Dienogest

證據等級: L5

預測適應症: 10 個

Dienogest: From Endometriosis to Amenorrhea

One-Sentence Summary

Dienogest is a fourth-generation progestin primarily used for the treatment of endometriosis and endometriosis-related pelvic pain. The TxGNN model predicts it may be effective for Amenorrhea, with 0 clinical trials and 6 publications indirectly related to this direction. However, expert review flags this prediction as a likely false positive — amenorrhea is a well-known pharmacological side effect of dienogest (incidence ~20–30%), not a therapeutic target.

Quick Overview

Item	Content
Original Indication	Endometriosis (derived from literature; license-level indication text unavailable)
Predicted New Indication	Amenorrhea (disease)
TxGNN Prediction Score	99.71%
Evidence Level	L4 (mechanism/pharmacological studies only)
Malaysia Market Status	✓ Marketed
Number of Registrations	6
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this evidence pack. Based on known pharmacology, dienogest is a selective progestin with high affinity for the progesterone receptor and minimal androgenic activity. It suppresses the hypothalamic-pituitary-ovarian (HPO) axis, inhibits ovulation, and creates a hypoestrogenic environment that causes endometrial atrophy — the basis for its efficacy in endometriosis.

This prediction is flagged as a likely false positive. Amenorrhea (absence of menstruation) is a direct and expected pharmacological consequence of dienogest’s HPO axis suppression. In the clinical management of endometriosis, the induction of amenorrhea is actually considered a marker of therapeutic efficacy, not a disease to be treated. The TxGNN knowledge graph has detected a strong “drug–amenorrhea” association, but this reflects a drug–side effect relationship, not a drug–therapeutic indication relationship.

Among the remaining 9 predicted indications, several share a similar pattern of false association: primary ovarian failure (rank 2) and hypogonadotropic hypogonadism (rank 7) are pharmacologically contraindicated, while chromosomal anomalies (ranks 8–10) and genetic syndromes (ranks 5–6) have no mechanistic basis. Only breast fibrocystic disease (rank 3) has limited theoretical plausibility based on progesterone’s anti-estrogenic effects on breast tissue, though evidence is minimal (1 pilot study).

Clinical Trial Evidence

Currently no related clinical trials registered for dienogest in amenorrhea.

Note: One clinical trial (NCT04306276) was retrieved under the related prediction for primary ovarian failure (rank 2), but its actual focus is dienogest pretreatment before IVF in endometriosis patients — not relevant to amenorrhea as a therapeutic target.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
39090694	2024	Systematic Review	BMC Pharmacol Toxicol	Systematic review of adverse effects of dienogest; amenorrhea identified as a common side effect during endometriosis treatment
41329046	2026	Pharmacological Study	Eur J Contracept Reprod Health Care	High inhibition ratio of dienogest 2 mg supports its use in endometriosis by inducing amenorrhea and a hypoestrogenic environment
34405378	2022	Review	Rev Endocr Metab Disord	Hormonal treatments for endometriosis; dienogest reduces ectopic endometrial implants via estrogen suppression
29161960	2018	Cohort	Reprod Sci	Long-term dienogest use (>12 months) in ovarian endometrioma; efficacy and safety assessed in 514 women across 7 centres
19499407	2009	Pilot Study	Gynecol Endocrinol	High-dose dienogest (2×10 mg) for 24 weeks caused mammary gland size reduction and regression of mastopathic changes in 21 endometriosis patients
40543564	2025	Case/Imaging	J Pediatr Adolesc Gynecol	Advanced visualization for Müllerian anomalies; dienogest mentioned as medical management — tangentially related

Note: These publications discuss amenorrhea as a side effect or efficacy marker of dienogest in endometriosis treatment, not as a disease target. No publication directly investigates dienogest as a treatment for pathological amenorrhea.

Malaysia Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
(Not available)	(Not available)	(Not available)	(Not available)

6 product registrations are recorded with marketed status in Malaysia. Detailed license-level information (authorization numbers, product names, dosage forms, and approved indication text) was not available in this evidence pack.

Safety Considerations

Please refer to the package insert for safety information. Key warnings, contraindications, and drug interaction data were not available in this evidence pack.

Known data gaps (severity noted):

NPRA package insert warnings/contraindications — Blocking (required for Stage 1 safety review)
Mechanism of action (MOA) detail — High (impacts mechanistic relevance analysis)

Conclusion and Next Steps

Decision: Hold

Rationale: The top-ranked TxGNN prediction (amenorrhea) is assessed as a false positive — amenorrhea is a known and common pharmacological side effect of dienogest, not a therapeutic target. The remaining 9 predictions are similarly problematic: most involve contraindicated logic (primary ovarian failure, hypogonadotropic hypogonadism), irrelevant genetic/chromosomal conditions, or have only marginal mechanistic plausibility (breast fibrocystic disease). Additionally, critical safety data (package insert warnings, contraindications) and MOA detail are missing, blocking formal safety evaluation.

To proceed, the following is needed:

Re-evaluate model output: Flag amenorrhea, primary ovarian failure, and hypogonadotropic hypogonadism as known side effects / contraindicated associations and exclude from future candidate lists
Investigate breast fibrocystic disease (rank 3): The only prediction with limited mechanistic plausibility — requires additional literature search and expert consultation before advancing
Obtain package insert data: Download and parse NPRA-approved product inserts to complete safety profile
Query DrugBank for MOA: Retrieve detailed mechanism of action (DrugBank ID lookup needed) to enable proper mechanistic analysis
Model improvement recommendation: Consider incorporating a side-effect exclusion filter in TxGNN post-processing to reduce false-positive predictions where known adverse effects are misclassified as therapeutic indications
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.