Should Oral Minoxidil be Our First Choice for Treatment of Alopecia?

ABSTRACT

Low-dose oral minoxidil has gained popularity as an off-label pharmacological treatment of hair loss with an alleged high safety profile. Since the original introduction of low-dose oral minoxidil for treatment of pattern hair loss by Sinclair, reported adverse effects (AEs) have been purported to be infrequent and of a minor impact, and some experts have suggested minoxidil as first line agent for treatment of alopecia. Nevertheless, as such it should be prescribed with caution and be monitored by physicians experienced and aware of the AEs of the drug and potential medicolegal issues due to its status as off label medication. Observations into the genetic basis of Cantú syndrome have identified the condition as a potassium channelopathy, corroborating the role of the sulfonylurea receptor that forms ATP-sensitive potassium channels for the hair growth promoting effect of minoxidil sulfate. The phenotype of Cantú syndrome involves a generalized terminal hair hypertrichosis, acromegaloid features, and cardiopathy including pericardial effusion. It may be inferred that the potential AEs of minoxidil represent a dose-dependent phenotypic mimicry of Cantú syndrome with interindividual variability in susceptibility, and are not idiosyncratic as formerly proposed. Indeed, besides hypertrichosis, oral minoxidil has been observed to cause pseudoacromegaly with high dose, and pericardial effusion even with low dose. Some experts advocate prescription of additional drugs to counteract the AEs of oral minoxidil. Particularly, spironolactone has found favor as a diuretic with antiandrogen activity, and more recently bicalutamide has been proposed to improve minoxidil-induced hypertrichosis in female pattern hair loss, however, minoxidil-induced hypertrichosis is by definition not androgen dependent, and bicalutamide is pregnancy category X in the USA, and pregnancy category D in Australia. Ultimately, the risk of adverse drug-related events increases with polypharmacy, especially in women and the elderly. Finally, oral minoxidil is contraindicated during pregnancy and lactation for reasons of teratogenicity and the possibility of hypertrichosis in the breastfed infant.