Low-dose oral minoxidil initiation for patients with hair loss an international modified Delphi consensus statement

Hair loss significantly impacts patients’ quality of life, and it may be nonscarring or scarring. Etiologically, hair loss may be hereditary (androgenetic alopecia [AGA]); related to age; congenital (hair shaft disorders); traction induced; inflammatory (primary scarring alopecia); autoimmune (alopecia areata); or secondary to medical, surgical, or emotional stressors (telogen effluvium), infection (tinea capitis), and certain medica- tions including cancer therapies.

Topical minoxidil is approved by the US Food and Drug Admin- istration (FDA) as an over-the-counter drug designed to treat male pa- tients with AGA (minoxidil, 5% solution, or minoxidil, 5% foam, twice daily) and female patients with AGA (minoxidil, 2% solution, twice daily, or minoxidil, 5% foam, once daily).2,3 It is also frequently prescribed off-label for other types of hair loss in children and adults.2-6 Common adverse effects include transient shedding with initiation, hypertrichosis, and contact dermatitis, most commonly secondary to nonactive formulary ingredients, such as propylene glycol.2

Minoxidil, a potent peripheral vasodilator, was originally ap- proved by the FDA in 1979 as an oral agent for patients with severe refractory hypertension with antihypertensive dosing ranging from 10 mg to 40 mg daily.6,7 Interestingly, a significant adverse effect of oral minoxidil was hypertrichosis, leading to the development of topical minoxidil as a hair growth agent in the 1980s.

Minoxidil exerts its effects via various proposed pathways: (1) a vasodilator acting on adenosine triphosphate–sensitive potassium channels, (2) an anti-inflammatory agent, (3) inducer of the Wnt/β- catenin signaling pathway, (3) a 5-α reductase inhibitor and antiandro- gen, and (4) an anagen extender.6 Topical minoxidil is converted into its active form, minoxidil sulfate, via sulfotransferase enzyme activity in the outer root sheath of hair follicles, and oral minoxidil is absorbed in the gastrointestinal tract and converted to its activated sulfated form in the liver.6 The systemic absorption of topical minoxidil is negligible, well below the minimum level of 20.0 ng per millimeter, at which hemodynamic changes in blood pressure have been documented.2 Oral minoxidil reaches peak levels in plasma within an hour, has a half-life of 3 to 4 hours, and is excreted by the kidneys within 12 to 20 hours.6

Oral minoxidil is not a first-line antihypertensive agent due to the risk for fluid retention, tachycardia, and other potential adverse effects, such as pericardial and pleural effusion, cardiac tamponade, and angina pectoris, with antihypertensive dosing.7 However, a grow- ing number of research groups have reported on the off-label use of low-dose oral minoxidil (LDOM), ranging from 0.25 mg to 5 mg daily, as a safe and effective treatment option for male and female pa- tients with AGA, age-related patterned thinning, traction alopecia, alopecia areata, telogen effluvium, scarring, and other forms of hair loss,4,5,8-22 though some serious adverse effects have been reported.23,24 This correlates with an increased demand for LDOM pre- scriptions in recent years.16 As the current data on LDOM initiation and monitoring for hair loss are limited, there is a pressing need for an ex- pert consensus–based statement for common use to maximize hair growth and minimize cardiovascular and other adverse effects.

Dermatologists with hair loss expertise, identified by clinical ex- perience, research activities, and participation in recognized pro- fessional societies, including the North American Hair Research Society, International Federation of Hair Research Societies, and World Congress for Hair Research, were invited via email to join the LOMI expert panel and engage in multiple survey rounds address- ing LDOM safety, efficacy, dosing, and monitoring for treating pa- tients with hair loss. Experts were encouraged to answer items based on their clinical expertise and experience with LDOM; relevant lit- erature was provided for review. To minimize bias, individual ex- pert responses were anonymous from all except the study coordi- nator (Y.M.A.). Based on consensus parameters set by prior Delphi studies, consensus for a LOMI item was defined as at least 70% of experts indicating agree or strongly agree on a 5-point Likert scale.28-34

The initial survey round included items that were non–Likert scale (demographic, open-ended, or multiple choice), as well as items requiring a Likert scale response (strongly disagree, disagree, neu- tral, agree, strongly agree; Figure). After each round, aggregated re- sponses were reviewed by the multidisciplinary LOMI steering com- mittee, and feedback was provided to the LOMI expert panel. When indicated, survey items were revised for clarification or to incorpo- rate expert comments and submitted for expert review in subse- quent rounds. In rounds 2, 3, and 4, survey items were calibrated ation, or did not achieve at least 70% consensus, were either re- vised or reconsidered in subsequent rounds or eliminated.