Levonorgestrel

證據等級: L5

預測適應症: 6 個

Levonorgestrel: From Contraception to Acne (Disease)

One-Sentence Summary

Levonorgestrel is a synthetic progestin widely used in hormonal contraceptive products (oral contraceptives, IUDs, implants). The TxGNN model predicts it may be effective for Acne (disease), with 5 clinical trials and 20 publications currently retrieved for this drug-disease pair — though only a subset directly addresses acne as a primary outcome.

Quick Overview

Item	Content
Original Indication	No approved-indication text available (drug is not marketed in this jurisdiction; no license records)
Predicted New Indication	Acne (disease)
TxGNN Prediction Score	99.88%
Evidence Level	L2
US Market Status	Not Marketed
Number of NDAs	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available for Levonorgestrel. Based on the evidence retrieved, Levonorgestrel is a synthetic 19-nortestosterone-derived progestin used across hormonal contraceptive platforms (combined oral contraceptives, progestin-only implants, and the levonorgestrel-releasing intrauterine system). Its efficacy in contraception is well established, and the literature base consistently describes androgenic activity as an inherent property of this drug class.

The link to acne is mechanistic rather than indication-adjacent: several retrieved publications (e.g., PMID 12196750, PMID 10717776) directly studied levonorgestrel-containing combined oral contraceptives and their effect on androgenic markers and acne severity, since androgens are known drivers of acne pathophysiology. Other combined hormonal products with antiandrogenic progestins (e.g., chlormadinone acetate, drospirenone) have documented dermatological benefits including acne improvement, which is used in the literature as a comparator to levonorgestrel-containing regimens (PMID 21895044, PMID 15025547, PMID 16796485). This suggests the acne signal is plausible but is tied to specific combined-hormone formulations rather than levonorgestrel monotherapy, and the direction of effect (levonorgestrel is comparatively more androgenic than antiandrogenic progestins) requires careful interpretation before further development.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00161226	N/A	Terminated	44	LNG-IUS (Mirena) studied for endometrial cancer prevention in obese women; oral progestin side effects (including acne) noted as background rationale, not a primary acne outcome
NCT01650168	N/A	Completed	101,498	Large safety cohort comparing nomegestrol acetate/estradiol vs. levonorgestrel-containing combined oral contraceptives; not acne-focused
NCT00480532	N/A	Completed	131	Doxycycline added to continuous oral contraception to reduce breakthrough bleeding; acne mentioned only as an example doxycycline indication
NCT05570786	Phase 2	Completed	100	Subdermal gestrinone implant for endometriosis-related pelvic pain; not levonorgestrel- or acne-specific
NCT05492487	Phase 2	Unknown	60	LNG-IUS (Mirena) vs. megestrol for fertility-sparing treatment of atypical endometrial hyperplasia; not acne-related

Note: none of the retrieved trials use acne as a primary endpoint; relevance to the predicted indication is weak and largely incidental.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
12196750	2002	RCT	J Am Acad Dermatol	Randomized, placebo-controlled trial of ethinyl estradiol/levonorgestrel (20/100 mcg) showing efficacy for moderate acne
10717776	1999	RCT	Contraception	Multicenter randomized study comparing androgenic markers and acne outcomes across low-dose OC progestins including levonorgestrel
21895044	2011	Review	Am J Clin Dermatol	Reviews dermatological (acne, hirsutism, seborrhea) benefits of antiandrogenic hormonal contraceptive components
15025547	2004	Review	Drugs	Ethinylestradiol/chlormadinone acetate shown more effective than ethinylestradiol/levonorgestrel for papulopustular acne
16796485	2006	Review	J Womens Health	Reviews drospirenone vs. levonorgestrel/medroxyprogesterone regarding acne and hirsutism outcomes
7825629	1995	Review	Am J Med	Reviews progestin androgenicity, the mechanistic basis for progestin-related acne effects
32909630	2020	Systematic Review	Cochrane Database Syst Rev	Cochrane review of levonorgestrel-releasing intrauterine system for endometrial hyperplasia (background/mechanism reference, not acne)
11727177	2001	Review	Semin Reprod Med	Overview of levonorgestrel-releasing intrauterine system pharmacology and endometrial effects
1773615	1991	Review	Contraception	Evaluation of levonorgestrel-releasing IUD versus copper IUDs
8489751	1993	Review	Ann Med	Review of hormonal intrauterine devices releasing levonorgestrel

US Market Information

No FDA/NDA license records were retrieved for Levonorgestrel in this Evidence Pack (total_licenses: 0, market status: Not Marketed).

Safety Considerations

Please refer to the package insert for safety information. No warnings, contraindications, or drug-interaction data were retrieved for this evaluation (DDI query status: not found).

Conclusion and Next Steps

Decision: Hold

Rationale:

The predicted acne indication is supported by plausible mechanism and several published RCTs, but no clinical trial directly tests levonorgestrel for acne, and safety data (warnings, contraindications, DDI) are completely missing — a blocking gap that prevents entry into the S1 safety pre-assessment stage.

To proceed, the following is needed:

TFDA/FDA package insert warnings and contraindications (DG001, blocking)
Confirmed mechanism of action data (DG002)
A dedicated review of whether levonorgestrel’s androgenic profile helps or worsens acne relative to antiandrogenic comparators cited in the literature, given the mixed direction of evidence
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.