Medroxyprogesterone Acetate
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Medroxyprogesterone Acetate: From Endometriosis to Amenorrhea
One-Sentence Summary
Medroxyprogesterone acetate is a synthetic progestin, originally used for endometriosis, endometrial cancer, postmenopausal osteoporosis and postmenopausal atrophic vaginitis. The TxGNN model predicts it may be effective for amenorrhea, but no clinical trials are registered and the 20 publications retrieved are mostly contraception reviews, so the evidence is indirect.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Endometriosis, endometrial cancer, postmenopausal osteoporosis, postmenopausal atrophic vaginitis (the Singapore licence records contain no indication text) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.999% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Medroxyprogesterone acetate is a synthetic progestin. Detailed mechanism of action data is not currently available. Based on known information, it belongs to the progestin class, its efficacy in endometriosis and endometrial conditions is established, and mechanistically it may be applicable to amenorrhea.
In secondary amenorrhea with adequate endogenous estrogen, a progestin withdrawal challenge induces endometrial shedding, so a plausible pharmacological rationale exists. The existing indications also involve progestin action on the endometrium, which supports the link.
However, the retrieved literature is dominated by contraception and Depo-Provera reviews. In those papers amenorrhea is an adverse effect or expected outcome, not a treatment target. Direct evidence for amenorrhea as a treatment indication is therefore lacking.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The retrieved publications are mainly reviews on contraception. The most relevant are listed below (abstracts were unavailable for several).
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23641480 | 2013 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Combination injectable contraceptives are highly effective, but bleeding pattern changes may limit acceptability |
| 18843662 | 2008 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Earlier version of the same review on combination injectable contraceptives |
| 8178904 | 1994 | Review | Am J Obstet Gynecol | DMPA 150 mg every 3 months has contraceptive efficacy above 99%; used by 30 million women in over 90 countries |
| 8725701 | 1996 | Review | J Reprod Med | Counselling and side-effect management for DMPA users |
| 8829701 | 1996 | Review | Int J Fertil Menopausal Stud | Long-acting contraceptive options, with pregnancy rates below 1 per 100 woman-years |
| 6119259 | 1981 | Review | Int J Gynaecol Obstet | Postpartum contraception; ovulation return is unpredictable regardless of postpartum amenorrhea |
| 6141923 | 1984 | Review | Drug Intell Clin Pharm | Drug-induced infertility through effects on the hypothalamic-pituitary-gonadal axis |
| 8492647 | 1993 | Review | MCN Am J Matern Child Nurs | Depo-Provera overview |
| 1604074 | 1992 | Review | Rev Med Liege | Hormonal contraception overview |
| 120837 | 1979 | Review | IARC Monogr | Carcinogenic risk evaluation of medroxyprogesterone acetate |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN04540P | Depo-Provera Sterile Aqueous Suspension 50 mg/ml | Injection | Not recorded |
| SIN03841P | Provera Tablet 10 mg | Tablet | Not recorded |
| SIN10513P | Provera Tablet 5 mg | Tablet | Not recorded |
Safety Considerations
- Contraindications suggested by the knowledge graph (not taken from label text; they need verification against the package insert): hypertension, liver disease and liver failure, kidney disease, gallbladder disease, epilepsy, diabetes mellitus and diabetic ketoacidosis, asthma, systemic lupus erythematosus, hypothyroidism, osteoporosis, hypercalcemia, hypertriglyceridemia, anxiety and related mood disorders, substance abuse/dependence, and female breast carcinoma.
- Drug Interactions: 100 interactions were found. The 20 reviewed are all rated Moderate. They are mainly glucose-lowering drugs (metformin, acarbose, glimepiride, chlorpropamide, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists, insulins). Others include dexamethasone, aprepitant, clarithromycin and pegvaliase.
- Progestins are not indicated in pregnancy.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but there are no registered trials and no direct clinical evidence for amenorrhea as a treatment target. The literature is mostly contraception reviews, where amenorrhea is a side effect. Safety data from the package insert are missing, and the knowledge graph flags many contraindicated conditions.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (required for safety screening)
- Detailed mechanism of action data
- Targeted literature search for clinical studies of progestin treatment in primary or secondary amenorrhea
- Confirmation of the approved indications for each Singapore licence
- Comparison with established progestin withdrawal protocols and a benefit-risk review for patients with the flagged comorbidities
Other Predicted Indications (for reference)
| Rank | Predicted Indication | Evidence Level | Note | |------|------|------|------| | 2 | Breast fibrocystic disease | L3 | Small, dated clinical reports (1983, 1988); HRT studies suggest progestin combinations may increase breast density, so benefit-risk is uncertain | | 3 | Benign mammary dysplasia | L4 | Same disease spectrum as above; no direct evidence | | 4 | Cervix endometriosis | L4 | Plausible extension of the endometriosis indication; retrieved literature is off-target | | 5 | Endometriosis of rectovaginal septum and vagina | L5 | Model inference only; often needs surgery | | 6 | Endometriosis in cutaneous scar | L5 | Model inference only; typically managed surgically | | 7-8 | Renal hypoplasia (bilateral / unspecified) | L5 | No plausible mechanism; likely a knowledge-graph artifact | | 9-10 | Blunt duct adenosis / apocrine adenosis of breast | L5 | Fibrocystic-spectrum lesions; no direct evidence |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.