Levonorgestrel
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Levonorgestrel: From Osteoporosis to Acne
One-Sentence Summary
Levonorgestrel is a progestin, best known as a contraceptive, and the knowledge graph lists postmenopausal osteoporosis and osteoporosis as its original indications. The TxGNN model predicts it may be effective for acne, but the 0 clinical trials and 19 publications compiled for this report (mostly narrative reviews) do not directly support this direction. This is a model-generated hypothesis only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Postmenopausal osteoporosis / osteoporosis (from the knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Acne (disease) |
| TxGNN Prediction Score | 99.88% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. Levonorgestrel is a progestin used in oral contraceptives, emergency contraception, implants and intrauterine systems. Sex steroids influence bone turnover, which is the only link to the original osteoporosis indication.
The mechanistic link to acne is weak. Levonorgestrel is derived from the 19-nortestosterone family and retains some androgenic activity, which could in principle worsen acne rather than treat it. Documented dermatological benefit comes mainly from combined contraceptives containing anti-androgenic progestins, such as chlormadinone acetate. One randomized, placebo-controlled trial (2002) tested a low-dose pill combining 20 µg ethinyl estradiol with 100 µg levonorgestrel in moderate acne. Any benefit there may come from the estrogen component and the combination, not from levonorgestrel alone. The high TxGNN score is therefore not supported by a plausible direct mechanism.
Clinical Trial Evidence
Currently no related clinical trials registered for acne.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12196750 | 2002 | Randomized, placebo-controlled trial | J Am Acad Dermatol | Tested an ethinyl estradiol 20 µg / levonorgestrel 100 µg pill in moderate acne; the abstract provided does not report the results, and the effect cannot be attributed to levonorgestrel alone |
| 15025547 | 2004 | Review | Drugs | Ethinylestradiol/chlormadinone acetate was significantly more effective than ethinylestradiol/levonorgestrel in mild-to-moderate papulopustular acne |
| 21895044 | 2011 | Review | Am J Clin Dermatol | Dermatological benefits of an anti-androgenic progestin combination for acne, hirsutism, seborrhea and hair loss |
| 30088446 | 2018 | Review | Curr Drug Targets | Molecular interactions of steroids in sebum production |
| 7825629 | 1995 | Review | Am J Med | Androgenicity of progestins, including 19-carbon progestins such as levonorgestrel |
| 32909630 | 2020 | Systematic review | Cochrane Database Syst Rev | Levonorgestrel-releasing intrauterine system for endometrial hyperplasia (not acne-related) |
| 14688179 | 2004 | Clinical study | Hum Reprod | Intrauterine levonorgestrel for symptomatic treatment of endometriosis (not acne-related) |
| 11727177 | 2001 | Review | Semin Reprod Med | Progestin-releasing intrauterine systems for contraception |
The remaining retrieved publications are general reviews of contraception (implants, IUDs, oral contraceptives) and are not specific to acne.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11836P | POSTINOR 2 TABLET 0.75 mg | Tablet | Not stated in the data compiled |
| SIN07915P | MIRENA Levonorgestrel Intrauterine System 20 mcg/24 hr | Intrauterine device | Not stated in the data compiled |
| SIN04834P | MICROGYNON 30 TABLET | Sugar-coated tablet | Not stated in the data compiled |
Safety Considerations
- Contraindications (from the knowledge graph, not label text): hypertension, epilepsy, anxiety and neurotic disorders, dysthymic disorder, porphyria, kidney disease, liver disease, gallbladder disease, hyperglycemia, diabetes mellitus and diabetic ketoacidosis, hypothyroidism, systemic lupus erythematosus, asthma, blood coagulation disease, hypertriglyceridemia, and hypercalcemia-related conditions.
- Drug Interactions: 100 interactions were found. The 20 listed are all moderate severity. Main groups: glucose-lowering drugs (acarbose, canagliflozin, dapagliflozin, ertugliflozin, exenatide, liraglutide, linagliptin, nateglinide, and multiple insulins), plus aprepitant, clotrimazole, glycerol phenylbutyrate and linaclotide.
- Package insert warnings were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on model output with no registered trials. The retrieved literature is mostly narrative reviews. Levonorgestrel's residual androgenicity argues against a direct anti-acne effect, and the only acne-specific evidence involves combination pills. Other predicted indications (ranks 2–10) have no efficacy evidence either. The lactation disease prediction is supported only by a contraceptive safety study, not by evidence of therapeutic benefit.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Singapore Health Sciences Authority (HSA), which are required for safety screening
- Mechanism of action data
- Review of the 2002 EE/levonorgestrel acne trial to separate the effect of levonorgestrel from that of ethinyl estradiol
- Comparison with established anti-androgenic hormonal options for acne
- Evidence that benefits outweigh the contraindications and interaction risks listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.