Medroxyprogesterone Acetate
| Evidence Level: L3 | Predicted Indications: 6 |
Table of Contents
Medroxyprogesterone Acetate: Breast fibrocystic disease
One-Sentence Summary
Medroxyprogesterone acetate (MPA) is a synthetic progestin with an oral tablet currently marketed in Australia. The TxGNN model predicts it may be useful for breast fibrocystic disease. Support is limited to no registered clinical trials and 9 publications, which are mostly dated, small or indirect, and include breast safety signals.
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 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. MPA is a progestin, a class that acts on progesterone receptors and opposes estrogen-driven tissue growth.
The literature describes fibrocystic breast disease as reflecting relative estrogen predominance and progesterone deficiency, with hyperproliferation of breast connective tissue and epithelium. A progestin could plausibly counter this, and that was the rationale for two older MPA treatment series, in severe disease (1983) and in adolescents (1988).
The evidence is conflicting. Studies of hormone replacement regimens that include a progestin suggest that combined estrogen-progestin therapy can increase breast epithelial proliferation and mammographic density. Animal data also show that MPA can cause proliferative breast changes in dogs. The older MPA studies are small and of uncertain design, and the full text of their results was not available. The prediction is therefore biologically conceivable but unproven, and it carries a breast safety concern.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6241963 | 1983 | Clinical trial (small, non-registered) | Rev Chil Obstet Ginecol | Therapeutic trial of MPA in severe fibrocystic breast disease. No abstract available. |
| 2978834 | 1988 | Clinical study (adolescents) | Rev Chil Pediatr | MPA used in adolescents with fibrocystic breast disease. No abstract available. |
| 12841885 | 2003 | Clinical study | Climacteric | Compared five hormone replacement regimens in postmenopausal women with benign fibrocystic mastopathy. |
| 11379380 | 2001 | Cohort/clinical study | Climacteric | Used fine-needle-aspiration cytology to follow breast epithelial proliferation during hormone replacement therapy. |
| 11379377 | 2001 | Clinical study | Climacteric | Assessed the effect of different hormone replacement regimens on mammographic breast density. |
| 10576236 | 1999 | Clinical study (imaging) | Int J Gynaecol Obstet | Mammographic and ultrasound changes, including new solid or cystic lesions, during hormone replacement therapy. |
| 3511705 | 1986 | Review | Am J Obstet Gynecol | Fibrocystic disease is linked to estrogen predominance and progesterone deficiency. Breast cancer risk is increased two- to fourfold in these patients. |
| 3657597 | 1987 | Review | Maturitas | Aetiology remains unclear. Oral contraceptives reduce incidence, but MPA induced myoepithelial hyperplasia in beagles. |
| 8603031 | 1996 | Preclinical/mechanistic | J Steroid Biochem Mol Biol | Androgen receptor-mediated growth control in breast and endometrial cells. Indirect relevance. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 13849X | Ralovera | Tablet containing medroxyprogesterone acetate 10 mg (oral) | Not stated in the data compiled for this report |
The approved indication text for this entry is not recorded in the local data. The market status is Marketed, and the single licence is valid.
Safety Considerations
Label-based warnings and contraindications are not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for authoritative safety information.
- Conditions flagged for caution: The compiled data flag several conditions as potential contraindications or cautions. These come from a disease-level relationship source, not from label text, and should be checked against the PI. They include hypertension, liver disease and liver failure, kidney disease, gallbladder disease, epilepsy, asthma, diabetes mellitus, hypothyroidism, systemic lupus erythematosus, hypercalcaemia-related conditions, osteoporosis, hypertriglyceridaemia, substance abuse/dependence, anxiety and mood disorders, and female breast carcinoma.
- Drug interactions: The compiled data list 100 interactions, and all of those shown are of Moderate severity. They are mainly with glucose-lowering agents, including acarbose, metformin, glimepiride, chlorpropamide, insulins, and the DPP-4, SGLT2 and GLP-1 classes. Others are dexamethasone, aprepitant and clarithromycin. Monitor glycaemic control when co-prescribing.
- Breast-specific concern: The hormone replacement literature and animal data above suggest progestins may increase breast epithelial proliferation and mammographic density. This is directly relevant to a breast indication.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic rationale is plausible, and two small, dated MPA studies address this disease directly. However, there are no registered trials, no controlled evidence, and conflicting breast safety signals. This is a research question rather than a candidate ready for development.
To proceed, the following is needed:
- Full-text review of the 1983 and 1988 MPA studies to assess design, outcomes and safety.
- Mechanism of action data for MPA in breast tissue.
- A structured benefit-risk assessment of breast proliferation and density effects.
- Review of the TGA Product Information for warnings and contraindications.
- A controlled study design, if pursued, with breast imaging and safety endpoints.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.