# Expanding the therapeutic landscape of minoxidil for androgenetic alopecia: topical, oral and sublingual formulations

**Authors:** Flavia Rodrigues Dias, Shin Shen Yong, Holly FitzGerald, Rodney D. Sinclair, Bevin Bhoyrul

PMC · DOI: 10.3389/fphar.2025.1718208 · Frontiers in Pharmacology · 2026-01-21

## TL;DR

This paper reviews different ways to use minoxidil for hair loss, including topical, oral, and sublingual forms, and discusses their effectiveness and safety.

## Contribution

The paper introduces sublingual minoxidil as a novel delivery method and evaluates its potential benefits over existing formulations.

## Key findings

- Topical 5% minoxidil consistently increases hair counts but results vary due to individual differences.
- Low-dose oral minoxidil is effective for patients unresponsive to topical therapy with minimal cardiovascular risks.
- Sublingual minoxidil may improve follicular bioavailability and reduce systemic side effects compared to oral use.

## Abstract

Androgenetic alopecia (AGA) is the most common form of non-scarring alopecia, affecting up to 80% of men and 50% of women by the age of 70. Minoxidil, initially developed as an oral antihypertensive, has become one of the most widely used therapies for AGA due to its safety and efficacy. This review presents an overview of current evidence on topical, oral and sublingual minoxidil. Topical minoxidil, the only FDA-approved treatment for AGA in both men and women, promotes hair growth through several proposed mechanisms described in the article. Randomised controlled trials show that 5% formulations consistently increase hair counts, although results vary due to differences in follicular sulfotransferase activity. Low-dose oral minoxidil (0.25–5 mg) has emerged as a practical option for patients unresponsive to topical therapy. Hypertrichosis is the most frequent adverse effect, while cardiovascular events are uncommon at low doses. Sublingual administration, a novel delivery route that bypasses first-pass metabolism, may enhance follicular bioavailability while limiting systemic exposure. Early evidence indicates similar efficacy to oral therapy, with a potentially lower risk of cardiovascular effects. Overall, topical minoxidil remains first line, while oral and sublingual formulations expand therapeutic options and support individualised management. Further large-scale, long-term studies are needed to define optimal dosing, confirm safety and determine whether sublingual administration offers consistent advantages over oral use.

## Linked entities

- **Chemicals:** minoxidil (PubChem CID 4201)
- **Diseases:** androgenetic alopecia (MONDO:0005339)

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, SULT1A1 (sulfotransferase family 1A member 1) [NCBI Gene 6817] {aka HAST1/HAST2, P-PST, P-PST 1, PST, ST1A1, ST1A3}, SULT2A1 (sulfotransferase family 2A member 1) [NCBI Gene 6822] {aka DHEA-ST, DHEA-ST8, DHEAS, HST, ST2, ST2A1}, ABCC9 (ATP binding cassette subfamily C member 9) [NCBI Gene 10060] {aka ABC37, ATFB12, CANTU, CMD1O, IDMYS, SUR2}, BCL2A1 (BCL2 related protein A1) [NCBI Gene 597] {aka ACC-1, ACC-2, ACC1, ACC2, BCL2L5, BFL1}, EDA2R (ectodysplasin A2 receptor) [NCBI Gene 60401] {aka EDA-A2R, EDAA2R, TNFRSF27, XEDAR}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, PTGS1 (prostaglandin-endoperoxide synthase 1) [NCBI Gene 5742] {aka COX1, COX3, PCOX1, PES-1, PGG/HS, PGHS-1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}
- **Diseases:** itching (MESH:D011537), pericardial effusion (MESH:D010490), autosomal dominant disorder (MESH:D030342), Hypotension (MESH:D007022), Cantu syndrome (MESH:C535572), scarring alopecia (MESH:D002921), impaired self-esteem (MESH:D012652), stroke (MESH:D020521), weight gain (MESH:D015430), pleural effusions (MESH:D010996), facial anomalies (MESH:C557821), reflex tachycardia (MESH:D013610), arrhythmia (MESH:D001145), AGA (MESH:D000505), anxiety (MESH:D001007), congenital (MESH:D008209), fluid (MESH:D002559), lower limb oedema (MESH:D038061), circulatory shock (MESH:D012769), syncope (MESH:D013575), Fluid overload (MESH:D019190), loss (MESH:D016388), fibrosis (MESH:D005355), unstable angina (MESH:D000789), alopecia areata (MESH:D000506), drug overdose (MESH:D062787), peripheral oedema (MESH:D010523), contact dermatitis (MESH:D003877), cardiomegaly (MESH:D006332), palpitations (MESH:D006331), allergy (MESH:D004342), pulmonary fibrosis (MESH:D011658), LDOM (MESH:D009800), Hypertrichosis (MESH:D006983), depressive symptoms (MESH:D003866), Scalp irritation (MESH:D004476), cardiovascular side effects (MESH:D064420), HF (MESH:D006201), dizziness (MESH:D004244), Cardiovascular adverse effects (MESH:D002318), myocardial infarction (MESH:D009203), oedema (MESH:C536897), vascular remodelling (MESH:D066253), orthostatic hypotension (MESH:D007024), hypertension (MESH:D006973), facial flushing (MESH:D005483)
- **Chemicals:** PGF2alpha (MESH:D015237), ethanol (MESH:D000431), PGD2 (MESH:D015230), norepinephrine (MESH:D009638), bleomycin (MESH:D001761), arachidonic acid (MESH:D016718), butylated hydroxytoluene (MESH:D002084), pinacidil (MESH:D020110), PGE2 (MESH:D015232), phenylephrine (MESH:D010656), Prostaglandin (MESH:D011453), prostaglandin endoperoxide (MESH:D011449), oxygen (MESH:D010100), bicalutamide (MESH:C053541), stearyl alcohol (MESH:C009316), dopamine (MESH:D004298), nicorandil (MESH:D020108), DHT (MESH:D013196), diazoxide (MESH:D003981), alcohol (MESH:D000438), cysteine (MESH:D003545), lipid (MESH:D008055), dutasteride (MESH:D000068538), Minoxidil (MESH:D008914), midodrine (MESH:D008879), spironolactone (MESH:D013148), propylene glycol (MESH:D019946), cetyl alcohol (MESH:C005031), thymidine (MESH:D013936), potassium (MESH:D011188), finasteride (MESH:D018120), 2,6-diamino-4-piperidinopyrimidine-1-oxide (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** HF — Homo sapiens (Human), Hairy cell leukemia, Cancer cell line (CVCL_B401), DPC — Canis lupus familiaris (Dog), Canine prostate carcinoma, Cancer cell line (CVCL_DN59)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12898826/full.md

## References

96 references — full list in the complete paper: https://tomesphere.com/paper/PMC12898826/full.md

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Source: https://tomesphere.com/paper/PMC12898826