What is Zoladex?
Zoladex (goserelin acetate) is a synthetic gonadotropin-releasing hormone (GnRH) agonist administered as a biodegradable subcutaneous depot implant that suppresses sex hormone production by inhibiting pituitary gonadotropin secretion, primarily used for treating hormone-sensitive cancers and certain benign hormone-dependent conditions. 1
Mechanism of Action
Goserelin functions as a GnRH analogue that initially stimulates, then chronically suppresses pituitary gonadotropin release 1, 2. After the first injection, there is a transient increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormones (testosterone in males, estradiol in females) 1, 3, 4. With continued administration, sustained suppression occurs, reducing testosterone to castrate levels in men within 2-4 weeks and estradiol to menopausal levels in women 1, 3, 4.
Formulation and Administration
Zoladex is supplied as a sterile, biodegradable implant containing 3.6 mg of goserelin (equivalent to 3.8 mg goserelin acetate) dispersed in a D,L-lactic and glycolic acids copolymer matrix. 1 The implant is:
- Preloaded in a single-use syringe with a 16-gauge needle 1
- Administered subcutaneously every 28 days 1, 3
- Designed for continuous release at approximately 120 mcg/day over 4 weeks 2
- A longer-acting 10.8 mg formulation exists for 3-month administration 5, 4
The copolymer matrix is completely biodegradable with no antigenic potential 1.
Clinical Indications
Prostate Cancer
Goserelin produces partial disease remission or stabilization in approximately 75% of men with previously untreated advanced prostate cancer, with efficacy equivalent to orchidectomy or diethylstilbestrol 2, 3. Multiple randomized trials demonstrated that goserelin combined with radiation therapy significantly improved disease-free survival and reduced prostate cancer-specific mortality compared to radiation alone 6.
Breast Cancer
In premenopausal women with hormone-sensitive breast cancer, goserelin achieves objective response rates of 30-45%, suggesting comparability to surgical ovariectomy 2, 7. When combined with anastrozole, zoledronic acid prevented bone loss in the lumbar spine and hip regardless of endocrine therapy (P < 0.0001) 6.
Benign Gynecological Conditions
Goserelin effectively treats endometriosis and aids surgical removal of uterine leiomyomas by reducing fibroid size and blood loss 2. It has also been used successfully in treating central precocious puberty in girls when administered every 9-12 weeks 5.
Pharmacokinetics
When administered as a solution, goserelin is rapidly absorbed with a mean elimination half-life of 4.2 hours in males and 2.3 hours in females 4. The depot formulation's serum profile is determined by the rate of drug release from the biodegradable matrix over 1 or 3 months 4.
No dose adjustment is required in elderly patients or those with hepatic impairment. 1 In severe renal impairment (creatinine clearance < 20 mL/min), the elimination half-life increases to 12.1 hours, but pharmacokinetic studies indicate no dose adjustment is needed with the depot formulation 1, 4.
Important Adverse Effects and Precautions
Tumor Flare
The initial testosterone elevation can cause disease "flare" in 17% of men with prostate cancer, including potential spinal cord compression within the first week of therapy. 3 This represents a critical early complication requiring vigilant monitoring.
Bone Loss
Gonadotropin-releasing hormone agonists cause 2- to 10-fold higher yearly bone loss compared to healthy age-matched populations 6. Patients receiving goserelin should receive vitamin D3 and calcium supplementation, with bisphosphonate therapy considered for those with additional risk factors (T-score ≤-1.5, age >65, corticosteroid use >6 months, family history of hip fracture, or personal fragility fracture after age 50). 6
Common Side Effects
Hot flushes and loss of libido occur in most patients due to sex steroid suppression 2. The medication is generally better tolerated than diethylstilbestrol in prostate cancer and associated with less acute toxicity than cytotoxic chemotherapy in breast cancer 2, 7.
Contraindications
Goserelin is contraindicated in pregnancy, as animal studies demonstrated increased preimplantation loss, resorptions, and umbilical hernias in offspring 1. It should not be used in nursing mothers, as excretion in human milk is unknown but occurs in lactating rats 1.