Goserelin

證據等級: L5

預測適應症: 3 個

Goserelin: From Hormone-Dependent Cancers to Amenorrhea

One-Sentence Summary

Goserelin is a GnRH (gonadotropin-releasing hormone) agonist widely used internationally for the treatment of hormone-dependent conditions such as prostate cancer, breast cancer, and endometriosis. The TxGNN model predicts it may be effective for Amenorrhea, with 7 clinical trials and 19 publications currently supporting this direction — notably, inducing amenorrhea is already a well-established pharmacological effect of this drug.

Quick Overview

Item	Content
Original Indication	Not registered in the Philippines; internationally approved for prostate cancer, breast cancer, endometriosis
Predicted New Indication	Amenorrhea (disease)
TxGNN Prediction Score	99.99%
Evidence Level	L1
Philippines Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Goserelin is a synthetic GnRH agonist. When administered continuously (e.g., as a depot injection), it causes downregulation of GnRH receptors in the anterior pituitary gland. This leads to a sustained suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, which in turn inhibits ovarian estrogen production in women. The direct pharmacological consequence of this hormonal suppression is the induction of amenorrhea — the cessation of menstruation.

This prediction is notable because amenorrhea is not merely a side effect but a well-characterised and intentionally leveraged pharmacological action of goserelin. In clinical oncology, goserelin is routinely administered to premenopausal breast cancer patients to achieve ovarian suppression, with amenorrhea serving as the clinical indicator of successful treatment. Multiple Phase 3 trials (e.g., OPTION trial, SWOG S0230) have specifically measured amenorrhea rates as a primary or key secondary endpoint.

Beyond oncology, goserelin-induced amenorrhea has been applied therapeutically in gynaecological conditions such as endometriosis and uterine fibroids, and even explored for managing severe uterine haemorrhage in patients with congenital aplastic anaemia. The mechanistic link between goserelin and amenorrhea is therefore direct, well-established, and clinically validated across multiple therapeutic contexts.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00427245	Phase 3	Completed	400	OPTION trial: Largest RCT evaluating goserelin for ovarian protection and prevention of early menopause in premenopausal breast cancer patients undergoing chemotherapy. Amenorrhea was a primary endpoint.
NCT00068601	Phase 3	Completed	257	SWOG S0230: LHRH analog (goserelin) administered during chemotherapy to reduce ovarian failure in hormone-receptor-negative breast cancer. Demonstrated ovarian protection benefit.
NCT02483767	Phase 3	Completed	98	Prospective RCT evaluating GnRH agonist goserelin for preservation of ovarian function during chemotherapy. Amenorrhea incidence was a key outcome measure.
NCT02132390	Phase 3	Unknown	300	Adjuvant toremifene ± goserelin in premenopausal HR+ breast cancer, with chemotherapy-induced amenorrhea as a stratification/outcome variable.
NCT03475758	Phase 2	Unknown	100	Goserelin for ovarian protection in premenopausal patients receiving cyclophosphamide-containing chemotherapy; menstruation outcome as primary endpoint.
NCT01218581	Phase 2/3	Completed	32	RCT comparing aromatase inhibitors vs. GnRH agonists for uterine adenomyosis management; amenorrhea as part of the treatment mechanism.
NCT00488722	N/A	Unknown	N/A	Single-arm study of Zoladex 3.6 mg combined with CEF chemotherapy as neo-adjuvant therapy; reversible amenorrhea induced by goserelin was a documented effect.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28472240	2017	Clinical Trial Report	Ann Oncol	OPTION trial results: GnRH agonist during chemotherapy reduced risk of premature ovarian insufficiency in early breast cancer patients.
12488406	2002	RCT	J Clin Oncol	ZEBRA study: Goserelin vs. CMF as adjuvant therapy; goserelin induced reversible amenorrhea with fewer toxic effects than chemotherapy.
14679153	2003	RCT	J Natl Cancer Inst	IBCSG Trial VIII: Chemotherapy followed by goserelin vs. each alone; demonstrated goserelin’s role in ovarian suppression and amenorrhea induction.
8513962	1993	RCT	Fertil Steril	Goserelin vs. low-dose OC for endometriosis-related pelvic pain; goserelin effectively induced amenorrhea as therapeutic mechanism.
25187267	2015	Clinical Outcome Study	Cancer Res Treat	Ovarian ablation with goserelin improved survival in premenopausal HR+ breast cancer patients without chemotherapy-induced amenorrhea.
17159194	2007	Comparative Study	J Clin Oncol	IBCSG Trial VIII QOL analysis: Compared amenorrhea rates, hot flashes, and quality of life across chemotherapy, goserelin, and combination arms.
1533675	1992	Review	J R Army Med Corps	Reviewed methods for therapeutic amenorrhea induction; goserelin described as “extremely effective” for this purpose.
12353820	2002	Review	Breast Cancer Res Treat	Overview of LHRH agonists in early breast cancer; goserelin induces reversible ovarian ablation with amenorrhea as the clinical marker.
10730389	1999	Clinical Study	Akush Ginekol	GnRH agonist (Zoladex) used to induce amenorrhea for treating severe uterine haemorrhage in adolescents with congenital aplastic anaemia; bleeding stopped within 2–4 days.
21325445	2011	Long-term Follow-up	Ann Oncol	IBCSG Trial VIII long-term results: Confirmed sustained efficacy of goserelin-based ovarian suppression in premenopausal node-negative breast cancer.

Philippines Market Information

Goserelin is currently not registered in the Philippines. There are no active marketing authorizations on record.

Authorization Number	Product Name	Dosage Form	Approved Indication
—	—	—	No registrations found

Note: Goserelin is marketed internationally under the brand name Zoladex (AstraZeneca) in subcutaneous depot implant formulations (3.6 mg and 10.8 mg). Philippines registration would be required before any clinical application.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Hormonal / Endocrine therapy (GnRH agonist) — not conventional cytotoxic
Myelosuppression Risk	Low (goserelin is not myelosuppressive; it acts via hormonal suppression)
Emetogenicity Classification	Minimal (not associated with significant nausea/vomiting)
Monitoring Items	Serum estradiol/testosterone levels, bone mineral density (long-term use), lipid profile, blood glucose, menopausal symptoms assessment
Handling Protection	Standard handling; does not require cytotoxic drug handling precautions

Safety Considerations

Please refer to the package insert for safety information. Detailed TFDA label warnings, contraindications, and drug interaction data are currently unavailable (data gap). International product labels (e.g., FDA, EMA) for Zoladex should be consulted.

Known class-effect considerations for GnRH agonists (from international labels):

Tumour flare: Initial transient increase in sex hormones may cause symptom flare in the first 1–2 weeks
Bone mineral density: Prolonged use associated with decreased BMD; duration of therapy should be considered
Cardiovascular risk: QT prolongation and increased cardiovascular risk have been reported with androgen deprivation therapy
Injection site reactions: Local reactions at subcutaneous depot injection site

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Goserelin’s ability to induce amenorrhea is a direct, well-characterised pharmacological effect with Level 1 evidence — at least 3 completed Phase 3 RCTs (OPTION, SWOG S0230, and NCT02483767) have demonstrated this effect. The TxGNN prediction (99.99%) aligns perfectly with established clinical evidence. This represents a validated drug-disease relationship rather than a speculative repurposing candidate.

To proceed, the following is needed:

Obtain Philippines FDA (PFDA) regulatory registration for goserelin (Zoladex)
Secure detailed safety data: package insert warnings, contraindications, and drug-drug interactions from the PFDA or reference regulatory agencies
Define the specific clinical context for amenorrhea induction (e.g., ovarian protection during chemotherapy, gynaecological conditions, or haematological indications)
Establish a safety monitoring plan including bone mineral density surveillance for prolonged use
Confirm route compatibility: subcutaneous depot implant availability and supply chain in the Philippines

Disclaimer: This report is for research reference only and does not constitute medical advice. Drug repurposing candidates require clinical validation before application.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.