Dienogest

證據等級: L5

預測適應症: 10 個

Dienogest: From Endometriosis to Amenorrhoea

One-Sentence Summary

Dienogest is a fourth-generation synthetic progestin, approved internationally (as Visanne®, Bayer) for the treatment of endometriosis, but currently not registered with the Therapeutic Goods Administration (TGA) in Australia. The TxGNN model predicts it may have clinical relevance to Amenorrhoea, with 4 clinical trials and 6 publications identified — however, the available evidence consistently frames amenorrhoea as a pharmacological side effect of endometriosis treatment rather than an independent therapeutic indication. Evidence is rated L4 (mechanistic/indirect), and a Hold decision is recommended.

Quick Overview

Item	Content
Original Indication	Endometriosis (internationally approved; not registered with TGA in Australia)
Predicted New Indication	Amenorrhoea
TxGNN Prediction Score	99.71%
Evidence Level	L4
Australia Market Status	Not marketed
Number of ARTG Entries	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data is not currently available in this Evidence Pack. Based on information derived from clinical trial summaries and the accompanying pharmacological literature, Dienogest is a fourth-generation synthetic progestin with highly selective progesterone receptor affinity (relative binding affinity approximately 71% compared with progesterone). It inhibits ovulation, suppresses serum estradiol to near-castrate levels (<30 pg/mL), and inhibits endometrial proliferation. These combined actions are well-recognised to induce amenorrhoea or irregular spotting, with reported amenorrhoea rates of 20–30% during long-term use.

The mechanistic link to amenorrhoea is therefore pharmacologically coherent. However, a critical directional distinction must be noted: Dienogest is a cause of amenorrhoea (through hypothalamic-pituitary-ovarian axis suppression) rather than a treatment for amenorrhoea as a disease entity. In current clinical practice, amenorrhoea is typically regarded as a desired secondary outcome — or a manageable adverse effect — of endometriosis therapy, not the registered therapeutic target.

If the repurposing question is reframed more specifically as “using Dienogest to induce amenorrhoea for the management of abnormal uterine bleeding (AUB),” there is indirect mechanistic support and some observational data. However, no independent RCT has been conducted with amenorrhoea induction as the primary endpoint and registered indication. This framing gap, combined with the absence of TGA registration, represents the primary barrier to clinical translation in Australia.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT07164183	Phase 3	Recruiting	290	Prospective, multicentre, open-label randomised parallel-group non-inferiority study comparing Indinol Forto® 200 mg vs Visanne® 2 mg for endometriosis; highest methodological rigour among identified trials — amenorrhoea rate likely a monitored secondary endpoint
NCT07204093	N/A	Active, not recruiting	138	Compares transdermal estradiol + dienogest versus drospirenone combinations for endometriosis HRT management; menstrual pattern outcomes (including amenorrhoea induction and breakthrough bleeding) likely observed
NCT04495855	N/A	Completed	968	VISANNE OS real-world observational study of dienogest for endometriosis in routine clinical practice across multiple sites; amenorrhoea documented as a secondary safety-reporting item, not a primary efficacy endpoint
NCT02425462	N/A	Completed	895	VISION Asia prospective observational cohort assessing effectiveness and long-term safety of dienogest in Asian women with endometriosis; amenorrhoea captured as part of safety surveillance, not therapeutic outcome

⚠️ Clinical note: None of the identified trials investigated amenorrhoea as a primary therapeutic indication. Across all four studies, amenorrhoea appears exclusively as a secondary or safety-monitoring endpoint in the context of endometriosis treatment.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
39090694	2024	Systematic Review + Bayesian Meta-analysis	BMC Pharmacology & Toxicology	Comprehensive Bayesian analysis of adverse effects of dienogest in endometriosis and adenomyosis; quantifies prevalence of amenorrhoea as a frequently occurring adverse event and provides population-level estimates for informed consent
41329046	2026	Pharmacological / In Vitro Study	Eur J Contracept Reprod Health Care	Confirms high inhibition ratio and transformation index of dienogest 2 mg; mechanistically demonstrates dienogest’s capacity to induce amenorrhoea through hypoestrogenic environment — directly supports TxGNN prediction rationale
34405378	2022	Narrative Review	Reviews in Endocrine & Metabolic Disorders	Comprehensive overview of hormonal treatments for endometriosis, including endocrine mechanisms underpinning progestin-induced amenorrhoea, estrogen dependency, and progesterone resistance
29161960	2018	Prospective Cohort	Reproductive Sciences	Multicentre retrospective cohort (n=514) assessing long-term efficacy and safety of dienogest in ovarian endometrioma beyond 12 months; amenorrhoea rates documented across extended treatment duration

Australia Market Information

Dienogest is not currently registered with the TGA and has no entries on the Australian Register of Therapeutic Goods (ARTG). No TGA-approved Product Information document is available for this medicine in Australia.

Clinicians seeking prescribing information should refer to international regulatory sources, such as:

EMA Summary of Product Characteristics (SmPC) for Visanne® 2 mg tablets (dienogest) — approved in the European Union for endometriosis
PMDA (Japan) or MFDS (South Korea) product monographs, where Dienogest has established regulatory approval

Any clinical use in Australia would need to occur through the TGA’s Special Access Scheme (SAS) or Authorised Prescriber pathway, both of which require documented clinical justification.

Safety Considerations

As Dienogest is not currently registered in Australia, no TGA-approved Product Information is available. Please refer to the relevant international Product Information documents (EMA SmPC or equivalent) for full safety, contraindication, and drug interaction data prior to any clinical consideration.

International sources indicate that clinically relevant safety considerations for Dienogest typically include: effects on bone mineral density with long-term use, irregular uterine bleeding patterns, impact on mood and libido, and interactions with CYP3A4 inducers/inhibitors. Formal safety review against a TGA or EMA source is recommended before any clinical decision-making.

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN model has correctly identified a genuine pharmacological relationship — Dienogest does suppress the hypothalamic-pituitary-ovarian axis and reliably induces amenorrhoea through its progestogenic mechanism. However, the entire evidence base positions amenorrhoea as a consequence of endometriosis treatment rather than a primary therapeutic target, and the drug is not registered on the ARTG. Both the evidence framing and the regulatory gap must be resolved before progression.

To proceed, the following is needed:

Regulatory pathway assessment: Evaluate TGA registration options (full registration, SAS Category B/C, or Authorised Prescriber) for Dienogest in Australia, including identification of the most clinically appropriate indication framing
Safety data retrieval: Download and review the EMA SmPC (or equivalent national PI) to complete the safety, contraindication, and drug-drug interaction profile — currently a blocking data gap
MOA documentation: Retrieve full mechanism of action details from DrugBank (DB09123) or primary pharmacology literature to support future indication submissions
Indication reframing: If the clinical intent is amenorrhoea induction for abnormal uterine bleeding (AUB) management, a targeted literature search under AUB/heavy menstrual bleeding (HMB) terminology is required to identify more directly relevant evidence
Primary endpoint RCT review: Conduct a systematic review to confirm whether any completed or ongoing RCT has registered amenorrhoea induction as a primary efficacy endpoint for Dienogest — if not, this would confirm an evidence gap suitable for investigator-initiated trial design

Disclaimer: This report is intended for research reference purposes only and does not constitute medical advice. Drug repurposing candidates require clinical validation before any therapeutic application. All content should be reviewed in conjunction with current TGA guidelines and local institutional policies.

Disclaimer

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