Low-Dose Oral Minoxidil for Alopecia: A Comprehensive Review

Abstract

Low-dose oral minoxidil (LDOM) has demonstrated a promising safety and efficacy profile in the treatment of various hair disorders, including male androgenetic alopecia (AGA) and female-pattern hair loss (FPHL); however, it lacks FDA approval. The usual LDOM starting dose for male AGA is 1-5 mg/day, depending on physician preference and the patient's condition. For FPHL, it is 0.5-1 mg/day. The maximum dose is generally 5 mg/day. If patients respond well without major side effects, the dose may be gradually increased since the LDOM's efficacy appears to be dose-dependent. Patients may use LDOM long term if the treatment outcome is satisfactory. The common side effects of LDOM are hypertrichosis and cardiovascular symptoms. Females are more prone to hypertrichosis than males. The side effects of LDOM can be categorized as (a) dose-dependent type A side effects (hypertrichosis and cardiovascular symptoms) and (b) idiosyncratic type B side effects (pericardial effusion). Minoxidil acts via multiple pathways. Although minoxidil has a relatively short half-life of around 4 h, its hypotensive effect may last approximately 72 h. Effective treatments for alopecia are limited. Therefore, LDOM could be an important addition to the available therapies for managing some hair disorders, including AGA.

Keywords: Androgenetic alopecia; Female-pattern hair loss; Hair disorders; Minoxidil; Oral administration.

Fig. 1.

The proposed mechanism of action of minoxidil. Minoxidil stimulates the ATP-sensitive potassium channel, which eventually leads to vasodilation. Dilated blood vessels can carry more oxygen and nutrients to the hair follicles and thus promote hair growth. Minoxidil may also downregulate the expression of the interleukin-1 alpha gene, and thus may reduce perifollicular microinflammation by inhibiting inflammatory mediators such as interleukin-1 alpha, which facilitates hair growth. Minoxidil may inhibit the expression of 5 alpha-reductase type II gene and thus may act as an antiandrogen and promote hair growth. Minoxidil may also induce Wnt/b-catenin signaling pathway by stimulating the release of VEGF in the dermal papilla cell, leading to hair follicle regeneration. 5 AR-1, 5 alpha-reductase type I; 5 AR-2, 5 alpha-reductase type II; ARe, androgen receptor; β-cat, beta-catenin; Ca, calcium; DHT, dihydrotestosterone, IL-1α, interleukin-1 alpha; IL-1α gene, interleukin-1 alpha gene; K, potassium; NADP+, nicotinamide adenine dinucleotide phosphate; NADPH, reduced form of NADP+; O₂, oxygen; T, testosterone; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; Wnt, wingless-related integration site.

Fig. 2.

Pharmacokinetics of oral minoxidil.

Fig. 3.

Classification of side effects of LDOM.

Fig. 4.

Oral minoxidil-associated CVS symptoms and hypertrichosis seem to be dose-dependent. CVS symptoms included hypotension, edema, premature ventricular contractions, fatigue, tachycardia, and ECG changes. †The numerator indicates the patient number experiencing the side effect, and the denominator indicates the total number of participants in clinical studies.

Fig. 5.

a Distinction in side effects between oral and topical minoxidil. b Hypertrichosis is more prone in female oral minoxidil users.