Levonorgestrel

證據等級: L5

預測適應症: 10 個

Levonorgestrel: From Contraception to Acne

One-Sentence Summary

Levonorgestrel is a synthetic progestin whose established use — as reflected throughout the literature in this evidence pack — is hormonal contraception (oral pills, IUDs, subdermal implants, and emergency contraception). The TxGNN model predicts it may be effective for Acne, but the supporting evidence is weak and partly contradictory: 5 clinical trials and 20 publications were retrieved, yet only a handful directly address levonorgestrel and acne, and the mechanistic direction is questionable.

Quick Overview

Item	Content
Original Indication	Not available from TGA/ARTG licence data (0 licences on record in this pack). Literature within the pack indicates levonorgestrel’s established use is hormonal contraception (oral, IUD, implant, emergency contraception).
Predicted New Indication	Acne
TxGNN Prediction Score	99.88%
Evidence Level	L4
Australia Market Status	Not marketed (per this evidence pack — 0 ARTG entries; recommend independent verification against the ARTG, as levonorgestrel is a long-established molecule)
Number of ARTG Entries	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for levonorgestrel is not available in this evidence pack (flagged as a High-severity data gap). Based on the literature retrieved, levonorgestrel is a 19-nortestosterone-derived progestin with notably androgenic activity compared with other progestins (PMID 7825629, “The androgenicity of progestins”).

This is where the prediction becomes questionable rather than reinforcing. Acne treatment with hormonal agents typically relies on progestins with low or anti-androgenic activity (e.g., drospirenone, chlormadinone acetate, cyproterone), which lower bioavailable androgens at the pilosebaceous unit. Levonorgestrel’s androgenic profile points in the opposite direction — it may aggravate rather than improve acne. Supporting this concern, PMID 15025547 reports that an ethinylestradiol/chlormadinone acetate combination was significantly more effective than ethinylestradiol/levonorgestrel in treating mild-to-moderate acne, and PMID 16796485 notes that levonorgestrel (unlike drospirenone) is associated with acne vulgaris and hirsutism rather than their reduction.

The one directly relevant RCT (PMID 12196750) did find that a low-dose ethinylestradiol/levonorgestrel combination improved biochemical androgenicity markers and moderate acne versus placebo — so a therapeutic effect is not implausible for the combination pill, likely driven by the estrogen component and SHBG elevation rather than by levonorgestrel’s own androgen profile. Overall, the mechanistic case for levonorgestrel specifically (as opposed to combined oral contraceptives generally, or lower-androgenicity progestins specifically) is weak and partly contradicted by the same evidence base.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT00480532	NA	Completed	131	Continuous oral contraceptive + doxycycline for bleeding control; acne mentioned only as background context for doxycycline use, not a levonorgestrel-acne efficacy trial (relevance grade B).
NCT05570786	Phase 2	Completed	100	Subdermal gestrinone implant for endometriosis-related pelvic pain; different drug (gestrinone) and indication — not directly applicable (relevance grade C).
NCT00161226	N/A	Terminated	44	Levonorgestrel IUS for prevention of endometrial cancer; acne mentioned only as a known side effect of oral progestins in general, unrelated to acne treatment (relevance grade C).
NCT05492487	Phase 2	Unknown	60	Fertility-sparing treatment of atypical endometrial hyperplasia (Mirena vs. megestrol); not related to acne (relevance grade C).
NCT01650168	N/A	Completed	101,498	Large safety cohort comparing nomegestrol acetate/estradiol vs. levonorgestrel-containing combined oral contraceptives; general safety data, not an acne efficacy trial (relevance grade C).

None of the retrieved trials directly test levonorgestrel (alone or in combination) as a treatment for acne as a primary endpoint.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
12196750	2002	RCT	Journal of the American Academy of Dermatology	Low-dose ethinyl estradiol/levonorgestrel (20mcg/100mcg) RCT showed improvement in moderate acne and androgenicity markers vs. placebo — the only direct positive evidence.
15025547	2004	Review	Drugs	Ethinylestradiol/chlormadinone acetate was significantly more effective than ethinylestradiol/levonorgestrel for mild-to-moderate papulopustular acne — evidence against levonorgestrel specifically.
6084924	1984	Study	Acta Dermato-Venereologica	Compared testosterone/SHBG changes in acne patients on desogestrel- vs. levonorgestrel-containing oral contraceptives; direct levonorgestrel-acne biochemical data.
7825629	1995	Review	The American Journal of Medicine	Explains why levonorgestrel is classed among the more androgenic progestins, underpinning the mechanistic caution above.
21895044	2011	Review	American Journal of Clinical Dermatology	Describes dermatological (anti-acne) benefits of a low-androgenicity progestin (chlormadinone), by contrast with levonorgestrel.
16796485	2006	Review	Journal of Women’s Health	Notes levonorgestrel (vs. drospirenone) is associated with acne vulgaris and hirsutism rather than their reduction.

Australia Market Information

No ARTG entries are present in this evidence pack (0 licences on record). Given levonorgestrel is a long-established, widely used progestin, this most likely reflects a gap in the regulatory data pull for this candidate rather than genuine unavailability — recommend a direct ARTG search to confirm before relying on this field.

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information. Key warnings, contraindications, and drug interaction data were not available in this evidence pack (flagged as a Blocking-severity data gap), so no safety-related claims can be made from this pack alone.

Conclusion and Next Steps

Decision: Hold

Rationale: The mechanistic case is weak and partly contradicted by the pack’s own evidence — levonorgestrel’s androgenic profile runs counter to the anti-androgenic mechanism typically needed for acne treatment, and a head-to-head comparison (PMID 15025547) found it inferior to a low-androgenicity progestin for this exact indication. No trial tests levonorgestrel directly against acne as a primary endpoint, and TFDA/TGA product-label safety data are entirely missing (Blocking gap).

To proceed, the following is needed:

TGA-approved Product Information / label warnings and contraindications
Confirmed mechanism of action data from DrugBank
Independent verification of Australian ARTG marketing status (0 entries in this pack is unexpected for a long-marketed molecule)
A trial or study directly comparing levonorgestrel-containing regimens against acne outcomes, ideally isolating levonorgestrel’s contribution from the estrogen component
Disclaimer

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