Hydroxyprogesterone Caproate
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
- Hydroxyprogesterone Caproate
- Hydroxyprogesterone Caproate: From an Unspecified Original Indication to Endometrial Cancer
Hydroxyprogesterone Caproate: From an Unspecified Original Indication to Endometrial Cancer
One-Sentence Summary
Hydroxyprogesterone caproate is a long-acting injectable progestin marketed in Singapore as Proluton Depot, but the registered indication text is not available in the data compiled for this report. The TxGNN model predicts it may be effective for endometrial cancer, the most biologically coherent of its top predictions. Support consists of no registered clinical trials and 20 publications, mostly historical, uncontrolled or small clinical series from 1971 to 1995, plus one 2012 systematic review of progestins in general.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (the registered indication text is blank) |
| Predicted New Indication | Endometrial cancer (the top-ranked TxGNN prediction is endometriosis of uterus, which has only a case report as support) |
| TxGNN Prediction Score | 99.96% (endometriosis of uterus, the top-ranked prediction: 99.98%) |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold (a research question worth following up) |
Note on selection: I highlighted endometrial cancer rather than the rank-1 prediction because it is the only prediction with a meaningful body of literature. The other nine predictions are L4 or L5 and are summarised briefly at the end of the report.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on general pharmacology, hydroxyprogesterone caproate is a progestin. It binds progesterone receptors, opposes estrogen-driven proliferation and promotes differentiation in endometrial tissue.
Endometrial carcinoma is often hormone-sensitive, so this mechanism is a plausible fit. Progestin therapy for endometrial cancer and hyperplasia is already established with other agents (for example medroxyprogesterone acetate, megestrol and the levonorgestrel intrauterine system). The practical question is therefore whether this specific agent offers any advantage over current standards. The existing literature is largely historical and cannot answer that question.
The high TxGNN score is a computational prediction only. Several other top predictions, such as renal hypoplasia and infantile cerebral and cerebellar atrophy, have no plausible mechanism and are probably graph-based artifacts.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Of the 20 records linked to endometrial cancer, the most relevant are shown below. No randomized controlled trials were identified. Abstracts were frequently missing or truncated, so findings are summarised conservatively.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22245711 | 2012 | Systematic review | Gynecologic Oncology | Oncologic and reproductive outcomes of progestin therapy in endometrial hyperplasia and grade 1 adenocarcinoma (progestins in general, not this drug specifically) |
| 6985833 | 1980 | Prospective trial (non-randomized, historical comparison) | Cancer | Medroxyprogesterone acetate vs hydroxyprogesterone caproate in 114 women with metastatic endometrial adenocarcinoma; no significant difference in response or survival |
| 4011061 | 1985 | Clinical study | Obstetrics and Gynecology | Progestational agents including hydroxyprogesterone caproate gave an objective response in 11.2% of 155 patients with advanced or recurrent disease; response was higher in well-differentiated tumours |
| 3972284 | 1985 | Case series | Gynecologic Oncology | 19 young women with stage I endometrial carcinoma treated with hydroxyprogesterone caproate without surgery or radiation; clinical recovery confirmed in 15 |
| 3296435 | 1987 | Clinical study | Voprosy Onkologii | Adding hydroxyprogesterone caproate to radiation: 3-year survival 84.1% vs 74.8% in controls (non-randomized) |
| 4616884 | 1974 | Clinical series | Gynecologic Oncology | Treatment of advanced endometrial cancer with hydroxyprogesterone caproate |
| 5549492 | 1971 | Clinical series | Cancer | Hydroxyprogesterone caproate therapy in advanced endometrial cancer |
| 5573604 | 1971 | Clinical series | American Journal of Obstetrics and Gynecology | Progestogen treatment of recurrent endometrial carcinoma |
| 8565696 | 1995 | Comparative clinical study | Zhonghua Fu Chan Ke Za Zhi | Aminoglutethimide vs hydroxyprogesterone caproate vs combination: effects on serum and tissue hormone receptors and histology |
| 3885671 | 1985 | Clinical study | Acta Obstetricia et Gynecologica Scandinavica | Serum lipid effects in 57 stage I patients on adjuvant hydroxyprogesterone caproate (a safety-related finding, not efficacy) |
| 2932883 | 1985 | Pharmacokinetic study | Acta Obstetricia et Gynecologica Scandinavica | Intramuscular pharmacokinetics (peak serum levels 2-7 days after a 1000 mg dose) and effects on adrenal function |
Two further studies relate to the broader uterine cancer prediction: 6966107 (1980, immune effects in 34 patients) and 2815695 (1989, receptor effects with and without tamoxifen).
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14879P | PROLUTON DEPOT INJECTION 250MG/ML (Bayer AG) | Injection | Not available in the data compiled for this report |
Cytotoxicity
Hydroxyprogesterone caproate is a hormonal agent, not a conventional cytotoxic drug. Its use in endometrial cancer would be as hormonal therapy, so no cytotoxic handling requirements are expected. Please refer to the package insert warnings and precautions.
Safety Considerations
The package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for safety information.
The following comes from a knowledge graph (drug-disease contraindication links), not from label text, and should be confirmed against the official label. It flags these conditions:
- Cardiovascular and metabolic: hypertension, preeclampsia, diabetes mellitus, diabetic ketoacidosis, hyperglycemia, glucose intolerance, prediabetes
- Liver, kidney and gallbladder: liver disease, liver neoplasm, hepatocellular carcinoma, kidney disease, gallbladder disease
- Neurological and psychiatric: epilepsy, migraine, anxiety disorder, dysthymic disorder
- Other: asthma, female breast carcinoma
No drug interaction data were found.
Conclusion and Next Steps
Decision: Hold (the endometrial cancer question is worth pursuing as a research question)
Rationale: The mechanism is biologically sound and the literature on endometrial cancer is sizeable. However, it is almost entirely historical, uncontrolled or non-randomized, and there are no registered trials. The one direct comparison with medroxyprogesterone acetate showed no advantage. Established progestin options already exist, and the safety data needed for screening are missing.
To proceed, the following is needed:
- The HSA package insert (warnings, contraindications and registered indication), which is currently a blocking gap
- Mechanism of action data from DrugBank
- A structured review of the endometrial cancer literature, including full-text grading and a comparison with current standard progestin therapy
- Route and dose compatibility assessment for the injectable formulation in this setting
- Confirmation that the contraindicated conditions listed above are acceptable for the target population
Other Predictions (Summary)
| Predicted Indication | Evidence Level | Comment |
|---|---|---|
| Endometriosis of uterus (rank 1) | L5 | Only a case report of a pregnancy complication; no treatment evidence |
| Endometriosis of rectovaginal septum and vagina; cervix endometriosis; endometriosis in cutaneous scar | L5 | General progestin rationale only; no drug-specific data |
| Uterine corpus cancer | L4 | Three older non-randomized studies (1980-1989); overlaps with endometrial cancer |
| Breast fibrocystic disease | L5 | Prediction only |
| Renal hypoplasia (two entries); infantile cerebral and cerebellar atrophy | L5 | No plausible mechanism; likely graph artifacts |
All of these remain at Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.