Histrelin
Description
Chemical and Pharmacological Profile
Chemical Structure and Properties
Histrelin (C₇₀H₉₄N₁₈O₁₆) is a decapeptide analog of endogenous GnRH, with a molecular weight of 1,443.63 g/mol. It is formulated as histrelin acetate in non-biodegradable hydrogel polymer implants for sustained release .
Mechanism of Action
Histrelin binds to GnRH receptors on pituitary gonadotropes, initially stimulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Prolonged use induces receptor downregulation, suppressing LH/FSH and subsequent sex steroid production (testosterone in males, estrogen in females) .
| Parameter | Value | Source |
|---|---|---|
| Molecular Weight | 1,443.63 g/mol | |
| Average Volume of Distribution (Vd) | 58.3 ± 7.86 L | |
| Terminal Half-Life | ~3.92 hours (subcutaneous bolus) |
Therapeutic Applications
Central Precocious Puberty (CPP)
Histrelin implants slow growth velocity and delay secondary sexual characteristics in children with CPP. Long-term use improves predicted adult height by suppressing LH/FSH and sex steroids .
Advanced Prostate Cancer
Reduces testosterone to castration levels (<50 ng/dL) within 2–4 weeks, inhibiting prostate cancer progression. Clinical trials show sustained suppression for ≥52 weeks .
Pubertal Suppression in TG/NB Youth
Effective for up to 37.5 months in maintaining biochemical and clinical suppression, with rare escape events .
Pharmacokinetics and Metabolism
Metabolism
Histrelin undergoes C-terminal dealkylation and peptide hydrolysis in human hepatocytes. Renal excretion is the primary clearance route (apparent clearance: 174–179 mL/min) .
Key Kinetic Parameters
| Parameter | Value | Source |
|---|---|---|
| Apparent Clearance | 174 ± 56.5 mL/min (prostate cancer) | |
| Protein Binding | 29.5% ± 8.9% | |
| Metabolites | C-terminal dealkylation products |
Efficacy in Clinical Trials
CPP Treatment
A Phase 3 trial (n=36) demonstrated LH suppression to prepubertal levels within 1 month, with sustained efficacy for up to 72 months in long-term extensions .
Prostate Cancer
A multicenter trial (n=138) achieved testosterone suppression to <50 ng/dL by week 4, with 93% of patients showing normalized prostate-specific antigen (PSA) by week 24 .
Extended Use and Longevity
Beyond 12 Months
Retrospective studies report efficacy for up to 65 months in TG/NB youth and CPP patients. Escape from suppression occurs in ~16% of cases, often requiring dose adjustment .
Prolonged Bioactivity
Case reports describe retained implant fragments causing suppression for 5–7 years, necessitating surgical removal .
Case Studies and Rare Outcomes
Retained Implant Fragments
Three cases of CPP patients retained implant fragments post-extraction, sustaining suppression for 5–6 years until surgical removal .
7-Year Suppression
A single case reported continuous LH/FSH suppression for 7 years post-implantation without replacement .
Product Specs
Product Science Overview
Histrelin is a synthetic peptide that mimics the natural gonadotropin-releasing hormone. Its chemical formula is C66H86N18O12, and it has a molar mass of approximately 1323.528 g/mol . The structure of histrelin allows it to bind effectively to GnRH receptors, leading to its potent biological effects.
When histrelin is present in the bloodstream, it acts on specific cells in the pituitary gland known as gonadotropes. It stimulates these cells to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Over time, continuous stimulation by histrelin leads to a downregulation of GnRH receptors, resulting in decreased production of LH and FSH. This mechanism makes histrelin an effective GnRH agonist .
Histrelin is used to treat various hormone-sensitive conditions:
- Prostate Cancer: Histrelin is used in the palliative treatment of advanced prostate cancer. It helps reduce testosterone levels, which can slow the growth of prostate cancer cells .
- Central Precocious Puberty (CPP): Histrelin is effective in treating CPP in children. It helps delay the onset of puberty by reducing the levels of sex hormones .
- Uterine Fibroids: In women, histrelin can be used to manage uterine fibroids by reducing estrogen levels .
- Transgender Youth: Histrelin is sometimes used off-label to suppress puberty in transgender children and adolescents until they are ready to begin cross-sex hormone therapy .
