Goserelin (Zoladex)
Goserelin acetate ([D-Ser(But)6, Azgly10]-LHRH)
FDA-approved synthetic decapeptide GnRH agonist marketed as Zoladex, used for prostate cancer, breast cancer, endometriosis, and endometrial thinning via sustained suppression of gonadal steroid production (PMID 1709853, FDA label NDC 70720-950-36).
Last updated: 2026-03-10
Safety Summary
The adverse effect profile is primarily driven by the expected consequences of gonadal steroid deprivation. In men with prostate cancer, hot flashes (62%), sexual dysfunction (21%), and decreased erections (18%) are most common (FDA label, n=242). In women treated for breast cancer, hot flashes occurred in 70-76% and decreased libido in 47.7% (FDA label). For endometriosis, hot flushes (96%), vaginitis (75%), headache (75%), emotional lability (60%), and depression (54%) were reported (FDA label, n=411). Bone mineral density decreases by approximately 4.3% at the vertebral spine after 6 months of treatment in women, with partial recovery (to 2.4-2.5% loss vs baseline) 6-12 months post-treatment (FDA label). HRT add-back can mitigate bone loss without compromising efficacy (FDA label). Injection site vascular injury has been reported, including hemorrhagic shock requiring transfusion (FDA label). The 16-gauge needle of the standard implant causes more discomfort than typical injections; a reformulated microsphere version (LY01005) using a 21-gauge needle showed 0% injection-site reactions vs 1.4% for the standard implant (PMID 37010251, PMID 36895949). Cardiovascular safety data from the ISACS registry showed no significant left ventricular dysfunction after one year of goserelin plus tamoxifen (PMID 39860490). Long-term use in men is associated with increased risks of diabetes and cardiovascular disease including MI, sudden cardiac death, and stroke (FDA label).
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Who Should NOT Use This
Anaphylactic reactions reported. FDA label section 4.1.
Goserelin can cause fetal harm and increases risk of pregnancy loss. Use nonhormonal contraception during treatment and for 12 weeks after. FDA label sections 4.2, 8.1.
A woman should not begin Zoladex treatment if she has undiagnosed abnormal vaginal bleeding. FDA label section 17.3.
Risk of pituitary apoplexy, including within the first hour of administration. FDA label section 6.10.
Testosterone flare may worsen symptoms. Close monitoring required during first month; appropriate treatment should precede goserelin initiation. FDA label section 5.2.
Risk of hypercalcemia after initiating treatment, requiring monitoring. FDA label section 5.5.
Androgen deprivation therapy may prolong QT/QTc interval. FDA label section 5.9.
Increased risk of injection site hemorrhage, including hemorrhagic shock. FDA label section 5.10.
Extra care needed during injection due to risk of penetrating muscle or peritoneum. FDA label section 5.10.
GnRH agonists associated with hyperglycemia and increased diabetes risk. Monitor blood glucose and HbA1c periodically. FDA label section 5.3.
BMD loss occurs and retreatment safety data for benign gynecologic use are unavailable. Careful risk-benefit review needed. FDA label.
Depression may occur or worsen during treatment with GnRH agonists. Postmarketing reports include suicidal ideation and attempt. Monitor carefully. FDA label sections 5.11, 6.10.
Talk to Your Doctor
Before considering Goserelin (Zoladex), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-15]
Evidence Assessment
Goserelin is FDA-approved for five distinct indications based on multiple Phase 3 RCTs. The prostate cancer indication is supported by the Bolla et al. NEJM trial (n=415, PMID 9233866), the Phase III LY01005 comparator trial (n=290, PMID 37010251), and ZOLADEX vs orchiectomy trials (n=496, FDA label). Breast cancer evidence includes the ZIPP trial (n=2706), ASTRRA trial (n=1282), ABCSG Trial 5 (n=1034), INT 0101 (n=1503), and MONALEESA-7 (n=672, PMID 34965945), comprehensively reviewed in a 2025 systematic review (PMID 39975513). The POEMS trial (PMID 25738668, n=257) supports ovarian function preservation. Endometriosis data comes from controlled trials vs danazol (n=411 ZOLADEX, n=207 danazol, FDA label). This represents the highest level of clinical evidence with regulatory approval across multiple countries for decades.
1Efficacy of goserelin in ovarian function suppression and preservation for pre- and perimenopausal breast cancer patients: a systematic reviewPMID 39975513
Chen JW, Slamon S, Obi N, Mudenda R, Cosenza J, Levy MH, Citron N, Barker D, Kwok H - Therapeutic Advances in Medical Oncology (2025) - Systematic review - 29 studies included from 1742 records screened
Addition of goserelin to endocrine therapy generally improved DFS and OS in OFS setting. ZIPP (n=2706): 12-year OS 77% vs 72% (HR 0.83, p=0.013). ASTRRA (n=1282): 8-year DFS 85% vs 80% (HR 0.67, p=0.003). For OFP, goserelin+chemotherapy reduced 2-year ovarian failure (8% vs 22%, p=0.02, POEMS) and increased 5-year pregnancy rates (23% vs 12%, p=0.03). AMH recovery higher with goserelin (47-50%) vs without (22-33%). Benefits most substantial in women <=40 years.
Limitations: Systematic review without formal meta-analysis. Included studies had heterogeneous populations, endpoints, and goserelin durations. Publication bias not formally assessed.
2Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelinPMID 9233866
Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Gil T, Collette L, Pierart M - The New England Journal of Medicine (1997) - RCT (Phase 3) - 415
5-year overall survival: 79% (combined treatment) vs 62% (radiotherapy alone), p=0.001. Disease-free survival at 5 years: 85% vs 48%, p<0.001. Goserelin 3.6 mg Q4W for 3 years starting on first day of irradiation, with cyproterone acetate flare protection.
Limitations: Open-label study. Median follow-up 45 months. Optimal duration of goserelin therapy not established by this trial alone.
3Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trialNCT04563936PMID 37010251
Gu WJ et al. - Chinese Medical Journal (2023) - Phase III RCT (non-inferiority) - 290
Day-29 testosterone <=50 ng/dL: 100% goserelin, 99.3% LY01005 (non-inferior). Cumulative castration maintenance days 29-85: 97.8% goserelin, 99.3% LY01005. Mean LH decreased 98.0%, FSH decreased 64.7%, PSA decreased 96.8% in goserelin arm. LY01005 associated with fewer injection-site reactions (0% vs 1.4%).
Limitations: Open-label. Chinese population only. Manufacturer-funded (Shandong Luye Pharmaceutical). 85-day follow-up only. LY01005 uses intramuscular route vs subcutaneous for standard goserelin.
4Goserelin for Ovarian Protection during Breast-Cancer Adjuvant ChemotherapyNCT00068601PMID 25738668
Moore HCF, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partridge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens FL Jr, Gelber RD, Hortobagyi GN, Albain KS - The New England Journal of Medicine (2015) - Phase 3 RCT (POEMS/SWOG S0230) - 257
In ER-negative early breast cancer: 2-year ovarian failure 8% goserelin vs 22% chemotherapy alone (p=0.02). 2-year pregnancy rates: 21% vs 11% (p=0.03). 4-year DFS: 89% vs 78% (HR 0.49, p=0.04). 4-year OS: 92% vs 82% (HR 0.43, p=0.05).
Limitations: Closed early after interim analysis. ER-negative patients only. Small sample size for survival endpoints. Cannot fully separate ovarian protection effect from potential direct antitumor effect.
5Pharmacological and toxicological studies of a novel goserelin acetate extended-release microspheres in ratsPMID 36895949
LY01005 study group - Frontiers in Pharmacology (2023) - Animal study (pharmacology/toxicology) - Multiple cohorts of rats
LY01005 showed comparable potency to Zoladex but more sustained testosterone suppression in rats. Relative bioavailability 101% vs Zoladex. Plasma detectable for 28 days (vs 24 for Zoladex). Toxicity findings all related to known pharmacological effects. 21-gauge needle formulation.
Limitations: Animal study in rats only; clinical translation via PMID 37010251. Funded by Luye Pharmaceutical (manufacturer of LY01005).
6Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer (MONALEESA-7)NCT02278120PMID 34965945
Tripathy D et al. - Clinical Cancer Research (2022) - RCT (Phase 3, exploratory OS analysis) - 672
All patients received goserelin 3.6 mg Q4W as backbone. Median OS: 58.7 months ribociclib vs 48.0 months placebo (HR 0.76; 95% CI 0.61-0.96). In patients <40 years: median OS 51.3 vs 40.5 months (HR 0.65). Goserelin achieved estradiol suppression below detectable limits in 92-96% of patients. Longest median follow-up (53.5 months) for any CDK4/6 inhibitor trial in premenopausal patients.
Limitations: Exploratory analysis. Open-label after unblinding. 15 patients crossed over. Goserelin used as backbone in both arms, so cannot assess goserelin's independent contribution.
7Protective effect of goserelin on ovarian reserve during (neo)adjuvant chemotherapy in young breast cancer patients: a prospective cohort study in ChinaNCT02430103PMID 33411897
Wang S, Pei L, Hu T, Jia M, Wang S - Human Reproduction (2021) - Prospective cohort study - 242
AMH recovery rate at 1 year: 46.5% goserelin vs 21.8% control (OR 3.08; p=0.002). AFC and FSH recovery trends consistent. AMH levels remained low in 41.3% of patients whose menstruation had resumed, highlighting that menses resumption does not equal fertility preservation.
Limitations: Non-randomized. Selection bias despite propensity score weighting. Partly AstraZeneca-funded. Single-center Chinese population.
8Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancerNCT00827307PMID 23860520
Zhong Q et al. - British Journal of Cancer (2013) - RCT - 110
Goserelin+tamoxifen significantly reduced estradiol (p=0.002), breast density (p=0.015), and endometrial thickness (p<0.001) vs tamoxifen alone. Blocked tamoxifen-induced endometrial thickening. No significant difference in blood lipids.
Limitations: Small sample size (n=103 analyzed). Short follow-up (3 years). Single-center Chinese population.
9Goserelin: a review of its use in the treatment of early breast cancer in premenopausal and perimenopausal womenPMID 16392882
Cheer SM et al. - Drugs (2005) - Review - N/A
Adjuvant goserelin monotherapy had similar efficacy to adjuvant chemotherapy in pre/perimenopausal women with early HR+ breast cancer. Addition of goserelin to chemotherapy offered advantage in younger patients. Fewer patients amenorrheic after goserelin vs chemotherapy.
Limitations: Review article; no new primary data. Published 2005; predates ASTRRA, SOFT/TEXT, MONALEESA-7.
10Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical use in sex hormone-related conditionsPMID 1709853
Chrisp P, Goa KL - Drugs (1991) - Review - N/A
Foundational review establishing goserelin's pharmacological profile. Documented GnRH receptor downregulation mechanism, initial flare, sustained suppression. Elimination half-life ~4.2h (males), ~2.3h (females).
Limitations: Early review (1991); predates most Phase 3 data.
11Anticancer-Drug-Related Cardiotoxicity from Adjuvant Goserelin and Tamoxifen TherapyNCT01218776PMID 39860490
ISACS registry group - Journal of Clinical Medicine (2025) - Observational (registry, IPTW analysis) - 190
One year of goserelin+tamoxifen did not significantly affect mean LV function vs controls. Mean LVEF reduction similar (1.03% vs 1.16%, p=0.73). No significant association with low LV function (RR 1.75; 95% CI 0.71-4.31).
Limitations: Small sample. Observational design. Only 1-year follow-up. All White patients. Routine echo only.
12Apalutamide and Goserelin for Androgen Receptor-Positive Salivary Gland Carcinoma: A Phase II Nonrandomized Clinical Trial, YATAGARASUPMID 38940667
Honma Y et al. - Clinical Cancer Research (2024) - Phase II single-arm clinical trial - 31
Confirmed ORR 25.0% (6/24; 95% CI 9.8-46.7%). Clinical benefit rate 50.0%. Median PFS 7.4 months. In AR>=70% with no prior systemic therapy: ORR 54.5% (6/11). Did not meet predefined efficacy criteria overall, but clinically meaningful in selected subset.
Limitations: Small sample (n=31). Single-arm, non-randomized. Did not meet primary efficacy endpoint. Novel indication.
13Comparison of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancerPMID 36781519
Kim SE et al. - Breast Cancer Research and Treatment (2023) - Prospective comparative study - 193
Menstruation resumption at 12 months: 94.4% goserelin vs 95.3% leuprorelin (NS). AMH>=1 ng/mL at 12 months: 49.5% goserelin vs 44.2% leuprorelin (NS). Goserelin and leuprorelin are comparable for ovarian protection.
Limitations: Non-randomized. Only 12-month follow-up. Single-center Korean population.
14Degarelix versus goserelin (+ antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: results from a phase IIIb studyNCT00831233PMID 23258223
Anderson J, Al-Ali G, Wirth M, Gual JB, Gomez Veiga F, Colli E, van der Meulen E, Persson BE - Urologia Internationalis (2013) - Phase IIIb RCT - 40
Degarelix non-inferior to goserelin+bicalutamide for LUTS relief at 12 weeks. Per-protocol: significantly greater IPSS reduction with degarelix (p=0.04). QoL improvement: 85% degarelix vs 46% goserelin+bicalutamide (p=0.01). Prostate size reduction: 42% degarelix vs 25% goserelin+bicalutamide (p=0.04).
Limitations: Very small sample (n=40). Stopped early. Unbalanced allocation (27 vs 13).
15Gonadal steroid-dependent effects on bone turnover and bone mineral density in menNCT00114114PMID 26901812
Finkelstein JS et al. - Journal of Clinical Investigation (2016) - RCT - 437
Goserelin used to suppress endogenous steroid production in healthy men. E2 levels above 10 pg/mL and testosterone above 200 ng/dL sufficient to prevent bone resorption increases and BMD decreases. Estrogens primarily regulate bone homeostasis in adult men.
Limitations: Used goserelin as investigational tool. 16-week study only. Healthy young men (20-50). Funded in part by AstraZeneca.