Dienogest
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Dienogest: From Endometriosis-Type Progestin Therapy to Amenorrhea
One-Sentence Summary
Dienogest is an oral progestin that is marketed in Singapore as 2 mg tablets (its approved indication text is not available in the data compiled for this report). The TxGNN model predicts it may be associated with amenorrhea, but there are no registered clinical trials and only 7 publications retrieved, most of which are indirect. Amenorrhea is better understood as a known effect of dienogest than as a treatment target.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the licence data (the literature describes dienogest as used for endometriosis) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.71% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on the literature, dienogest is a fourth-generation progestin with selective progesterone-receptor activity and minimal androgenic activity. It has an antiproliferative effect on the endometrium and partly suppresses ovarian oestradiol production.
Amenorrhea is a frequent, well-documented outcome of dienogest treatment in endometriosis, where inducing amenorrhoea and a hypoestrogenic environment is a treatment aim. This is the likely source of the model's prediction. However, the link is mainly a pharmacodynamic effect or adverse effect, not evidence that dienogest treats amenorrhea. Progestins as a class are used in secondary amenorrhea (withdrawal bleeding, endometrial protection), which gives plausible but indirect support. No direct data for dienogest in treating amenorrhea were found.
Other predicted indications (ranks 2–10) are weaker. Primary ovarian failure and hypogonadotropic hypogonadism are mechanistically opposed to dienogest's ovary-suppressing action. Breast fibrocystic disease has one small, low-level study. The remainder (such as growth hormone deficiency and chromosomal disorders) appear to be model artefacts with no supporting evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39090694 | 2024 | Systematic review / Bayesian meta-analysis | BMC Pharmacol Toxicol | Summarises adverse events of dienogest and their prevalence in endometriosis and adenomyosis |
| 29161960 | 2018 | Retrospective cohort (514 women) | Reprod Sci | Long-term (>12 months) dienogest 2 mg daily in ovarian endometrioma: efficacy, safety and recurrence |
| 34405378 | 2022 | Review | Rev Endocr Metab Disord | Endocrine background of hormonal treatments for endometriosis |
| 41329046 | 2026 | Clinical/pharmacodynamic study | Eur J Contracept Reprod Health Care | Further evidence for 2 mg dienogest in endometriosis; notes amenorrhoea induction as a treatment objective |
| 42438810 | 2026 | Case report | JCEM Case Reports | Primary hyperparathyroidism unmasked after dienogest-altered oestrogen dynamics |
| 40543564 | 2025 | Review | J Pediatr Adolesc Gynecol | Advanced visualisation for Müllerian anomalies (not directly about dienogest) |
| 34918698 | 2021 | Case report | Medicine | Ovarian granulosa cell tumour in a patient with PCOS (not relevant to dienogest therapy) |
None of these studies tests dienogest as a treatment for amenorrhea. For the rank-3 prediction (breast fibrocystic disease), one small 2009 pilot study (19499407) in 21 women with endometriosis, given high-dose dienogest, reported reduced mammary gland size and regression of mastopathic changes.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15891P | DIENOSIS TABLETS 2 MG | Tablet | Not available |
| SIN16681P | VIENOMET TABLETS 2MG | Tablet | Not available |
| SIN16682P | DIMETRUM TABLET 2MG | Tablet | Not available |
| SIN16854P | DIENOMET TABLET 2MG | Tablet | Not available |
All four registrations are valid single-ingredient oral tablets.
Safety Considerations
- Contraindications suggested by the knowledge graph (these are model-derived associations, not label text): hypertension, epilepsy, anxiety and neurotic disorders, porphyria, kidney disease, liver disease, gallbladder disease, hypothyroidism, systemic lupus erythematosus, asthma, diabetes mellitus and diabetic ketoacidosis, hypertriglyceridemia, hypercalcemia and related calcium/phosphorus disorders, female breast carcinoma, and thrombophlebitis.
- Drug Interactions: 37 interactions were identified in total. Major-level interactions among those listed include sugammadex, griseofulvin, bexarotene, brigatinib, dabrafenib and encorafenib. Moderate-level interactions include linaclotide, metreleptin, prucalopride, miltefosine, adalimumab, anakinra, cladribine and others. Ethanol is a minor interaction.
- Literature signal: a 2026 case report describes primary hyperparathyroidism unmasked after starting dienogest, which is consistent with the calcium-related knowledge-graph flags.
Please refer to the package insert for label warnings and contraindications, which were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but there are no clinical trials and no literature testing dienogest as a treatment for amenorrhea. Amenorrhea is mainly an expected effect of dienogest, so the prediction is mechanistically circular rather than a true new therapeutic use. Evidence is limited to L4, and the safety label data needed for screening were not available.
To proceed, the following is needed:
- Singapore package insert (HSA) warnings, contraindications and approved indication text
- Detailed mechanism of action data
- Direct clinical evidence of dienogest treating (not causing) amenorrhea, or clarification of the intended use
- A safety review of the knowledge-graph contraindications, especially cardiovascular, hepatic and calcium-metabolism concerns
- Reassessment of other predicted indications, of which breast fibrocystic disease has the only (weak) supporting signal
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.