Medroxyprogesterone Acetate
| Evidence Level: L3 | Predicted Indications: 6 |
Table of Contents
Medroxyprogesterone Acetate: Breast fibrocystic disease
One-Sentence Summary
Medroxyprogesterone acetate is a synthetic progestin (progesterone-like hormone) marketed in Canada in several single-ingredient products. The TxGNN model predicts it may be useful for breast fibrocystic disease, with a score of 0.9995. Support is limited: no registered clinical trials and 9 publications, mostly older, small or indirect studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Breast fibrocystic disease |
| TxGNN Prediction Score | 0.9995 |
| Evidence Level | L3 |
| Canada Market Status | Marketed (marketed DINs: 8 of 8) |
| Number of DINs | 8 (marketed: 8) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Medroxyprogesterone acetate is a progestin, a class that acts on progesterone receptors.
Fibrocystic breast changes are considered hormone-responsive. One review describes the underlying physiology as estrogen predominance with relative progesterone deficiency, which drives connective tissue and epithelial overgrowth. A progestin could, in principle, counter this estrogen-driven proliferation.
Two small, older clinical reports describe therapeutic use of medroxyprogesterone acetate in fibrocystic disease (one in adolescents, one in severe disease). However, studies of hormone replacement therapy show that combined estrogen-progestin regimens can increase mammographic breast density and epithelial proliferation. Safety signals for breast tissue are therefore mixed, and the evidence is dated and of low quality.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12841885 | 2003 | Clinical study | Climacteric | Compared five hormone replacement regimens in postmenopausal women with benign fibrocystic mastopathy |
| 2978834 | 1988 | Clinical study | Revista chilena de pediatria | Medroxyprogesterone acetate in adolescents with fibrocystic breast disease (no abstract available) |
| 6241963 | 1983 | Therapeutic trial | Revista chilena de obstetricia y ginecologia | Small therapeutic trial in severe fibrocystic breast disease (no abstract available) |
| 10576236 | 1999 | Clinical study | Int J Gynaecol Obstet | Mammographic and ultrasound changes, including new solid or cystic formations, during different HRT types |
| 11379380 | 2001 | Cohort/clinical study | Climacteric | Fine-needle cytology used to follow breast epithelial proliferation during HRT |
| 11379377 | 2001 | Clinical study | Climacteric | Effects of different HRT regimens on mammographic breast density |
| 3511705 | 1986 | Review | Am J Obstet Gynecol | Fibrocystic disease linked to estrogen predominance and progesterone deficiency; breast cancer risk raised two- to fourfold |
| 3657597 | 1987 | Review | Maturitas | Aetiology remains unclear; some progestogens, including this drug, caused myoepithelial hyperplasia in beagles, while oral contraceptives reduced incidence in women |
| 8603031 | 1996 | Preclinical/mechanistic | J Steroid Biochem Mol Biol | Androgen receptor-mediated growth control in breast and endometrial cancer cells (indirect) |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02267640 | AA-MEDROXY | Not available | Not available |
| 02244726 | AA-MEDROXY | Not available | Not available |
| 02277298 | AA-MEDROXY | Not available | Not available |
| 02221284 | TEVA-MEDROXYPROGESTERONE | Not available | Not available |
| 02523493 | DEPO-PROVERA | Not available | Not available |
All 8 single-ingredient licences are valid; the table lists the first five. Others include DEPO-PROVERA (02523493) and further TEVA-MEDROXYPROGESTERONE products.
Safety Considerations
- Breast tissue signals: Combined estrogen-progestin regimens have been associated with increased breast density and epithelial proliferation, and one review notes a two- to fourfold higher breast cancer risk in fibrocystic disease. This calls for caution.
- Drug Interactions: 100 interactions were found. The main ones listed are of moderate severity, mostly with glucose-lowering drugs (acarbose, metformin, canagliflozin, dapagliflozin, empagliflozin, glimepiride, chlorpropamide, saxagliptin, alogliptin), GLP-1 agonists (liraglutide, semaglutide, dulaglutide, albiglutide), insulins (aspart, degludec, detemir), and also dexamethasone, aprepitant, and clarithromycin.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The hormonal rationale is plausible, but the direct clinical evidence is only a few small, old, mostly uncontrolled reports. Breast safety signals with progestin exposure are mixed, and no registered trials exist.
To proceed, the following is needed:
- Obtain and review the Canadian package insert warnings and contraindications
- Mechanism of action data
- A modern controlled clinical study specific to fibrocystic breast disease, with breast safety endpoints
- Assessment of whether a suitable dose and route are available for this use
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.