Goserelin
| Evidence Level: L2 | Predicted Indications: 3 |
Table of Contents
- Goserelin
Goserelin: Amenorrhea (disease)
One-Sentence Summary
Goserelin is a gonadotropin-releasing hormone (GnRH) agonist, originally used to treat endometriosis. The TxGNN model predicts it may be effective for Amenorrhoea (as a deliberate, medically induced effect), with 1 clinical trial (indirect evidence only) and 15 publications currently supporting this direction. Amenorrhoea is an expected pharmacodynamic effect of goserelin, so this is better treated as a research question than a new therapeutic mechanism.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Amenorrhea (disease) |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L2 (as assigned in the data; the single Phase 3 trial is indirect and its status is unknown) |
| Australia Market Status | Listed on the PBS Schedule (2 of 2 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 2 (valid: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, goserelin is a GnRH agonist. Continuous administration desensitises pituitary GnRH receptors, suppressing LH and FSH release and lowering ovarian oestrogen production.
This produces a reversible, medically induced amenorrhoea (ovarian suppression). The same effect underlies its use in endometriosis, where lowering oestrogen reduces the activity of oestrogen-dependent ectopic tissue. It is also used in ovarian ablation for premenopausal breast cancer.
The prediction is therefore mechanistically coherent, but amenorrhoea here is a documented effect of treatment rather than a new disease target. Using it as a deliberate goal (for example, menstrual suppression, or ovarian protection during chemotherapy) is a separate clinical question that needs its own evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02132390 | Phase 3 | Unknown | 300 | Adjuvant toremifene with or without goserelin in premenopausal women with hormone receptor-positive breast cancer, with or without chemotherapy-induced amenorrhoea. The primary objective is oncologic outcome, so this is indirect evidence only. |
No ANZCTR identifiers were available in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12488406 | 2002 | RCT | J Clin Oncol | Goserelin versus CMF chemotherapy as adjuvant therapy in premenopausal node-positive breast cancer (ZEBRA study) |
| 14679153 | 2003 | RCT | J Natl Cancer Inst | Chemotherapy followed by goserelin versus either alone in node-negative premenopausal breast cancer (IBCSG Trial VIII) |
| 17159194 | 2007 | RCT (secondary analysis) | J Clin Oncol | Impact of chemotherapy, goserelin or both on amenorrhoea, hot flushes and quality of life |
| 8513962 | 1993 | RCT | Fertil Steril | Goserelin versus low-dose oral contraceptive for pelvic pain in endometriosis |
| 28472240 | 2017 | Meta-analysis/Review | Ann Oncol | OPTION trial: GnRH agonist for protection against chemotherapy-induced premature ovarian insufficiency |
| 25187267 | 2015 | Cohort | Cancer Res Treat | Goserelin ovarian ablation improved survival in stage II/III hormone receptor-positive breast cancer without chemotherapy-induced amenorrhoea |
| 21325445 | 2011 | Long-term follow-up | Ann Oncol | Long-term results of IBCSG Trial VIII (endocrine, chemotherapy and combined therapy) |
| 1533675 | 1992 | Review | J R Army Med Corps | Therapeutic induction of amenorrhoea, including goserelin, in female military personnel |
| 12353820 | 2002 | Review | Breast Cancer Res Treat | LHRH agonists in early breast cancer and the benefits of reversible ovarian ablation |
| 12734855 | 2003 | Review | Br J Surg | Methods and relevance of ovarian ablation in adjuvant treatment of breast cancer |
Most of this literature concerns breast cancer, where amenorrhoea is a side effect or surrogate marker rather than the treatment target.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 1454M | Zoladex Implant | Subcutaneous implant 3.6 mg (as acetate) in pre-filled injection syringe | Not stated in the compiled data |
| ARTG 9064C | ZolaCos CP 3.6/50 | Pack with 1 goserelin 3.6 mg subcutaneous implant and 28 bicalutamide 50 mg tablets | Not stated in the compiled data |
Safety Considerations
- Contraindication-related conditions (not label text): hypertensive disorder, hypertension, hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, hypercalcaemia, nephrocalcinosis, phosphorus metabolism disease, obesity disorder, monogenic obesity, urinary tract obstruction.
- Drug interactions: 100 interactions were identified. Those listed here are examples from the 20 interactions shown.
- Major: dolasetron.
- Moderate: antidiabetic agents (acarbose, albiglutide, alogliptin, canagliflozin, chlorpropamide, dapagliflozin, dulaglutide, empagliflozin, glimepiride, linagliptin, metformin, saxagliptin), clarithromycin, famotidine, loperamide, palonosetron, and bowel preparations or laxatives (bisacodyl, picosulfuric acid, polyethylene glycol).
- The prominence of antidiabetic agents is consistent with the glucose-tolerance concerns noted above.
Label warnings and contraindications were not available in the compiled data. Please refer to the TGA-approved Product Information (PI) for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Amenorrhoea is an expected pharmacological effect of goserelin, not a distinct disease indication. The only trial is an indirect, status-unknown breast cancer study, and the literature mostly addresses oncology contexts. The high TxGNN score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence for a new therapeutic use.
To proceed, the following is needed:
- A clear definition of the intended use (for example, menstrual suppression or ovarian protection during chemotherapy) and the target population
- Direct clinical evidence for that use, such as randomised trials with amenorrhoea or ovarian function as the primary endpoint
- Approved indication text and PI safety information (warnings, contraindications) for the Australian products
- Mechanism of action data to complete the mechanistic analysis
- Review of the interaction profile, particularly with antidiabetic agents and QT-prolonging drugs, and of bone density and hypo-oestrogenic effects with longer-term use
Other Predicted Indications (for reference)
- Cervix endometriosis, endometriosis of the rectovaginal septum and vagina: anatomical subtypes of the approved indication (L4). The mechanistic rationale is sound, but no site-specific trials or literature were retrieved. These are research questions.
- Endometriosis in cutaneous scar: a single case report (PMID 19753740) describes combined medical and surgical treatment (L4). Surgical excision remains the primary treatment.
- The recommendation for these is Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.