Histrelin
An FDA-approved GnRH agonist nonapeptide delivered via a once-yearly subcutaneous hydrogel implant, used for central precocious puberty (Supprelin LA) and historically for advanced prostate cancer (Vantas).
What is Histrelin?
Histrelin is a synthetic nonapeptide GnRH superagonist ([D-His(imBzl)6, Pro9-NHEt]-GnRH) that, like other GnRH agonists, suppresses the reproductive hormone axis when delivered continuously. What distinguishes histrelin from its class-mates (leuprolide, triptorelin, goserelin, buserelin, nafarelin) is its delivery system: a small non-degradable hydrogel implant — made of the same hydroxyethyl methacrylate material family as soft contact lenses — that is placed subcutaneously in the inner upper arm under local anesthesia and releases approximately 50–65 mcg per day of histrelin over a full 12 months. FDA-approved formulations are Supprelin LA (50 mg implant, 2007, for central precocious puberty) and Vantas (50 mg implant, 2004, for palliative treatment of advanced prostate cancer; Vantas was discontinued in the US market in 2021). The once-yearly implant is the defining clinical feature — it replaces 12 monthly (or 4 quarterly) depot injections with a single in-office procedure.
What Histrelin Is Investigated For
Histrelin's clinical profile is essentially the GnRH-agonist class profile — profound LH/FSH suppression, medical castration of testosterone or estrogen within 3–4 weeks, reversible after discontinuation — delivered through a once-yearly subcutaneous hydrogel implant rather than monthly or quarterly depot injections. The strongest evidence is for central precocious puberty (Supprelin LA, FDA-approved 2007), where multicenter Phase 3 trials (Eugster 2007; Silverman 2015 long-term report) demonstrated reliable suppression of peak LH and sex steroids for 12 months with a single implant, and subsequent real-world data established that a single implant often remains effective for 2–3 years — now reflected in informal practice even though the label specifies annual replacement. For advanced prostate cancer (Vantas, FDA-approved 2004), open-label registration trials showed 100% of patients achieved castrate testosterone by week 4 with maintenance through 52 weeks, and Shore et al. (2012) confirmed efficacy and tolerability across repeated annual implantations up to 4+ years. Histrelin's implant format has also made it popular for pubertal suppression in transgender and gender-diverse youth — an off-label use supported by Endocrine Society and WPATH guidelines and examined in several retrospective cohorts. The clinical tradeoffs are distinctive to the implant format: a minor in-office surgical placement and retrieval procedure, a recognized rate of implant breakage during removal (reported around 20% in long-term extension data) that occasionally requires ultrasound-guided retrieval, and cases of retained bioactive fragments producing pubertal suppression for up to 5 years after the intended removal date. Vantas was discontinued in the US in 2021 amid supply and market changes and is no longer readily available for prostate cancer; Supprelin LA remains commercially available.
History & Discovery
Histrelin itself is not a new molecule — the nonapeptide was synthesized in the late 1970s and early 1980s as part of the wave of GnRH-agonist analogs that followed Andrew Schally's Nobel-Prize-winning work on native LHRH. Early clinical studies of subcutaneous and intranasal histrelin for central precocious puberty were published in the 1980s and 1990s, demonstrating pharmacological suppression comparable to other GnRH agonists but without a clearly differentiated clinical niche. The peptide was essentially a spare member of a crowded class. The story that matters is the hydrogel implant. Hydro Med Sciences — later renamed Valera Pharmaceuticals, ultimately acquired by Indevus Pharmaceuticals and then Endo Pharmaceuticals — developed a non-degradable reservoir implant technology based on hydroxyethyl methacrylate (HEMA) hydrogels, the same polymer family used in soft contact lenses. The company loaded histrelin into a small flexible rod and demonstrated near-zero-order drug release at approximately 50–65 mcg/day for a full 12 months. This transformed histrelin from a generic class member into the only GnRH agonist deliverable as a single once-yearly placement, matching the frequency of visits that clinicians and patients actually wanted. Phase 3 development pursued two indications in parallel: advanced prostate cancer (Vantas) and central precocious puberty (Supprelin LA). Vantas was FDA-approved in October 2004 for palliative treatment of advanced prostate cancer — the first and, for years, only once-yearly GnRH agonist product. Supprelin LA followed in May 2007 for central precocious puberty in pediatric patients, with Eugster's multicenter Phase 3 trial in 36 children (published in the Journal of Clinical Endocrinology and Metabolism in 2007) providing the registration package. Both products were commercialized by Endo Pharmaceuticals. The subsequent clinical evolution has been twofold. First, extended single-implant use has become increasingly common in CPP practice — real-world cohorts (Lewis 2013, Fisher 2023, Pine-Twaddell 2023) consistently show that a single implant often suppresses the HPG axis for 24–36 months or longer, allowing reduction in the number of in-office procedures across a multi-year treatment course. Second, pubertal suppression in transgender and gender-diverse youth has emerged as a substantial off-label use since the 2010s, with Endocrine Society and WPATH guidelines endorsing GnRH agonist suppression and histrelin's once-yearly format offering practical advantages over monthly depot injections in this population. The product has also contracted. Endo Pharmaceuticals announced discontinuation of Vantas in the United States in September 2021, citing manufacturing and supply considerations rather than safety or efficacy. The approval of oral GnRH antagonist relugolix (Orgovyx, 2020) and continued availability of long-interval depot leuprolide formulations compressed Vantas's market niche. Supprelin LA remains available and is the primary context in which histrelin is prescribed in the US today.
How It Works
Histrelin is a GnRH agonist delivered through a tiny flexible implant under the skin of the upper arm. For the first couple of weeks, it stimulates the pituitary and causes a brief rise in sex hormones — then the receptors desensitize and production of LH, FSH, testosterone, and estrogen falls to castration levels. The implant slowly releases drug for a full year from a single placement, then is surgically swapped for a new one if continued therapy is needed.
Histrelin is a nonapeptide GnRH superagonist ([D-His(imBzl)6, Pro9-NHEt]-GnRH) in which a benzylated D-histidine at position 6 and an ethylamide modification at position 9 confer enhanced receptor binding affinity and resistance to enzymatic degradation relative to native GnRH. Acute administration produces robust LH and FSH release via Gq/11-coupled GnRH receptor signaling in pituitary gonadotropes; sustained continuous exposure causes receptor internalization, uncoupling from phospholipase C downstream signaling, and transcriptional downregulation of GnRHR expression. The net result is medical castration — serum testosterone <50 ng/dL (or by contemporary consensus <20 ng/dL for optimal oncologic benefit) in adult men, and suppression of stimulated LH to prepubertal levels (<4 IU/L on GnRH stimulation test) in pediatric CPP patients — typically achieved by week 3–4 after implant placement. The distinguishing feature is the delivery system: a 3 mm x 3.5 mm non-degradable hydroxyethyl methacrylate (HEMA-based) hydrogel reservoir loaded with 50 mg histrelin acetate. The hydrogel matrix absorbs water and releases histrelin by diffusion at a near-zero-order rate of approximately 50–65 mcg/day for 12 months, producing steady-state serum histrelin concentrations in the 0.1–0.5 ng/mL range with minimal peak-to-trough variation. Because the polymer does not biodegrade, the implant requires surgical removal at the end of the treatment year. Proteolytic clearance means no CYP-mediated metabolism and negligible classical drug–drug interactions at the pharmacokinetic level.
Evidence Snapshot
Human Clinical Evidence
Strong. FDA-approved for two indications based on multicenter Phase 3 registration trials: Vantas for advanced prostate cancer (2004) and Supprelin LA for central precocious puberty (2007). Long-term extension data out to 6 years for CPP and up to 4+ years for prostate cancer. Growing retrospective literature on extended single-implant use (often 2–3 years effective) and on off-label use for pubertal suppression in transgender youth.
Animal / Preclinical
Comprehensive class-level GnRH receptor pharmacology; histrelin-specific preclinical work focused on the hydrogel implant's release kinetics and biocompatibility during the Valera/Hydro Med Sciences development program in the 1990s–early 2000s.
Mechanistic Rationale
Very strong. GnRH receptor desensitization pharmacology is among the most thoroughly characterized endocrine drug mechanisms. The hydrogel implant's zero-order release kinetics and the resulting steady-state histrelin exposure have been confirmed in PK studies.
Research Gaps & Open Questions
What the current literature has not yet settled about Histrelin:
- 01Formal study of extended single-implant use beyond 12 months — real-world cohorts consistently support 24–36 month efficacy of a single implant in CPP, but the FDA label continues to specify annual replacement; prospective trials defining the optimal extended-use duration and monitoring protocol are limited.
- 02Transgender and gender-diverse youth pubertal suppression with histrelin — retrospective cohorts exist and guidelines from the Endocrine Society and WPATH endorse GnRH agonist suppression, but prospective comparative trials of histrelin implant versus leuprolide depot in this population are sparse.
- 03Management of retained implant fragments — 2025 case series documented bioactive suppression for up to 5 years after retained fragments; there is no consensus protocol for surveillance, imaging, or intervention in the retained-fragment scenario.
- 04Cardiovascular outcomes comparison — histrelin-specific cardiovascular safety data versus GnRH antagonists (degarelix, relugolix) is limited; class-level PRONOUNCE and HERO trial findings are extrapolated but not formally replicated with the implant.
- 05Optimal pubertal-suppression timing and duration in transgender adolescents — long-term bone density, neurocognitive, psychosocial, and metabolic outcomes after sustained histrelin-based pubertal suppression transitioning to gender-affirming hormones are being characterized in ongoing registry and cohort data.
- 06Future availability — Vantas was discontinued in the US in 2021; the single-product dependency on Supprelin LA (also Endo Pharmaceuticals) creates a supply-continuity concern for pediatric CPP that has not been fully addressed by alternative implant development.
Forms & Administration
Subcutaneous hydrogel implant only. 50 mg histrelin acetate loaded in a 3 mm x 3.5 mm non-degradable polymer rod. Placed in the inner aspect of the upper arm (non-dominant side) under local anesthesia as a minor in-office procedure — small incision, subcutaneous pocket, implant insertion, skin closure. Removed at the end of the treatment year (or later, if extended use is appropriate) through a similar procedure. Two commercial products: Supprelin LA (central precocious puberty, pediatric) and Vantas (advanced prostate cancer, adult; discontinued in the US market in September 2021 but historically identical 50 mg formulation). The implant is not radiopaque; if palpation or ultrasound cannot localize a difficult implant, soft-tissue ultrasound is the usual imaging approach. All implant placement and removal should be performed by a clinician trained in the procedure; never attempt self-placement or self-removal.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
Single 50 mg histrelin acetate subcutaneous implant, placed in the inner aspect of the non-dominant upper arm. Dose strength is fixed; no weight-based or response-based dose titration is possible — the implant releases histrelin at a near-constant rate of approximately 50 mcg/day (Vantas) to 65 mcg/day (Supprelin LA) over the treatment year. Dose cannot be adjusted after placement. Two commercial products share the same 50 mg loaded dose but differ in labeled indication: Supprelin LA (central precocious puberty, pediatric) and Vantas (advanced prostate cancer, adult; discontinued in the US in 2021).
Frequency
One implant per 12-month treatment year. At the end of the year, the old implant is surgically removed and a fresh implant is inserted (through a new incision, or occasionally through the same incision site) if continued therapy is appropriate. Extended single-implant use beyond 12 months is off-label but increasingly common in CPP practice, supported by published cohorts showing continued suppression at 24–36 months in most patients.
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
In central precocious puberty, therapy continues until the child reaches an age appropriate for physiologic puberty (typically ages 11–12 in girls and 12–13 in boys), at which point the implant is removed and not replaced. In advanced prostate cancer (historically, with Vantas), therapy was typically continued indefinitely for metastatic disease. For transgender pubertal suppression (off-label), duration varies based on individualized treatment planning with the patient and clinical team; therapy may transition to gender-affirming hormones when age-appropriate.
Protocol Notes
The histrelin implant is placed under local anesthesia in an outpatient clinic setting. The procedure typically takes 10–15 minutes: sterile prep of the inner upper arm, local anesthetic infiltration, a small incision (3–5 mm), subcutaneous tunnel creation with an insertion tool, implant placement, and wound closure with adhesive strips or a single suture. Removal is a similar procedure but can occasionally be more involved — the implant may become encapsulated in fibrous tissue, and the hydrogel can become brittle after a full year in situ, leading to the well-documented risk of implant fracture during retrieval. Implant breakage during removal is the signature complication of this delivery format. Long-term Phase 3 extension data in CPP patients reported a breakage rate of approximately 22% over 6 years, and subsequent real-world series report rates in the same range. When the implant fragments, retrieval of all pieces is important because retained fragments can remain bioactive — a 2025 case series documented pubertal suppression persisting for up to 5 years after retained fragments were left in place. Ultrasound localization is used when palpation fails; the implant is not radiopaque, so plain radiographs are not helpful, and MRI or high-frequency ultrasound is the usual imaging approach for difficult retrievals. The initial testosterone or gonadotropin flare characteristic of the GnRH agonist class is less of a clinical concern with histrelin in prostate cancer than with some depot agonists because the hydrogel releases drug relatively slowly during the first days after placement — the flare is attenuated, though not eliminated, and anti-androgen pre-loading (bicalutamide, flutamide) was still used by many clinicians during the Vantas era in patients with high tumor burden. In central precocious puberty, the flare is of minimal clinical concern and no routine prophylaxis is needed. Bone mineral density monitoring is appropriate for adult ADT use (historically with Vantas) and is less of an issue in the time-limited pediatric CPP indication. Cardiovascular and metabolic risks of prolonged androgen deprivation are class-level concerns that shaped the market shift toward GnRH antagonists (degarelix injectable, relugolix oral) in some high-risk patients. For pediatric CPP use, periodic monitoring of clinical pubertal progression (Tanner staging), bone age, and stimulated LH response (GnRH stimulation test or random LH measurement) guides decisions about implant replacement timing. When extending single-implant use beyond 12 months off-label, confirmation of ongoing suppression via these markers is particularly important.
Histrelin implants (Supprelin LA, Vantas) are FDA-approved specialty medications requiring placement and removal by a clinician trained in the procedure. Supprelin LA is approved for central precocious puberty in pediatric patients; Vantas was approved for advanced prostate cancer but discontinued in the US market in September 2021. Extended single-implant use beyond 12 months and off-label pubertal suppression in transgender and gender-diverse youth are common clinical uses but are not formally included in the FDA labels. This is not a self-administered peptide — never attempt implant placement, removal, or self-treatment outside a qualified clinical setting.
Timeline of Effects
Onset
After implant placement, an initial gonadotropin 'flare' of LH and FSH occurs over the first 7–14 days, with a corresponding transient rise in testosterone or estrogen. The flare is somewhat attenuated relative to depot injection formulations because the hydrogel releases drug gradually during the first days in situ rather than delivering a bolus. Pituitary desensitization develops over 2–4 weeks. In adult men with advanced prostate cancer, castrate-level testosterone (<50 ng/dL) is achieved in essentially all patients by week 3–4 — registration trial data showed 100% of evaluable patients at castrate levels by week 4. In children with central precocious puberty, stimulated LH falls to prepubertal levels (<4 IU/L on GnRH stimulation) within the first few months, with clinical markers (breast development regression or slowing, testicular volume stability, bone-age progression slowing) observable over 3–6 months.
Peak Effect
Steady-state histrelin delivery of approximately 50–65 mcg/day is maintained throughout the 12-month treatment year, with steady-state serum concentrations in the 0.1–0.5 ng/mL range. Clinical effects — castrate testosterone in adults, prepubertal LH suppression in pediatric CPP — are maintained continuously through month 12. In advanced prostate cancer, PSA typically declines through months 1–6 to a nadir prognostic of long-term outcome. In central precocious puberty, bone age progression slows toward calendar age and predicted adult height increases (Phase 3 extension data showed a mean 10.7 cm predicted adult height gain in treatment-naive CPP children over 5–6 years of therapy). Hot flashes, fatigue, and other symptom burden in adult ADT use are maximal in the first months and partially attenuate over time.
After Discontinuation
Recovery of pituitary function and gonadal hormone production after implant removal is gradual and follows the same pattern as other GnRH agonists. In adult men after extended ADT, testosterone recovery to baseline typically takes 6–12 months and may be incomplete in older men. In children with CPP, resumption of clinical pubertal progression and gonadotropin responsiveness is typically observed within 3–12 months after removal, allowing physiologically appropriate puberty to proceed. If a retained fragment is inadvertently left in place after an attempted removal, suppression can persist — documented for up to 5 years in published case reports — and clinical pubertal progression will not resume until the retained fragment is located and removed or its hormone release subsides.
Common Questions
Who Histrelin Is NOT For
- •Pregnancy — histrelin can cause fetal harm; the implant must be removed if pregnancy occurs, and effective contraception is required for patients of reproductive potential during therapy.
- •Breastfeeding — not recommended.
- •Known hypersensitivity to histrelin, GnRH, or other GnRH analogs (cross-reactivity is possible).
- •Active skin infection or compromised soft-tissue integrity at the intended implant site — insertion should be deferred until the site is suitable.
- •Severe spinal cord compression, urinary tract obstruction, or impending cord compression in advanced prostate cancer — the initial flare can worsen these conditions; anti-androgen pre-loading or alternative therapy (GnRH antagonist) should be considered.
- •Pre-existing severe osteoporosis without bone-protective co-therapy — relative contraindication for extended adult ADT; not typically a concern in time-limited pediatric CPP use.
- •Significant pre-existing cardiovascular disease — relative contraindication warranting consideration of GnRH antagonist class as an alternative in adult ADT use; class-level cardiovascular signal applies.
- •Pediatric use outside approved indication — Supprelin LA is labeled for central precocious puberty; other pediatric uses (including transgender pubertal suppression) are off-label and require specialist supervision.
- •Inability to comply with required implant removal — because the hydrogel matrix does not biodegrade and spent implants can remain bioactive, reliable follow-up for removal is essential before initiating therapy.
Drug & Supplement Interactions
Histrelin's classical drug-interaction profile is minimal because peptide proteolytic clearance does not engage CYP-mediated metabolism. The clinically relevant interactions are pharmacodynamic, and the slow-release implant format means systemic histrelin exposure is lower and more stable than with depot injections, further reducing potential for interactions. Anti-androgens (bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide): historically co-administered with Vantas in advanced prostate cancer during the flare period or as continued combined androgen blockade. The combination is intended therapy, not a problematic interaction. QT-prolonging medications: like other GnRH agonists, histrelin can prolong QT interval; combination with other QT-prolonging agents (Class IA and III antiarrhythmics, certain antiemetics, fluoroquinolones, methadone) warrants ECG monitoring and electrolyte management in at-risk adult patients. Diabetic medications: long-term adult ADT alters insulin sensitivity and increases diabetes risk; medication adjustments may be needed over months of therapy. Antihypertensives and cardiac medications: chronic androgen deprivation affects lipid profiles and cardiovascular physiology; medication adjustments may be appropriate during extended therapy. Growth hormone therapy in pediatric CPP patients: sometimes co-prescribed when short stature prognosis warrants adjunctive GH therapy in addition to pubertal suppression; the combination is intended and follows pediatric endocrinology protocols. As with any specialty medication, patients (or caregivers for pediatric patients) should disclose all prescription, OTC, and supplement use to the prescribing clinician. The implant itself cannot be 'paused' for a drug interaction — if a clinically meaningful interaction arises during the treatment year, the management options are to modify the interacting medication or to remove the histrelin implant early.
Safety Profile
Common Side Effects
Cautions
- • Initial testosterone or gonadotropin flare during first 1–2 weeks
- • Bone mineral density loss with extended use (relevant in long ADT)
- • Cardiovascular risk with prolonged androgen deprivation
- • Implant retrieval can fail or fragment, with bioactive fragments persisting for years
- • Not for use in pregnancy
- • Insertion and removal are minor surgical procedures requiring clinician skill
What We Don't Know
Well-characterized safety profile across two decades of clinical use in central precocious puberty and prostate cancer. Long-term outcomes of extended single-implant use beyond 12 months are increasingly well-documented but not formally labeled. Off-label pubertal suppression in transgender youth has growing retrospective evidence but few large prospective trials.
Legal Status
United States
Supprelin LA (histrelin acetate 50 mg subcutaneous implant) is FDA-approved (initial approval May 2007, Endo Pharmaceuticals) for the treatment of central precocious puberty in pediatric patients. Vantas (same 50 mg implant) was FDA-approved in October 2004 for palliative treatment of advanced prostate cancer but was discontinued by Endo Pharmaceuticals in the US market in September 2021 due to manufacturing and supply considerations. Supprelin LA remains commercially available as a prescription-only specialty medication distributed through specialty pharmacies. It is not a controlled substance. Insertion and removal are performed by qualified clinicians; there is no self-administered version of histrelin.
International
Supprelin LA is approved in several international markets for central precocious puberty. Vantas was approved and marketed in various markets globally for advanced prostate cancer but has been withdrawn or discontinued in many of these markets in parallel with the US discontinuation. International availability of the histrelin implant for pediatric CPP use continues in major markets; for prostate cancer, patients have largely transitioned to leuprolide, triptorelin, goserelin, degarelix, or relugolix.
Sports & Competition
Histrelin, like all GnRH agonists, is listed on the WADA Prohibited List under S4 (Hormone and Metabolic Modulators) and is prohibited at all times for male athletes outside of Therapeutic Use Exemption. The implant format makes non-therapeutic 'PCT' use in bodybuilding or enhanced athletics contexts impractical compared with injectable or oral formulations, but the regulatory status is identical: legitimate therapeutic use under TUE is permitted; any non-therapeutic use is prohibited.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
The histrelin implant is just 'leuprolide in an implant' — the drug doesn't matter, only the delivery.
Reality
Histrelin is a distinct nonapeptide GnRH superagonist with its own structure (benzyl-D-histidine at position 6, ethylamide at position 9) and receptor-binding profile. Pharmacologically and clinically, the effects on the GnRH receptor, pituitary desensitization, and gonadal suppression are essentially equivalent to leuprolide or triptorelin — selection between agents is driven by formulation and delivery rather than meaningful efficacy differences. The once-yearly hydrogel implant is the distinguishing clinical feature, not a different drug mechanism.
Myth
Once placed, the implant is effective forever — removal is optional.
Reality
The hydrogel matrix releases histrelin for approximately 12 months at therapeutic rates, then release tapers. By the end of the treatment year, the implant is pharmacologically 'spent' but the polymer does not biodegrade — the physical implant remains in place until surgically removed. Leaving a spent implant indefinitely is not dangerous in the majority of cases (it becomes an inert fibrotic subcutaneous rod), but retained fragments after breakage can remain bioactive and suppress the HPG axis for years in some patients. Published protocol is annual removal and replacement; extended use up to 2–3 years is supported by real-world data but should be clinician-supervised.
Myth
The histrelin implant is inserted once and then forgotten — no procedures needed after that.
Reality
At minimum, therapy requires one placement procedure and one removal procedure per treatment year. Continuing therapy beyond a year involves a removal-and-replacement procedure at each annual visit. Implant breakage during removal is a recognized complication (roughly 20% in long-term extension data), and difficult retrievals can require ultrasound guidance. Any patient or family considering the implant should understand the procedural cadence, not just the between-visit convenience.
Myth
Vantas was discontinued because it was found to be unsafe for prostate cancer.
Reality
Endo Pharmaceuticals discontinued Vantas in the US market in September 2021 for manufacturing and supply reasons, not for safety or efficacy. The clinical profile — sustained castrate testosterone across annual implant cycles, well-characterized side effects consistent with the GnRH agonist class — was not a factor in the discontinuation decision. The same 50 mg histrelin implant remains available as Supprelin LA for central precocious puberty.
Myth
The implant causes permanent loss of reproductive or pubertal function.
Reality
Histrelin's effects are reversible, like those of other GnRH agonists. In children with CPP, pubertal progression resumes within months of implant removal and adult fertility outcomes after pediatric GnRH agonist therapy are well-documented. In adult men after extended ADT with Vantas (historically), testosterone recovery is gradual (6–12 months or longer) and may be incomplete in older men after multi-year ADT — but this is a class-level concern, not unique to the implant format. In transgender youth using histrelin for pubertal suppression (off-label), endogenous pubertal progression is expected to resume after removal if gender-affirming hormones are not initiated.
Published Research
24 studiesProlonged Pubertal Suppression due to Retained Histrelin Implant in Three Children with Central Precocious Puberty
Recent case series showing that retained implant fragments after breakage during removal can remain bioactive and suppress the HPG axis for up to 5 years — important safety signal for the implant format.
Extended Use of Histrelin Implant in Pediatric Patients
Long-term experience with the use of a single histrelin implant beyond one year in patients with central precocious puberty
Histrelin Implants for Suppression of Puberty in Youth with Gender Dysphoria: A Comparison of 50 mcg/Day (Vantas) and 65 mcg/Day (SupprelinLA)
Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial
Silverman et al. final Phase 3 extension report — 6-year follow-up of annual histrelin implant replacement in CPP patients, with predicted adult height gain and sustained pituitary suppression.
Long-term efficacy and tolerability of abdominal once-yearly histrelin acetate subcutaneous implants in patients with advanced prostate cancer
A single histrelin implant is effective for 2 years for treatment of central precocious puberty
Lewis et al. — prospective study demonstrating that a single histrelin implant left in place for 24 months maintains equivalent LH suppression at months 12 and 24, establishing the evidence base for extended single-implant use in CPP.
Random luteinizing hormone often remains pubertal in children treated with the histrelin implant for central precocious puberty
Long-term efficacy and tolerability of once-yearly histrelin acetate subcutaneous implant in patients with advanced prostate cancer
Shore et al. — multi-year extension of annual implant replacement in prostate cancer patients, confirming sustained castrate testosterone across repeated treatment cycles out to 4+ years.
Analysis of testosterone suppression in men receiving histrelin, a novel GnRH agonist for the treatment of prostate cancer
Histrelin: in advanced prostate cancer
Results of a second year of therapy with the 12-month histrelin implant for the treatment of central precocious puberty
A review of the pharmacokinetic and pharmacological properties of a once-yearly administered histrelin acetate implant in the treatment of prostate cancer
Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial
Eugster et al. multicenter Phase 3 trial supporting the 2007 FDA approval of Supprelin LA — 36 children, all achieved and maintained prepubertal LH and sex steroid suppression at 12 months.
Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer
Open-label multicenter Phase 3 registration trial (Schlegel) supporting the 2004 FDA approval of Vantas — 100% of evaluable patients achieved castrate testosterone by week 4, maintained through 52 weeks.
The histrelin implant: a novel treatment for central precocious puberty
First-in-class pediatric report (Hirsch et al.) of the 50 mg histrelin subcutaneous implant in children with CPP — demonstrating full-year suppression and paving the way for the Supprelin LA FDA submission.
An evaluation of the pharmacokinetics and pharmacodynamics of the histrelin implant for the palliative treatment of prostate cancer
Histrelin Hydrogel Implant--Valera: Histrelin implant, LHRH-Hydrogel implant, RL 0903, SPD 424
Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin
Early proof-of-concept trial establishing that a single subcutaneous histrelin hydrogel implant maintains castrate testosterone levels for a full year in advanced prostate cancer — the foundation for the Vantas program.
An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer
Histrelin. A review of its pharmacological properties and therapeutic role in central precocious puberty
Foundational pharmacological review of histrelin as a GnRH superagonist, predating the hydrogel implant, establishing the peptide's receptor affinity and suppressive profile in pediatric use.
Experience with the once-yearly histrelin (GnRHa) subcutaneous implant in the treatment of central precocious puberty
Gonadotropin Releasing Hormone (GnRH) Analogues
Histrelin - LiverTox: Clinical and Research Information on Drug-Induced Liver Injury
Quick Facts
- Class
- GnRH Agonist
- Evidence
- Strong
- Safety
- Well-Studied
- Updated
- Apr 2026
- Citations
- 24PubMed
Also known as
Tags
Related Goals
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.