Cyproterone Acetate
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Cyproterone Acetate: From Androgen-Dependent Conditions to Migraine Disorder
One-Sentence Summary
Cyproterone acetate is a synthetic progestin with antiandrogen activity. It is used for androgen-dependent conditions (such as prostate cancer, acne, and hirsutism) and as a component of combined oral contraceptives. The TxGNN model predicts it may be effective for migraine disorder, but no clinical trials and only 3 publications (reviews and a cohort study, none showing that the drug treats migraine) are available. This prediction is computational only and is not supported by direct evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence records. Published pharmacology describes androgen-dependent diseases (prostate cancer, benign prostatic hyperplasia), acne and hirsutism in women, menopausal hot flushes, and use in combined oral contraceptives |
| Predicted New Indication | Migraine disorder |
| TxGNN Prediction Score | 99.66% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Pharmacology data show that cyproterone acetate binds the androgen receptor. It is also a progestin with antiandrogen activity, and it is used as a form of chemical castration and in contraceptive pills.
The link to migraine is indirect and hormonal. Migraine is modulated by hormonal changes such as estrogen withdrawal, and progestins can affect central nervous system excitability. A 2003 review notes that progestins interact with GABA-A receptors and with dopamine and opioid systems, and that cyproterone acetate increases dopaminergic responses and binds opiate receptors independently of its classical effects. This makes a link plausible in theory.
However, none of the retrieved papers shows that cyproterone acetate treats migraine. The hormone-therapy literature suggests hormonal agents can aggravate or alter migraine. The high TxGNN score reflects a knowledge-graph prediction, not clinical proof.
Other predictions for this drug point to a safety signal rather than a therapeutic one. Several (migraine with brainstem aura, thrombophilia, antithrombin deficiency, factor V excess) most likely reflect the known thrombosis risk of cyproterone acetate-containing combined contraceptives.
Clinical Trial Evidence
Currently no related clinical trials registered for migraine disorder.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14670648 | 2003 | Review | Maturitas | Progestins interact with GABA-A, dopamine, and opioid systems. Cyproterone acetate increases dopaminergic responses and binds opiate receptors |
| 12390622 | 2002 | Cohort | Headache | Three oral hormone replacement regimens had differing effects on migraine course in postmenopausal women. This is not specific to cyproterone acetate |
| 10857213 | 2000 | Review | Zentralblatt fur Gynakologie | Long-term side effects of cyproterone acetate-containing gynaecological therapy, including a discussion of mutagenic potential. Not about migraine |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13545P | PROCUR TABLETS 50MG | Tablet | Not stated in licence record |
| SIN04784P | DIANE-35 TABLET | Tablet, sugar coated | Not stated in licence record |
| SIN12117P | ESTELLE-35 TABLET | Tablet, film coated | Not stated in licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Hormonal antiandrogen (not a conventional cytotoxic agent). It is used in prostate cancer |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The only interaction entry is a pharmacological target relationship (androgen receptor), not a drug-drug interaction with a graded severity level.
- Thrombosis risk (from the literature): Multiple cohort and case-control studies and guidelines associate cyproterone acetate-containing combined oral contraceptives with higher venous thromboembolism risk, prothrombotic changes such as activated protein C resistance, and greater risk with factor V Leiden. Reviews also note that migraine with aura is a risk factor for ischaemic stroke with combined hormonal contraceptives, which is relevant for any use in migraine patients.
- Long-term safety: A review discusses a possible mutagenic potential of the drug, although a large multicentre study did not find an increase in the events examined.
Please refer to the package insert for further safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a computational score alone. There are no clinical trials, and the literature gives no evidence of benefit in migraine. The hormone-therapy and thrombosis literature points toward caution, especially in patients with aura.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which are currently missing and block safety screening
- Detailed mechanism of action data
- Original approved indication text for the three Singapore licences
- Evidence of efficacy in migraine from controlled studies, and a benefit-risk assessment addressing thromboembolic and stroke risk
- Route compatibility assessment (not yet completed)
Note on other predictions: Amenorrhea (L3) is the only other prediction with a clinical trial: NCT01103518, a Phase 4 trial of ethinyl estradiol and cyproterone acetate preparations in irregular menstruation of hyperandrogenic origin (n=100, status unknown, no results). It is better supported mechanistically and is worth pursuing as a research question. Thrombophilia and related coagulation predictions should be treated as safety signals and excluded from repurposing consideration.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.