Oral Minoxidil for Hair Loss: Update and Perspectives

Abstract

BACKGROUND Minoxidil was first introduced in the 1970s as a treatment for refractory hypertension.1 Due to its side-effect profile, its use is reserved for hypertension that has not responded to conventional multidrug regimens.1,2 Tachycardia, fluid retention, and generalized hypertrichosis are minoxidil’s most common adverse effects.2 It was first noted to improve hair loss in male androgenetic alopecia in 1980.3 These observations led to the development of topical minoxidil (TM) as a hair growth agent. It was approved by the United States Food and Drug Administration as a topical treatment for androgenetic alopecia (AGA) in men in 1988 and in women in 1992.4 For several decades, TM has been utilized for AGA. Clinical trials have demonstrated its safety and efficacy in both women and men; however, the clinical response has been variable, and around 50% of patients do not experience any clinical benefit.5,6 Minoxidil is a pro-drug and requires conversion to minoxidil sulfate by the sulfotransferase enzymes to be biologically active.7 Sulfotransferases are xenobiotic metabolizing enzymes expressed in many tissues; when minoxidil is applied to the hair on the scalp, it must be converted by the sulfotransferase present in the hair follicle outer root sheath (ORS).7 The sulfotransferase activity varies among individuals, and a positive association between its activity in the ORS and the clinical response to TM has been found.6,8 However, a lower activity threshold is required to bioactivate oral minoxidil compared with TM.9 This could be because of the liver sulfotransferase’s extensive metabolization of oral minoxidil. As a chronic condition, AGA demands continuous treatment.10 Unfortunately, many patients are poorly compliant with topical therapy due to the resultant undesirable hair texture, scalp irritation, or even the time-consuming nature of having to apply TM repeatedly.11 The usual daily dose of oral minoxidil for hypertension ranges from 10-40 mg/day, and it was not used for alopecia for decades because of its dose-related adverse effects. The use of low-dose oral minoxidil (LDOM; 0.25-5mg/day) for AGA aims to avoid the issues associated with topical application, improve compliance, and enhance clinical response.12 LDOM has been increasingly used for the treatment of AGA. Since Prof. Sinclair’s seminal study, several articles have been published. However, available data is still limited and results mainly from low-evidence studies. Prof. Sinclair evaluated 100 women treated with 0.25mg of minoxidil combined with 25mg of spironolactone for 1 year. He observed a mean reduction in the hair loss clinical scale (ranges from 1 to 5) of 1.3 after 12 months.13