Progesterone
| Evidence Level: L4 | Predicted Indications: 6 |
Table of Contents
Progesterone: Breast fibrocystic disease
One-Sentence Summary
Progesterone is a natural female sex hormone (a progestogen) that is marketed in Canada in several single-ingredient products. The TxGNN model predicts it may be useful for breast fibrocystic disease, with a prediction score of 0.9998.
Support is thin: there are 0 registered clinical trials and 20 publications. These are mostly reviews, older endocrine studies and observational work, with no direct evidence that progesterone improves outcomes.
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 |
| Canada Market Status | Marketed (marketed DINs: 12 of 12) |
| Number of DINs | 12 (marketed: 12) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for progesterone is not available in the data compiled for this report. The rationale below therefore rests on the published literature on the disease itself.
Fibrocystic breast changes are the most common benign breast condition. They are thought to arise from excessive cell proliferation in response to the monthly shifts in estrogen and progesterone. One review (Vorherr, 1986) describes the pathophysiology as estrogen predominance with progesterone deficiency, driving hyperproliferation of connective tissue and then of epithelium. A study of 50 women with the condition and 40 controls examined the estradiol-to-progesterone (E2/P) ratio in the late luteal phase, supporting the idea that hormone balance matters.
If relative progesterone deficiency contributes to the disease, supplementing progesterone is a plausible hypothesis. However, the evidence is mechanistic and descriptive. No interventional study of progesterone in this condition was found, so this remains a research question rather than a demonstrated benefit.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28598826 | 2017 | Randomized trial (metformin, not progesterone) | Breast Disease | Double-blind placebo-controlled trial of metformin in fibrocystic changes, chosen for its antiproliferative effect. It addresses the disease but not progesterone. |
| 31168213 | 2018 | Observational (50 cases vs 40 controls) | Acta Clinica Croatica | Examined the late-luteal estradiol/progesterone relationship in women with fibrocystic breast disease versus controls. |
| 3511705 | 1986 | Review | Am J Obstet Gynecol | Describes the disease as driven by estrogen predominance and progesterone deficiency. Notes a two- to fourfold increase in breast cancer risk. |
| 6481706 | 1984 | Review | J Reprod Med | Reviews how estrogen and progesterone relate to benign and malignant breast disease. Concludes that oral contraceptives may be slightly protective. |
| 1936311 | 1991 | Review | Fertil Steril | Earlier oral contraceptives appeared to protect against most benign breast disease. It is unclear whether current low-dose progestogen products do the same. |
| 41438397 | 2025 | Cross-sectional | Int J Reprod Biomed | Studied the association between fibrocystic breast disease and polycystic ovary syndrome phenotypes. |
| 7788004 | 1995 | Cohort | Eur J Endocrinol | Measured thyroid hormones in serum and breast cyst fluid of women with fibrocystic disease. |
| 3902125 | 1985 | Review | Breast Cancer Res Treat | Review of the epidemiology and endocrinology of benign breast disease. |
| 34537861 | 2022 | Pathology review | Virchows Arch | Reviews apocrine change in benign, atypical and malignant breast lesions. It is diagnostic in focus. |
| 22103710 | 2012 | Observational | Gynecol Endocrinol | Compared fibrocystic breast disease rates across PCOS phenotypes against hormonal and metabolic parameters. |
Canada Market Information
Progesterone has 12 valid licences in Canada. The approved indication text is not recorded in the local data. Five of the licences are shown below.
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02531828 | Progesterone Injection, USP | Not specified | Not specified |
| 02551268 | M-Progesterone | Not specified | Not specified |
| 02493578 | Auro-Progesterone | Not specified | Not specified |
| 02241013 | Crinone | Not specified | Not specified |
| 02166704 | Prometrium | Not specified | Not specified |
Safety Considerations
- Drug Interactions: 100 interactions are recorded. The examples reviewed are all rated Moderate. They include:
- antidiabetic agents: acarbose, metformin, pioglitazone, glimepiride, repaglinide, chlorpropamide, alogliptin, saxagliptin, canagliflozin, dapagliflozin and empagliflozin
- GLP-1 agonists: semaglutide, liraglutide, dulaglutide and albiglutide
- insulins: insulin aspart, degludec and detemir
- others: aprepitant and clarithromycin
- Conditions flagged for caution: The data compiled for this report links progesterone with caution in several conditions. These come from disease-level associations, not label text. They include hypertension, liver disease and liver failure, kidney disease, diabetes mellitus, epilepsy, asthma, porphyria, hypothyroidism, systemic lupus erythematosus and hypertriglyceridemia.
Label warnings and contraindications were not captured, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The hormonal rationale for breast fibrocystic disease is plausible and progesterone is widely marketed in Canada. However, the evidence is limited to reviews and observational or mechanistic studies. There are no registered trials and no direct interventional data for progesterone. The label safety information has also not yet been captured.
To proceed, the following is needed:
- Controlled clinical evidence (a randomized trial or well-designed prospective study) of progesterone in this condition
- Mechanism-of-action data for the drug
- Health Canada package insert warnings and contraindications, reviewed for a benign-breast-disease population
- Route and dosage form assessment (topical or oral) suited to breast symptoms
- A review of the interaction profile, especially with antidiabetic therapy
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.