Levonorgestrel
| Evidence Level: L2 | Predicted Indications: 5 |
Table of Contents
Levonorgestrel: Acne (disease)
One-Sentence Summary
Levonorgestrel is a synthetic progestin, a hormone-like drug that acts on progesterone receptors. The TxGNN model predicts it may be useful for acne (score 0.9988). The compiled data contain no registered clinical trials and 19 publications for this prediction. Only one publication is a randomised placebo-controlled trial, and it tested an oral contraceptive combining levonorgestrel with ethinyl estradiol, so it does not isolate levonorgestrel’s own effect. The evidence level is L2.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Acne (disease) |
| TxGNN Prediction Score | 0.9988 |
| Evidence Level | L2 |
| 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 |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not currently available for levonorgestrel. It is a progestin with some residual androgenic (male-hormone-like) activity (PMID 7825629). In theory this is a concern for acne rather than a benefit, because androgens stimulate the oil glands of the skin.
Dermatological benefit in acne is documented mainly for combined oral contraceptives that contain progestins with anti-androgenic properties, such as chlormadinone acetate (PMIDs 21895044, 15025547). In one review, a chlormadinone-containing pill was reported to be more effective for mild-to-moderate acne than an ethinyl estradiol/levonorgestrel pill.
A randomised placebo-controlled trial (PMID 12196750) did test a low-dose pill containing ethinyl estradiol 20 µg and levonorgestrel 100 µg in moderate acne. In that product, the estrogen component may contribute to any benefit.
The high TxGNN score probably reflects the drug’s similarity to hormonal contraceptives as a class. It is not evidence of a direct benefit from levonorgestrel. Any effect on acne may be indirect and could be neutral or adverse, depending on the formulation. Acne has been reported as a side effect of levonorgestrel-releasing intrauterine systems and implants.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12196750 | 2002 | RCT | J Am Acad Dermatol | Randomised, placebo-controlled trial of a low-dose pill (ethinyl estradiol 20 µg + levonorgestrel 100 µg) in moderate acne. The product improves biochemical markers of androgenicity. Outcome data were not available in the abstract excerpt compiled. |
| 15025547 | 2004 | Review | Drugs | Ethinylestradiol/chlormadinone acetate was significantly more effective than ethinylestradiol/levonorgestrel for mild-to-moderate facial papulopustular acne. |
| 21895044 | 2011 | Review | Am J Clin Dermatol | Dermatological benefits of an anti-androgenic combined pill in acne, hirsutism, seborrhoea and female pattern hair loss. |
| 30088446 | 2018 | Review | Curr Drug Targets | Molecular interactions of steroids in sebum production, with acne as a key related disease. |
| 7825629 | 1995 | Review | Am J Med | Describes the androgenicity of progestins, including 19-carbon progestins such as levonorgestrel. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11909T | Kyleena | Intrauterine drug delivery system 19.5 mg | Not available in the data compiled |
Safety Considerations
- Drug Interactions: The data compiled for this report list 100 interacting drugs, all at moderate level in the entries reviewed. Examples include:
- blood-glucose-lowering agents: acarbose, canagliflozin, dapagliflozin, ertugliflozin, exenatide, liraglutide, linagliptin, nateglinide, and several insulins
- others: aprepitant, clotrimazole, glycerol phenylbutyrate, linaclotide
Please refer to the TGA-approved Product Information (PI) for warnings, contraindications and full interaction information.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence level is L2, based on one randomised placebo-controlled trial. That trial tested a levonorgestrel and ethinyl estradiol combination, not levonorgestrel alone. Levonorgestrel’s residual androgenic activity, and acne reports with some levonorgestrel formulations, argue against assuming benefit from the drug itself.
To proceed, the following is needed:
- Detailed mechanism of action data
- Trial results separating levonorgestrel’s effect from that of ethinyl estradiol, ideally for the formulations marketed in Australia
- Safety data from the TGA-approved Product Information (PI), including warnings and contraindications
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.