Introduction
Goserelin is a synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH) used as a long-acting implant formulation. It belongs to the class of GnRH agonists and is primarily used for its endocrine effects in various hormone-sensitive conditions. Marketed under the brand name Zoladex, it is available as a subcutaneous implant that provides sustained drug release over specified periods.
Mechanism of Action
Goserelin acts as a GnRH superagonist. Initially, it stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), causing a transient increase in sex hormone production ("flare effect"). With continuous administration, it downregulates GnRH receptors in the pituitary, leading to profound suppression of LH and FSH secretion. This results in significantly reduced production of estrogen in females and testosterone in males, creating a medical castration state.
Indications
- Advanced prostate cancer (hormonal treatment)
- Breast cancer in pre- and perimenopausal women
- Endometriosis (management of symptoms)
- Endometrial thinning prior to endometrial ablation for dysfunctional uterine bleeding
- Advanced ovarian cancer (palliative treatment)
- Precocious puberty (in some formulations)
Dosage and Administration
Standard dosing: 3.6 mg subcutaneous implant every 28 days or 10.8 mg implant every 12 weeks Administration:- Administered as a subcutaneous implant in the upper abdominal wall
- Use proper aseptic technique
- Rotate injection sites
- The implant is preloaded in a special syringe applicator
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No specific recommendations
- Elderly: No dosage adjustment required
- Pediatrics: Safety and effectiveness not established for most indications
Pharmacokinetics
Absorption: Slowly absorbed from subcutaneous implant; reaches peak concentrations in 12-15 days Distribution: Volume of distribution approximately 44.1 L; 27% bound to plasma proteins Metabolism: Undergoes hydrolysis of C-terminal amino acids Elimination: Half-life approximately 4-5 hours; clearance approximately 163 mL/min Excretion: Primarily renal (90% within 12 days), with 20% as unchanged drugContraindications
- Hypersensitivity to goserelin, other GnRH analogs, or implant components
- Pregnancy (Category D) and breastfeeding
- Undiagnosed abnormal vaginal bleeding
- Women who may become pregnant during therapy
Warnings and Precautions
- Initial tumor flare in prostate cancer patients may worsen symptoms temporarily
- Decreased bone mineral density with long-term use; consider calcium/vitamin D supplementation
- Increased risk of myocardial infarction, sudden cardiac death, and stroke in men
- Hyperglycemia and diabetes reported in men receiving GnRH agonists
- QT interval prolongation reported
- Depression and emotional lability may occur
- Spinal cord compression and urinary obstruction risk in prostate cancer patients
- Ovarian cysts may develop and rupture during treatment
Drug Interactions
- Other hormone therapies: May alter expected endocrine effects
- Drugs that prolong QT interval: Increased risk of torsades de pointes
- Corticosteroids: May alter metabolism of both drugs
- Warfarin: Monitor INR closely as hormonal changes may affect coagulation
Adverse Effects
Common (>10%):- Hot flashes (57-80%)
- Sexual dysfunction (decreased libido, impotence)
- Sweating
- Gynecomastia/breast tenderness
- Headache
- Emotional lability/depression
- Injection site reactions
- Myocardial infarction
- Cerebrovascular accident
- Spinal cord compression
- Severe allergic reactions
- Osteoporosis fractures
- Pituitary apoplexy
- Severe hypertension
Monitoring Parameters
- Serum testosterone levels (in prostate cancer)
- Serum estrogen levels (in breast cancer)
- Bone mineral density (baseline and periodically)
- PSA levels (prostate cancer patients)
- Liver function tests
- Lipid profile
- Blood glucose/HbA1c
- Blood pressure
- Signs of spinal cord compression
- Mood changes/depression screening
- Injection site reactions
Patient Education
- Explain the initial "flare phenomenon" and temporary symptom worsening
- Discuss expected hormonal side effects (hot flashes, sexual dysfunction)
- Emphasize importance of adherence to dosing schedule
- Instruct on proper injection site care and recognition of infection signs
- Discuss bone health and importance of calcium/vitamin D supplementation
- Advise about potential mood changes and when to seek help
- Counsel on contraception requirements during and after treatment
- Inform about increased cardiovascular risk factors
- Discuss management strategies for hot flashes and other side effects
- Explain that fertility may be affected during treatment
References
1. FDA Prescribing Information: Zoladex (goserelin acetate implant) 2. National Comprehensive Cancer Network (NCCN) Guidelines 3. Micromedex Drug Information: Goserelin 4. Lexicomp Online: Goserelin monograph 5. Schroder FH, et al. Gonadotropin-releasing hormone antagonists in prostate cancer. N Engl J Med. 2010 6. Sharifi N, et al. Androgen deprivation therapy for prostate cancer. JAMA. 2005 7. Taylor CW, et al. Long-term follow-up of gonadotropin-releasing hormone analog treatment for recurrent ovarian cancer. J Clin Oncol. 2006 8. American Society of Clinical Oncology (ASCO) Guidelines 9. European Association of Urology (EAU) Guidelines 10. Product monograph: Zoladex (goserelin acetate). AstraZeneca Pharmaceuticals