Estriol
| Evidence Level: L3 | Predicted Indications: 1 |
Table of Contents
Estriol: From Menopausal Hormone Therapy to Amenorrhea
One-Sentence Summary
Estriol is a weak estrogen receptor agonist marketed in India as oral tablets and vaginal creams. It has long been used in Europe and Asia for post-menopausal hot flashes. The TxGNN model predicts it may be effective for amenorrhea, with no registered clinical trials and 6 publications (only 2 directly relevant) currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in the India licence records (the pharmacology data lists post-menopausal hot flashes as its use in Europe and Asia) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 0.9918 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (5 of 5) – CDSCO approval status is not included in this data |
| Number of Listed Products | 5 (valid: 5) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Pharmacology data shows that estriol binds estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2). It is a weak estrogen agonist.
The predicted indication is amenorrhea, particularly functional hypothalamic amenorrhea (FHA). In FHA, the hypothalamus releases GnRH in an impaired pattern. This leaves the body in a low-estrogen state with reduced ovarian function. Low-dose estrogen replacement may act as a neuroendocrine modulator. It may help restore feedback on LH secretion and support endometrial and bone health.
Two publications support this idea. A 2012 study (PMID 22137494) reports that estriol administration modulates LH secretion in women with FHA. A 2023 review (PMID 37371858) proposes a similar putative mechanism for low-dose estrogens. The high TxGNN score is consistent with this rationale, but it is a computational prediction, not clinical evidence. Mechanistic plausibility is good. However, no controlled data show that estriol restores menses or ovulation.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22137494 | 2012 | Clinical study (small physiological study, not an RCT) | Fertility and Sterility | Evaluated how estriol affects hypothalamus-pituitary function and gonadotropin secretion in FHA patients; reports modulation of LH secretion |
| 37371858 | 2023 | Review | Biomedicines | Proposes low-dose estrogens as neuroendocrine modulators in FHA, possibly triggering positive feedback mechanisms |
| 5935707 | 1966 | Case series | Am J Obstet Gynecol | Prolonged amenorrhea after medroxyprogesterone in pregnancy; indirect, not estriol-specific |
| 14194444 | 1964 | Clinical trial | J Obstet Gynaecol Br Commonw | Human gonadotrophins in idiopathic secondary amenorrhoea; historical, indirect |
| 13931724 | 1963 | Review | J Clin Endocrinol Metab | Mechanisms of anti-ovulatory compounds; historical, indirect |
| 979592 | 1976 | Methods/Review | Die Medizinische Welt | Radioimmunoassay for hormone measurement; not therapeutic evidence |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 72332 | Evalon Cream | Vaginal cream, tube of 15 gm | Not stated |
| 233909 | Vagimoist Vaginal Cream | Vaginal cream, tube of 15 gm | Not stated |
| 73078 | Evalon 2mg Tablet | Tablet, strip of 30 | Not stated |
| 72964 | Evalon 1mg Tablet | Tablet, strip of 30 | Not stated |
| 72888 | Evolon Cream | Vaginal cream, tube of 15 gm | Not stated |
Safety Considerations
Please refer to the package insert for safety information.
Pharmacology data confirms that estriol acts on estrogen receptor alpha (ESR1) and beta (ESR2). No drug-drug interactions with specific interacting drugs are listed.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is biologically plausible and has a high model score. However, direct evidence is limited to one small physiological study and one review, with no registered clinical trials and no controlled efficacy data. Package insert safety information is also missing.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India regulatory source
- Approved indication text for the Indian licences
- Detailed mechanism of action data
- Controlled clinical studies of estriol in amenorrhea (especially FHA), with menses and ovulation outcomes
- Route compatibility assessment: the Indian products are oral tablets and vaginal creams, and the route best suited to amenorrhea needs to be determined
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.