of schedule, which can leave them shorter as adults ¹.

The word "central" means that the early puberty starts with signals from the brain and the pituitary gland. Use in children under 2 years "is not recommended" ¹.

A second histrelin implant, Vantas, was approved on October 12, 2004, under NDA 021732 ⁴. Its label says Vantas "is indicated for the palliative treatment of advanced prostate cancer" ³. Palliative treatment eases a disease and its symptoms without curing it. The label adds that Vantas "is not indicated for use in pediatric patients" ³. Drugs@FDA lists Vantas with marketing status "Discontinued" as of November 9, 2026, the date of the record's data ⁴.

Drugs@FDA names Endo Operations as the sponsor of both implants ², ⁴. A KHN and NPR story by Sydney Lupkin, published by MDedge on November 10, 2021, said Endo had told FDA that September that it had stopped making Vantas ⁷. The story quoted the company's explanation: a manufacturing problem for which it could not find "a suitable corrective action that resolves the issue" ⁷. The company also told the reporters that Supprelin LA and Vantas are "not identical products" ⁷.

The first histrelin product was an injection. Drugs@FDA holds Supprelin, a histrelin acetate injection, under NDA 019836, approved December 24, 1991, and lists it as "Discontinued" ⁵. The Supprelin LA label gives histrelin's "Initial U.S. Approval" as 1991 ¹.

FDA's 2007 review of Supprelin LA says histrelin acetate "was approved in 1991 for CPP as a daily subcutaneous injection" ⁸. FDA withdrew the injection's approval "effective September 17, 2003" ⁶. The notice says the holders of the applications it lists had told FDA "that the drug products were no longer marketed and requested that the approval of the applications be withdrawn" ⁶.

See the FDA status of every peptide, updated weekly.

How does histrelin work?

Histrelin switches on the pituitary's GnRH receptors and, by never letting up, makes the gland stop responding ¹. The Supprelin LA label's term for it is "a GnRH agonist and an inhibitor of gonadotropin secretion when given continuously" ¹. An agonist is a drug that activates a receptor. The gonadotropins are luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the two pituitary hormones that prompt the ovaries and testes to make sex hormones ¹.

The first effect is a rise, not a fall ¹. In the first week, the label says, histrelin "causes a transient increase in serum concentrations of estradiol in females and testosterone in both sexes" ¹. Estradiol is an estrogen ¹. A child may briefly show more signs of puberty, and the patient guide names "light vaginal bleeding and breast enlargement in girls" ¹. In 17 men with prostate cancer, mean testosterone rose from 376.4 to 530.5 nanograms per deciliter of blood on day 2 after a Vantas implant ³.

Then the pituitary adapts. Continuous exposure "causes a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes," the cells that make LH and FSH ¹. With fewer working receptors the gland releases less LH and FSH, and the ovaries and testes make less hormone ¹. The implant is what keeps the exposure continuous: both labels describe a reservoir that releases the drug steadily over 12 months ¹, ³.

In children with CPP, the Supprelin LA label says LH falls "to prepubertal levels within 1 month of treatment," and sex-hormone levels follow ¹. Within 4 weeks, it says, "suppression of gonadal steroids occurs and manifestations of puberty decrease" ¹. Gonadal steroids are the sex hormones that the ovaries and testes make. After that, "secondary sexual development ceases to progress in most patients" ¹. Growth in height also slows, "which improves the chance of attaining predicted adult height" ¹.

In men, the Vantas label says, "testosterone is reduced to castration levels" within 2 to 4 weeks of the start of treatment ³. Castration levels are the low testosterone levels of a man whose testes have been removed. Both labels cite "animal and human studies" for this mechanism ¹, ³.

What does the research show?

The Supprelin LA label reports two small studies in children with central precocious puberty, and neither had a comparison group ¹. Both were single-arm and open-label: every child received the implant, and everyone knew it ¹. Study 1 enrolled 11 girls aged 3.7 to 11.0 years, all of them treated before ¹. Study 2 enrolled 36 children, 33 girls and 3 boys, aged 4.5 to 11.6 years ¹. Sixteen of the 36 had been treated before and 20 were new to treatment ¹.

Study 2's main measure was LH suppression ¹. The label defines it as a peak LH below 4 milli-international units per milliliter (mIU/mL) after a stimulation test with a GnRH analog ¹. In a stimulation test, a dose of the analog is given and the rise in LH is measured afterward. One month after implantation, LH was suppressed in all 20 children new to treatment and remained suppressed in all 16 treated before ¹. That held through month 12 ¹.

Estradiol was suppressed in all 33 girls through month 9 and in 97 percent at month 12 ¹. Testosterone stayed suppressed in the 3 boys, all of whom had been treated before ¹. Other measures, among them bone age, growth in height and the clinical signs of puberty, "indicated stabilization of disease" ¹. The label describes Study 1's results as "consistent with that observed in Study 2" ¹.

Studied in people: a phase 3, open-label trial of a histrelin implant at nine U.S. medical centers followed 36 children with CPP for one year ⁹. Phase 3 is the last stage of testing before a drug is submitted for approval. The trial was published online on February 27, 2007 ⁹. In the 20 children new to treatment, mean peak LH fell from 28.2 to 0.8 mIU/mL by one month (P < 0.0001, a change very unlikely to be chance) ⁹. In the children treated before, it went from 2.1 to 0.5 mIU/mL ⁹.

Estradiol, measured in girls, fell from 24.5 to 5.9 picograms per milliliter in the group new to treatment (P = 0.0016) ⁹. The authors reported no significant adverse events and said suppression was maintained throughout the study ⁹. The Supprelin LA label, for its part, reports two serious adverse reactions among the 47 children in its two studies ¹. The trial's 2015 final report lists two serious adverse events in its first year: amblyopia, judged unlikely related, and a benign pituitary tumor, judged possibly related ¹⁰. The authors closed with a caution: "Long-term studies are needed to confirm these results" ⁹.

A long-term report followed ¹⁰. The 36 children could continue in an extension, receiving a new implant when the 12-month implant was removed ¹⁰. The final report, published online on March 24, 2015, covers up to 6 years of treatment and up to 1 year afterward ¹⁰. Hormonal suppression was maintained throughout, in the 16 children treated before and in the 20 new to treatment ¹⁰. Of the 36 children, 31 continued into the extension, and 22 of them received at least three implants ¹⁰.

Among the children new to treatment, the ratio of bone age to actual age fell from 1.417 at the start (20 children) to 1.18 at 48 months (8 children) ¹⁰. A ratio above 1 means the bones are older than the child. The abstract gives predicted adult height in girls as 151.9 centimeters at the start and 166.5 at month 60, the later figure resting on 6 girls ¹⁰. In 5 girls new to treatment, mean predicted adult height rose 10.7 centimeters by month 60; 1 girl treated before remained ¹⁰. Predicted heights are forecasts, not measured adult heights, and the late figures rest on 5 to 8 children ¹⁰.

The authors reported no adverse effect on growth, or on the recovery of the body's own hormone system after treatment ¹⁰. Like the first year, the extension was open-label ¹⁰.

For advanced prostate cancer, the Vantas label reports one open-label, phase 3 study of 138 men ³. Each received a single implant and was evaluated for at least 60 weeks ³. Of them, 37 had stage C disease and 29 had stage D on the Jewett scale, a staging system for prostate cancer ³. The other 72 had a raised or rising prostate-specific antigen (PSA), a blood marker of the cancer, after earlier treatment of localized disease ³. The main measure was a testosterone level of 50 nanograms per deciliter or less, the castrate level ³.

On day 28, all 134 men with a measurement had reached that level ³. Of the 120 who completed 52 weeks, 115 had a week-52 measurement, and all were at or below 50 ³. Four men (3 percent) showed breakthrough above the castrate level, one of them a value the label says was "possibly related to lab error" ³. In two of them the implant could not be found, and the label says it may have been expelled without the patient noticing ³. PSA fell to within normal limits by week 24 in 103 of 111 evaluable men (93 percent) ³.

Eighteen men left before week 52: 6 died, 5 had disease progression, 3 expelled the implant, 2 entered hospice and 2 withdrew ³. The study had no comparison group, and its measures were testosterone and PSA levels ³. The label reports no survival result for Vantas ³.

Neither label reports a study of histrelin for weight loss, muscle, aging or athletic performance ¹, ³. The Supprelin LA label says safety and effectiveness "have not been established" in children under 2 years ¹. The Vantas label says the same of females and of pediatric patients ³.

What are the side effects?

For Supprelin LA in children with CPP, the figures come from the two single-arm trials ¹. They treated 47 children, 44 girls and 3 boys, for 9 to 18 months ¹. The most common reaction was at the implant site, in 24 of the 47 (51.1 percent): "discomfort, bruising, soreness, pain, tingling, itching, implant area protrusion and swelling" ¹. Keloid scar, a raised scar, was reported in 3 children (6.4 percent), as were other scarring and suture-related complications ¹.

Two children had a serious adverse reaction ¹. One, who "coincidentally had Stargardt's Disease," an eye disease, developed amblyopia, reduced vision in an eye ¹. The other had a benign pituitary tumor ¹. One child left a study because of an infection at the implant site ¹.

The Supprelin LA label carries six warnings ¹. For the first week, as hormones rise, it warns: "Patients may experience worsening of symptoms or onset of new symptoms during this period" ¹. The implant has broken during removal in some cases, and the label reports rare "events of spontaneous extrusion of the implant," the implant working its way out ¹. Psychiatric reports with this class of drugs "include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression" ¹. Since approval, depression has also been reported, "including rare reports of suicidal ideation and attempt" ¹.

Convulsions have been reported "in patients receiving GnRH agonists, including SUPPRELIN LA," some of them in patients with no history of seizures ¹. A warning added in September 2025 covers severe skin reactions reported with GnRH agonists, among them Stevens-Johnson syndrome and toxic epidermal necrolysis ¹. The sixth warning is pseudotumor cerebri, raised pressure in the fluid around the brain, reported in children receiving GnRH agonists ¹. Its signs include headache, blurred or double vision and ringing in the ears ¹.

Supprelin LA is contraindicated, meaning it must not be used, in two groups ¹. One is patients "who are hypersensitive to gonadotropin releasing hormone (GnRH) or GnRH agonist analogs" ¹. The other is pregnancy, because the expected hormonal changes "increase the risk for pregnancy loss" ¹.

For Vantas in men with prostate cancer, the label counts possibly or probably related events in 171 men in two trials over up to 24 months ³. Hot flashes were the most common event, in 112 men (65.5 percent), and 2.3 percent of patients reported severe ones ³. Fatigue followed at 9.9 percent, implant site reaction at 5.8 percent and testicular atrophy, a shrinking of the testes, at 5.3 percent ³. The label marks hot flashes and testicular atrophy as expected consequences of testosterone suppression ³. In the first 12 months an implant came out through the incision in 8 of the 171 men ³.

The Vantas label's warnings begin with the first-week rise in testosterone ³. Patients "may experience worsening of symptoms or onset of new symptoms, including bone pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction" ³. Neuropathy is nerve damage, hematuria is blood in the urine, and the obstructions are blockages of the urinary tract. The label reports cases of spinal cord compression, "which may result in paralysis," with GnRH agonists ³.

The label also reports hyperglycemia, meaning high blood sugar, and "an increased risk of developing diabetes" in men receiving GnRH agonists ³. It reports an increased risk of heart attack, sudden cardiac death and stroke with these drugs in men ³. Of that risk it says it "appears low based on the reported odds ratios" ³. Further warnings cover severe skin reactions, a lengthening of the heart's QT interval, a measure on the heart tracing, and harm to a fetus ³.

Reports since approval include pituitary apoplexy, which the label defines as "a clinical syndrome secondary to infarction of the pituitary gland" ³. Infarction is the death of tissue whose blood supply has been cut off. They also include convulsions, suicidal ideation and attempt, and severe liver injury that "was reversible with the removal of the VANTAS implant" ³. On bone, the label says long periods of medical castration in men can be expected to affect bone density ³. The Vantas label lists hypersensitivity to GnRH or GnRH agonist analogs as a contraindication ³.

Both labels list weight changes among the reported events, and neither product's trials had a comparison arm to set them against ¹, ³. In the Supprelin LA trials, "weight increased" was reported as possibly related or related in 1 of the 47 children ¹. Among the 171 men on Vantas, weight increase was reported in 4 (2.3 percent), and "weight decreased" in fewer than 2 percent ³.

In sport

WADA, the World Anti-Doping Agency, names histrelin on its 2026 Prohibited List ¹¹. It appears in section S2.2.1, headed "Testosterone-stimulating peptides in males," in a bullet that reads: "gonadotrophin-releasing hormone (GnRH, gonadorelin) and its agonist analogues (e.g. buserelin, deslorelin, goserelin, histrelin, leuprorelin, nafarelin and triptorelin)" ¹¹. Substances in section S2 are prohibited at all times, in and out of competition, and the list classes every one of them as a non-specified substance ¹¹. Specified substances, by the list's own explanation, are those "more likely to have been consumed or used by an Athlete for a purpose other than the enhancement of sport performance" ¹¹.

What JumpstartMD offers

JumpstartMD does not prescribe histrelin. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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