Zoladex
Zoladex
Generic Name
Zoladex
Mechanism
Zoladex is a gonadotropin‑releasing hormone (GnRH) agonist.
• Binds to GnRH receptors in the anterior pituitary → sequential overstimulation of gonadotropin release (LH/FSH).
• The initial surge causes a transient rise in sex steroid production (estrogen/testosterone).
• Persistent stimulation leads to down‑regulation of pituitary GnRH receptors, resulting in suppressed LH and FSH secretion.
• Consequence: ↓ ovarian/testicular steroidogenesis → profound hypogonadism (estrogen, progesterone, testosterone fall).
• In breast and prostate cancers, this reduces estrogen and testosterone‑dependent tumor growth; in endometriosis, it reduces estrogen‑driven ectopic tissue proliferation.
Pharmacokinetics
| Parameter | Typical Value |
| Formulation | Subcutaneous depot (1 mg and 3.6 mg every 4 mo) |
| Onset of action | 1–2 weeks |
| Peak effect | 2–3 weeks after injection |
| Half‑life | 7–10 days (depot release) |
| Metabolism | Hepatic proteolytic cleavage → inactive metabolites |
| Elimination | Renal/urinary excretion (~60 % unchanged) |
| Special populations | PK unchanged in mild‑moderate hepatic impairment; dose adjustment not required in renal disease |
Indications
- Benign
- Uterine fibroids (pre‑op shrinkage)
- Endometriosis (pain, ovarian cysts)
- Pre‑operative uterine bleeding control
- Malignant
- Advanced prostate cancer (neoadjuvant, adjuvant, or palliative)
- Breast cancer – hormone‑receptor positive, menopausal women
- Advanced ovarian cancer – as adjuvant therapy with GnRH antagonists
Contraindications
- Absolute contraindications
- Known hypersensitivity to goserelin or excipients
- Pregnant/ lactating women (estrogen suppression harmful)
- Relative precautions
- Severe cardiovascular disease (angina, MI, arrhythmias) – may cause vasomotor instability
- History of seizure → seizures may be provoked by hormonal shifts
- Osteopenia/osteoporosis – risk of bone loss
- Hepatic impairment – monitor liver enzymes
Dosing
| Indication | Dose | Frequency | Administration | Notes |
| Prostate cancer (neoadjuvant/adjuvant) | 3.6 mg | Every 4 mo (sc) | Subcutaneous | Add 7.5 mg sc on day‑1 for initial flare‑control if desired |
| Breast cancer | 3.6 mg | Every 4 mo | sc | Consider oral tamoxifen concurrently |
| Endometriosis | 1.0 mg | Every 4 mo | sc | Use for ≤6 mo to limit bone loss |
| Uterine fibroids | 1.0 mg | Every 4 mo | sc | Often combined with surgical procedures |
| Adjunct to ovarian cancer | 3.6 mg | Every 4 mo | sc | Combined with chemotherapy |
*Use the lowest effective dose; switch to a depot formulation only after confirming tolerance to 1 mg.*
Adverse Effects
- Common (≥10 %)
- Hot flashes, night sweats
- Vaginal dryness / dyspareunia
- Headache, fatigue
- Mood swings / depression
- Injection site pain/erythema
- Serious (≤1 %)
- Severe bone density loss → fractures
- Cardiovascular events (myocardial infarction, stroke)
- Severe hypogonadism → infertility, reduced libido
- Severe mood disorders (suicide risk)
- Severe hepatic enzyme elevations
Monitoring
| Parameter | Frequency | Target |
| Serum LH/FSH | Baseline, 1 mo, 4 mo | Suppression to <30 % baseline |
| Sex steroids (estradiol/testosterone) | Baseline, 1 mo | <30 % baseline |
| Bone Mineral Density (DEXA) | Baseline, 12 mo, 24 mo | T‑score ≥ −1.0 |
| Liver function tests | Baseline, every 3 mo | Within normal limits |
| Cardiac assessment | Baseline, as clinically indicated | EKG if risk factors |
| Psychiatric evaluation | Baseline, every 3 mo | Mood stability |
Clinical Pearls
- Flare‑Prevention: Adding a short‑acting GnRH agonist (leuprolide 1.5 mg sc) or an anti‑androgen (bicalutamide 50 mg PO) for the first 4–6 weeks blunts the initial hormonal surge and reduces tumor‐related pain flares.
- Bone Health: Combine with calcium (1 g/d) and vitamin D (800‑1 000 IU/d) and consider bisphosphonates if BMD declines ≥ 3 % annually.
- Switching to Depot: Patients from non‑depot routes may require a transient “bridge” dose of 3.6 mg to avoid early withdrawal symptoms.
- Endometriosis Duration: Limit depot therapy to 6–12 months; beyond that, the risk of irreversible bone loss outweighs benefits.
- Compliance: A single 4‑month depot injection improves adherence versus daily oral GnRH antagonists; counsel patients on recognizing injection site reactions.
- Special Populations: In male breast cancer, note that Zoladex induces hypogonadism and may lead to gynecomastia; estrogen therapy can be considered after endocrine resistance.
Key takeaways: Zoladex, a potent GnRH agonist, remains a cornerstone for hormone‑dependent malignancies and certain benign gynecologic disorders. Optimal efficacy hinges on early flare control, vigilant bone health monitoring, and individualized dosing.