Progesterone
| Evidence Level: L4 | Predicted Indications: 6 |
Table of Contents
Progesterone: Breast fibrocystic disease
One-Sentence Summary
Progesterone is a natural progestogen hormone that is marketed in Australia. The TxGNN model predicts it may be useful for breast fibrocystic disease. The data compiled for this report contain no clinical trials and 19 publications on the condition, mostly observational, pathological or review-level. None of them tests progesterone as a treatment, so support is limited to a hormonal rationale.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Breast fibrocystic disease |
| TxGNN Prediction Score | 0.9998 |
| Evidence Level | L4 |
| Australia Market Status | Listed on the PBS Schedule (2 of 2 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 2 (valid: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for progesterone are not available in the data compiled for this report. The rationale therefore rests on the hormonal biology of the breast.
Fibrocystic changes are hormone-responsive. A 1986 review proposed that the condition is driven by estrogen predominance with relative progesterone deficiency, leading to excess connective tissue and epithelial proliferation. A smaller case-control study of women with the condition, in the late luteal phase, examined the estradiol-to-progesterone ratio, supporting interest in this hormonal balance.
This is a hypothesis, not proof of benefit. The literature is observational, pathological or review-level, and much of it is dated. It contains no interventional data on progesterone. Reviews of oral contraceptives and benign breast disease describe combined hormonal effects, not progesterone alone.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28598826 | 2017 | RCT | Breast Disease | Double-blind, placebo-controlled trial of metformin (not progesterone) in fibrocystic changes, based on its antiproliferative action |
| 31168213 | 2018 | Case-control | Acta Clinica Croatica | Compared late-luteal estradiol/progesterone ratio in 50 women with the condition and 40 controls |
| 41438397 | 2025 | Cross-sectional | Int J Reprod Biomed | Examined the association between fibrocystic breast disease and polycystic ovary syndrome phenotypes |
| 22103710 | 2012 | Observational | Gynecol Endocrinol | Assessed fibrocystic breast disease rates across PCOS phenotypes and hormonal and metabolic parameters in 132 women |
| 7788004 | 1995 | Observational | Eur J Endocrinol | Measured thyroid hormones in serum and breast cyst fluid of women with the condition |
| 3511705 | 1986 | Review | Am J Obstet Gynecol | Describes pathophysiology as estrogen predominance with progesterone deficiency; also covers clinical picture and management |
| 1936311 | 1991 | Review | Fertil Steril | Oral contraceptives and breast disease; earlier formulations appeared protective against benign breast disease, with uncertainty for low-dose progestogen products |
| 6481706 | 1984 | Review | J Reprod Med | Review of estrogen and progesterone in relation to breast disease |
| 3902125 | 1985 | Review | Breast Cancer Res Treat | Epidemiology and endocrinology of benign breast disease |
| 34537861 | 2022 | Review | Virchows Arch | Apocrine lesions of the breast; descriptive pathology with no treatment data |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10116K | Endometrin | Vaginal tablet 100 mg | Not available in the data compiled for this report |
| ARTG 14720R | Estrogel Pro | Pack with 30 capsules of micronised progesterone 100 mg and estradiol transdermal gel 750 micrograms per 1.25 g dose (64 doses) | Not available in the data compiled for this report |
Both entries are currently valid. Estrogel Pro is a co-packaged product with estradiol, so its licence does not describe progesterone alone.
Safety Considerations
Drug Interactions: 100 interactions are recorded, and the entries reviewed are all rated Moderate. The main ones involve:
- Antidiabetic agents: acarbose, metformin, pioglitazone, glimepiride, repaglinide, chlorpropamide, alogliptin, saxagliptin, canagliflozin, dapagliflozin, empagliflozin, semaglutide, liraglutide, dulaglutide, albiglutide, and insulins (aspart, degludec, detemir)
- Others: aprepitant and clarithromycin
For warnings and contraindications, please refer to the TGA-approved Product Information (PI).
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but the supporting evidence is a hormonal hypothesis backed by observational, pathological and review-level literature. There are no clinical trials, and no study tests progesterone as a treatment for breast fibrocystic disease. This stage is best treated as a research question.
To proceed, the following is needed:
- Interventional data (randomised or well-designed comparative studies) of progesterone in breast fibrocystic disease
- Detailed mechanism-of-action data for progesterone
- Review of the Australian Product Information for safety, especially for use in breast conditions and interactions with antidiabetic agents
- Confirmation of a suitable formulation and route for the target condition
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.