Estriol
| Evidence Level: L3 | Predicted Indications: 1 |
Table of Contents
- Estriol
- Pharmacist Assessment Report
- Estriol: Amenorrhea (disease)
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Other Predicted Indications (Brief Note)
- Conclusion and Next Steps
- Disclaimer
Estriol: Amenorrhea (disease)
One-Sentence Summary
Estriol is a weak natural oestrogen. In Australia it is marketed as a vaginal cream (Ovestin). The TxGNN model predicts it may be effective for amenorrhoea (most plausibly functional hypothalamic amenorrhoea), with no registered clinical trials but 6 publications retrieved, of which only 2 are directly relevant (one small physiological study and one review).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Amenorrhea (disease) |
| TxGNN Prediction Score | 0.9918 |
| Evidence Level | L3 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold (treat as a research question) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Pharmacology records show that estriol binds both oestrogen receptor-α (ESR1) and oestrogen receptor-β (ESR2). It is a weak oestrogen receptor agonist. It has been marketed in Europe and Asia for more than 40 years for post-menopausal hot flushes.
In functional hypothalamic amenorrhoea (FHA), stress, low energy availability or both disrupt pulsatile GnRH release. This leads to low LH and FSH, reduced ovarian function and a low-oestrogen state. Low-dose oestrogens may act as neuroendocrine modulators and influence LH secretion. A 2012 study reported that estriol modulated LH secretion in women with FHA. A 2023 review proposed a mechanistic rationale for low-dose oestrogens in FHA.
This evidence is small and physiological. It does not show that estriol restores menstruation or improves clinical outcomes. The prediction applies to “amenorrhoea” broadly, but the supporting literature concerns FHA only.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22137494 | 2012 | Small interventional physiology study | Fertility and Sterility | Evaluated the effect of estriol on hypothalamic-pituitary function and gonadotropin secretion in women with FHA. Reported modulation of LH secretion. |
| 37371858 | 2023 | Review | Biomedicines | Proposes low-dose oestrogens as neuroendocrine modulators in FHA, with a possible role in triggering positive feedback mechanisms. |
| 5935707 | 1966 | Case series | Am J Obstet Gynecol | Prolonged gynaecological and endocrine effects after medroxyprogesterone in pregnancy. Not estriol-specific. |
| 14194444 | 1964 | Clinical trial | J Obstet Gynaecol Br Commonw | Gonadotrophins in idiopathic secondary amenorrhoea. Not estriol-specific. |
| 13931724 | 1963 | Review | J Clin Endocrinol Metab | Mechanism of action of anti-ovulatory compounds. Limited relevance. |
| 979592 | 1976 | Methods/assay | Med Welt | Radioimmunoassay of LH, FSH and steroid hormones. Not therapeutic evidence. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 13926Y | Ovestin | Vaginal cream, 1 mg per g, 15 g | Not listed in the data compiled for this report |
Safety Considerations
- Drug interactions: The interaction records compiled for this report are pharmacological target records (estriol binding oestrogen receptor-α and receptor-β), not drug-drug interactions.
- Route consideration: The only Australian product is a vaginal cream. The FHA evidence used oestrogen administration that may differ in route and dose. Route compatibility has not been assessed.
- Theoretical concerns: Exogenous oestrogen is associated with proliferative effects on breast tissue, which matters for the lower-ranked breast-related predictions. Oestrogens also generally suppress lactation.
Please refer to the TGA-approved Product Information (PI) for full warnings, contraindications and interaction information.
Other Predicted Indications (Brief Note)
The other top-10 predictions are weaker. All were rated Hold.
Conclusion and Next Steps
Decision: Hold (treat as a research question)
Rationale: The prediction score is high, and there is a plausible neuroendocrine rationale and one small physiological study in FHA. However, there are no registered trials, no outcome data such as return of menses, and the only Australian product is a vaginal cream with no recorded indication in the data compiled for this report. The evidence level is L3 at best.
To proceed, the following is needed:
- The TGA-approved Product Information (warnings, contraindications and approved indications), as safety screening cannot proceed without it
- Detailed mechanism of action data, for example from DrugBank
- Clarification of which amenorrhoea subtype (for example FHA) is being targeted
- Assessment of whether vaginal administration is suitable, or whether another route or formulation is needed
- Controlled clinical studies with clinical outcomes such as menstrual recovery, bone health and endometrial safety
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.