Dydrogesterone

證據等級: L5

預測適應症: 10 個

Dydrogesterone: From Endometriosis to Amenorrhea

One-Sentence Summary

Dydrogesterone (Duphaston®) is a synthetic progestogen with over 50 years of documented clinical use in Europe and Asia for gynaecological conditions including endometriosis, dysmenorrhea, and luteal phase insufficiency. The TxGNN model predicts it may be effective for Amenorrhea, with 6 clinical trials and 6 publications currently supporting this direction. The mechanistic rationale is strong: dydrogesterone's selective progestogenic action on the endometrium is the pharmacological foundation of hormone replacement therapy (HRT) regimens routinely used to manage both primary and secondary amenorrhea — though it is not currently registered in Singapore.

Quick Overview

Item	Content
Original Indication	Gynecological disorders (endometriosis, dysmenorrhea, luteal insufficiency) — based on published literature; no Singapore registration on record
Predicted New Indication	Amenorrhea
TxGNN Prediction Score	88.53%
Evidence Level	L3
Singapore Market Status	Not marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Dydrogesterone is a synthetic progestogen that selectively binds to progesterone receptors (PR-A and PR-B) in the endometrium, triggering the transition from the proliferative phase to the secretory phase. This mechanism — progestogen opposition of estrogen-driven endometrial proliferation — is the pharmacological cornerstone of cyclic HRT worldwide. Unlike many synthetic progestogens, dydrogesterone carries no androgenic, glucocorticoid, or mineralocorticoid side-activity, making it a preferred agent for long-term gynaecological use.

Amenorrhea (both primary and secondary) frequently arises from conditions characterised by insufficient progesterone signalling: premature ovarian insufficiency (POI), hypothalamic-pituitary axis dysfunction, and Asherman's syndrome (intrauterine adhesions following uterine surgery). In all these settings, cyclic progestogen administration — commonly dydrogesterone — is standard HRT practice to restore cyclical bleeding, protect the endometrium from unopposed estrogen, and support uterine development. The 1972 French clinical review (PMID 4673267) and the 1977 German progestin therapy review (PMID 556711) both document dydrogesterone's established gynaecological role, and the 2022 Cochrane review (PMID 36200708) confirms progestogen as an essential HRT component in POI — a leading cause of secondary amenorrhea.

The TxGNN prediction therefore aligns precisely with well-established pharmacological rationale and half a century of clinical practice in Europe and Asia. The gap in evidence is not mechanistic uncertainty but rather the absence of direct head-to-head trials specifically labelled for amenorrhea as the primary endpoint, and the lack of any Singapore regulatory registration.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT06952296	N/A	Not Yet Recruiting	250	Observational multicenter study of dydrogesterone for endometriosis-associated pain; not yet started and has no results, but confirms ongoing regulatory-level interest in dydrogesterone for gynaecological indications
NCT03329898	N/A	Unknown	200	Balloon uterine stent combined with hormonal therapy (estrogen + progestogen) for Asherman's syndrome — a primary cause of secondary amenorrhea; directly relevant disease context
NCT01300676	Phase 2/3	Completed	79	Completed comparison of HRT (estrogen + progestogen including dydrogesterone) vs. Tualang honey in postmenopausal women; establishes safety profile in HRT context
NCT02726971	Phase 1/2	Completed	141	Completed RCT of estrogen dose after hysteroscopic adhesiolysis for Asherman's syndrome; sequential progestogen (e.g., dydrogesterone) is standard in such regimens
NCT03346317	N/A	Unknown	100	Asherman's syndrome therapy with balloon stent + estrogen vs. amnion graft; hormonal regimen directly relevant to secondary amenorrhea management
NCT03351205	N/A	Unknown	100	Prevention of adhesion recurrence post-hysteroscopy with estrogen and sequential progestogen; confirms multi-centre adoption of hormonal protocols for adhesion-related amenorrhea

Literature Evidence

PMID	Year	Type	Journal	Key Findings
36200708	2022	Cochrane Review	Cochrane Database Syst Rev	Systematic review of HRT for uterine and endometrial development in POI; amenorrhea is a defining feature of POI, and progestogen (including dydrogesterone) is an essential HRT component — highest-quality evidence in this pack
556711	1977	Review	Fortschritte der Medizin	German review of progestin therapy spectrum; dydrogesterone specifically recommended for endometriosis and broader reproductive gynaecological indications; early authoritative documentation of its clinical utility
4673267	1972	Clinical Review	La Nouvelle presse médicale	Earliest clinical review of dydrogesterone indications in gynaecology — documents its role in menstrual cycle-related conditions from the outset of clinical use
23185193	2012	Cohort	Archives of Medical Science	Estroprogestagen therapy (including dydrogesterone) in adolescent girls with functional hypothalamic amenorrhea (FHA); assessed impact on bone mineral density across ER-α polymorphism subtypes
34219314	2021	Case Report	J Obstet Gynaecol Res	Secondary hypopituitarism post-craniopharyngioma resection causing primary amenorrhea; sequential estrogen + progesterone (dydrogesterone component) used for endometrial support and successful conception
39901965	2025	Case Report	SAGE Open Med Case Rep	Turner syndrome presenting with primary amenorrhea and ischemic cardiomyopathy; illustrates the clinical HRT context where progestogens including dydrogesterone are integral to management

Singapore Market Information

Dydrogesterone is not currently registered in Singapore. No marketing authorisations are on record (total licences: 0).

Context for decision-makers: Dydrogesterone is marketed globally as Duphaston® (Abbott/Viatris) and holds regulatory approvals for gynaecological indications in the EU, UK, Japan, Hong Kong, Malaysia, and numerous other countries. A Singapore registration pathway via HSA (NDA or GDA submission) would need to be formally assessed before any clinical application.

Safety Considerations

Detailed safety data (package insert warnings, contraindications, and drug–drug interaction data) is not available in this Evidence Pack.

Please refer to the official package insert and current prescribing information for complete safety information. Priority areas to review before any clinical application include: risk of thromboembolic events, hepatic function in patients with hepatic impairment, contraindications in hormone-sensitive conditions, and use in pregnancy (luteal phase support versus teratogenicity data).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Dydrogesterone's progestogenic mechanism is the established pharmacological basis for managing progesterone-deficiency-related amenorrhea (POI, Asherman's syndrome post-operative HRT, and hypothalamic amenorrhea), supported by over 50 years of documented clinical use globally. Evidence is predominantly observational and indirect (L3) rather than from head-to-head amenorrhea-specific RCTs, and Singapore registration is currently absent — these are the two guardrails that must be addressed before clinical deployment.

To proceed, the following is needed:

Singapore registration: Dydrogesterone is not currently marketed in Singapore; a formal HSA NDA/GDA submission is a prerequisite for any clinical use
Full safety review (DG001): Obtain and parse the official product insert (TFDA or EMA SmPC) for contraindications, boxed warnings, and drug interactions before clinical application
MOA data (DG002): Confirm detailed mechanism of action via DrugBank API query to support the mechanistic link analysis
Targeted clinical evidence: Identify or sponsor prospective studies evaluating dydrogesterone as part of sequential HRT specifically in well-defined amenorrhea subtypes (POI, Asherman's post-hysteroscopy, hypothalamic amenorrhea) in the Singapore/Southeast Asian population
Population-specific safety assessment: Review safety data in the target demographic, including adolescents (for FHA) and women of reproductive age with POI, given the long-term HRT exposure anticipated
Disclaimer

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