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 that is already marketed in India as oral tablets and an injectable. The TxGNN model predicts it may be useful for breast fibrocystic disease, with a score of 0.9995. Support is limited: there are no registered clinical trials and 9 publications, including two small, older, uncontrolled clinical reports. Evidence is rated L3.
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 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for MPA is not available in the data compiled for this report. Based on general pharmacology, MPA acts as a progestin, an agonist at the progesterone receptor.
The literature describes fibrocystic breast disease as driven by estrogen predominance and relative progesterone deficiency. This leads to overgrowth of connective tissue and then of the epithelium. A progestin could therefore plausibly counter estrogen-driven proliferation of breast tissue.
The evidence is mixed. Two small, older clinical reports suggest a possible benefit: a 1983 therapeutic trial in severe disease and a 1988 series in adolescents. However, hormone replacement therapy (HRT) studies of estrogen combined with MPA report increased breast density and epithelial proliferation. This raises a safety concern and conflicts with the idea of benefit. No modern controlled trials exist.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6241963 | 1983 | Clinical trial (small, uncontrolled) | Rev Chil Obstet Ginecol | Therapeutic trial of MPA in severe fibrocystic breast disease (no abstract available) |
| 2978834 | 1988 | Case series | Rev Chil Pediatr | MPA used in fibrocystic breast disease in adolescents (no abstract available) |
| 3511705 | 1986 | Review | Am J Obstet Gynecol | Fibrocystic disease results from estrogen predominance and progesterone deficiency; breast cancer risk is increased two- to fourfold |
| 3657597 | 1987 | Review | Maturitas | Oral contraceptives (estrogen plus progestogen) reduce fibrocystic breast disease incidence; some progestogens, including MPA, caused myoepithelial hyperplasia in beagles |
| 12841885 | 2003 | Cohort | Climacteric | Compared five HRT regimens in postmenopausal women with benign fibrocystic mastopathy |
| 10576236 | 1999 | Cohort | Int J Gynaecol Obstet | Mammographic and ultrasound changes in breast tissue during different types of HRT |
| 11379380 | 2001 | Cohort | Climacteric | Breast epithelial proliferation during HRT assessed by fine-needle cytology |
| 11379377 | 2001 | Cohort | Climacteric | Mammographic breast density across HRT regimens (continuous combined, unopposed transdermal, low-potency estrogen) |
India Market Information
MPA is marketed in India, and all 20 licences found in the local data are valid. The list below may be partial, and approved indication text is not recorded in the local data.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 87837 | Farlutal 5mg Tablet (Pfizer Ltd) | Strip of 10 tablets | Not available |
| 182098 | Parlutal 2.5mg Tablet (Pfizer Ltd) | Strip of 10 tablets | Not available |
| 80190 | Empeea 2.5mg Tablet (Pfizer Ltd) | Strip of 10 tablets | Not available |
| 134176 | Meprate 5mg Tablet (Serum Institute Of India Ltd) | Strip of 10 tablets | Not available |
| 174374 | Pari Contraceptive Injection (Janani) | Box of 1 injection | Not available |
Safety Considerations
- Hormone therapy context: Studies of estrogen combined with MPA report increased mammographic breast density and epithelial proliferation. This is a particular concern when the target condition is a proliferative breast disease.
- Drug interactions: 205 interactions are recorded, and the 20 listed are all of moderate level. They mainly involve glucose-lowering agents: acarbose, metformin, glimepiride, chlorpropamide, the gliptins (alogliptin, saxagliptin), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), GLP-1 agonists (liraglutide, semaglutide, dulaglutide, albiglutide) and insulins (aspart, degludec, detemir). Other interacting drugs include dexamethasone, aprepitant, clarithromycin and pegvaliase.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The biological rationale is plausible, and two small, older, uncontrolled clinical reports exist (evidence level L3). However, there are no randomized trials, and HRT data suggest that MPA combined with estrogen may increase breast proliferation. This should be treated as a research question rather than a candidate ready for development.
To proceed, the following is needed:
- A controlled clinical study of MPA alone (without estrogen) in fibrocystic breast disease, with breast density and proliferation outcomes
- A focused safety review of breast effects of MPA, including the proliferation signals seen in HRT studies
- Mechanism-of-action data for MPA in breast tissue
- Package insert warnings and contraindications for the marketed Indian products
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.