Cyproterone Acetate

Evidence Level: L4

Predicted Indications: 9

Cyproterone Acetate

Pharmacist Assessment Report

Cyproterone Acetate: From Androgen-Dependent Conditions to Migraine Disorder

One-Sentence Summary

Cyproterone acetate (CPA) is a progestogen with antiandrogen activity. It is marketed in Canada as a single-ingredient product and in combination with ethinyl estradiol, and it is used for androgen-dependent conditions such as acne, hirsutism and prostate cancer. The TxGNN model predicts it may be effective for migraine disorder, but there are no registered clinical trials and only 3 indirect publications. The evidence is weak, and the literature suggests caution because hormonal exposure can trigger or worsen migraine.

Quick Overview

Item	Content
Original Indication	Not stated in the Canadian licence data. Pharmacology data lists androgen-dependent conditions (prostate cancer, acne, hirsutism) and hormonal uses (menopausal hot flushes, combined oral contraceptives).
Predicted New Indication	Migraine disorder
TxGNN Prediction Score	0.9966
Evidence Level	L4 (no trials; indirect mechanistic literature only)
Canada Market Status	Marketed (marketed DINs: 9 of 9)
Number of DINs	9 (marketed: 9)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available. Based on known information, cyproterone acetate is a synthetic progestogen that blocks the androgen receptor (AR). Its efficacy in androgen-dependent conditions and in combined contraceptive use is established, and it may mechanistically be applicable to migraine through hormonal effects on the brain.

Migraine is sensitive to fluctuations in sex hormones. A 2003 review reports that progestins interact with the GABA-A receptor and with dopamine and opioid systems. It also notes that CPA increases dopaminergic responses and binds opiate receptors independently of its classical antiandrogen effect. This gives a plausible but indirect biological link.

None of the retrieved literature shows CPA treating migraine. Hormone exposure can also trigger or worsen migraine, so the direction of effect is uncertain. The high model score may partly reflect shared hormonal and vascular associations rather than therapeutic benefit.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
14670648	2003	Review	Maturitas	Progestins interact with GABA-A receptors and dopamine and opioid systems; CPA increases dopaminergic responses and binds opiate receptors.
12390622	2002	Cohort	Headache	Compared three oral hormone replacement regimens and their effects on migraine in postmenopausal women; regimens affected migraine differently.
10857213	2000	Review	Zentralblatt fur Gynakologie	Long-term side effects of CPA-containing gynecological therapy, including discussion of mutagenic potential. Not about migraine.

None of these papers shows CPA treating migraine.

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02390760	MED-CYPROTERONE	Not available	Not available
02395797	RIVA-CYPROTERONE	Not available	Not available
02245898	CYPROTERONE	Not available	Not available
00704431	ANDROCUR	Not available	Not available
02233542	DIANE-35	Not available	Not available

Nine licences are valid in total. The remaining four are TEVA-CYPROTERONE / ETHINYL ESTRADIOL (02309556), CYESTRA-35 (02290308), CLÉO-35 (02436736) and TARO-CYPROTERONE/ETHINYL ESTRADIOL (02425017).

Safety Considerations

Drug Interactions: The only interaction record is pharmacological. CPA acts on the androgen receptor (AR), which is its known target and not a drug-drug interaction.
Related safety signals from the migraine literature: Reviews of hormonal contraception describe increased venous thromboembolism and arterial ischemic risk with combined hormonal contraceptives. Migraine with aura is a recognized contraindication for combined hormonal contraceptives. CPA-containing products have been associated with higher thrombotic risk.

For labelled warnings and contraindications, please refer to the package insert.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction rests on a model score and indirect literature. No trial or paper shows CPA benefiting migraine, and the thrombotic and hormonal risks are a particular concern in migraine, especially migraine with aura.

To proceed, the following is needed:

Mechanism of action data from DrugBank
Package insert warnings and contraindications from Health Canada, to complete safety screening
Direct clinical or preclinical evidence of CPA effect on migraine, including whether the effect is beneficial or harmful
A vascular and thromboembolic risk assessment in migraine populations, especially migraine with aura

Other Predicted Indications (for reference)

Predicted Indication	Evidence Level	Note	Decision
Amenorrhea	L3	One Phase 4 trial of ethinyl estradiol/CPA in hyperandrogenic irregular cycles (NCT01103518, status unknown); evidence is not specific to amenorrhea	Research Question
Breast fibrocystic disease	L4	Indirect and dated literature	Hold
Thrombophilia	L5	The literature shows CPA-containing contraceptives raise thrombotic risk, a harm signal	Hold
Migraine with brainstem aura, migraine susceptibility	L5	Literature is about vascular risk, a safety signal	Hold
Prinzmetal angina, antithrombin deficiency type 2, heparin cofactor 2 deficiency, factor 5 excess with spontaneous thrombosis	L5	Prediction only, with no clinical evidence; several are thrombosis-related, where CPA is a risk factor	Hold

Disclaimer

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