Androgenetic alopecia
AGA is a non-scarring alopecia in which terminal hairs transform into miniaturized hairs. Typically in men, baldness occurs with frontal recession and vertex thinning,26 while in women, hair loss is characterized by a decrease in hair density over the crown without frontal hairline involvement, also known as female pattern hair loss (FPHL).27 Testosterone plays a role in AGA pathogenesis following conversion to dihydrotestosterone (DHT) by 5-alpha reductase.28,29
A meta-analysis showed that topical minoxidil at all concentrations provided superior results to those achieved in the placebo group. Regarding AGA, the study showed mean differences of 8.11 hairs/cm2 and 14.90 hairs/cm2 associated with the 2% and 5% minoxidil treatments, respectively, compared to the placebo group. While a comparison of the 2% minoxidil and placebo groups in female patients showed a mean difference of 12.41 hairs/cm2.30 A 5-year follow-up study in 31 AGA patients treated with 2% and 5% MS showed peak hair regrowth at 1 year.31
Numerous clinical trials were conducted with topical minoxidil at several concentrations in different preparations to test the efficacy of the formulation. In men with AGA, 5% MS demonstrated a significant increase in the mean difference in hair density compared with the 2% MS and placebo treatments.15,32,33 An earlier response was noted with 45% more hair regrowth in the 5% MS group than that in the 2% MS group at week 48. Both 2% and 5% MS showed promising results in FPHL. However, side effects such as dermatitis, headaches, and hypertrichosis were more common with 5% MS. Hypertrichosis could be problematic in women, leading to poor treatment compliance and, therefore, 2% MS is preferable.34 Interestingly, 1% MS proved to be effective in Asian women, with a significant increase in non-vellus hair compared to that in the placebo group.35 Evidence from randomized controlled trials of topical minoxidil in AGA and FPHL is summarized in Tables 2 and and3,3, respectively.
The higher occurrence of contact dermatitis with MS led to the development of PG-free foam formulations to treat hair loss. In AGA patients, 5% MF was well tolerated and superior to placebo. Only 5% of the patients experienced symptoms of scalp irritation after 52 weeks of treatment.32
For male AGA, the recommended treatment is twice daily application of 1 mL 5% MS and half a capful of 5% MF.38 The treatment advised for FPHL is twice daily application of 1 mL 2% MS and once daily application of half a capful of 5% MF. Once daily topical application of 5% MF has been proven to be as effective as twice daily application of 2% MS in FPHL with significantly fewer adverse events.36,37 Treatment should be continued indefinitely as termination of medication results in hair shedding within 3 to 4 months. Although there are limited data on teratogenicity, no serious adverse outcomes have been reported. As a safety measure, minoxidil should be avoided during pregnancy and lactation.39
The treatment response to topical minoxidil in AGA patients can be predicted by measuring sulfotransferase activity in plucked hair follicles. Studies have reported 93% sensitivity and 83% specificity.40 The enzymatic assay also demonstrated great accuracy by correctly detecting 94% of non-responders.41 A subsequent study using this assay showed that at the week 8 of topical minoxidil treatment, the sulfotransferase enzyme activity in hairs stabilized. This finding suggests that those who respond to minoxidil will not develop resistance to the existing dosage and, similarly, non-responsive patients will not turn into responders.42 A study by McCoy et al demonstrated that an increase in topical minoxidil concentration up to 15% in patients predicted to be non-responders increased the clinical response compared to that associated with 5% minoxidil without cardiac side effects.43 Therefore, the non-responders may have a clinical response with increased concentration of minoxidil.
There has been an increase in the use of a novel formula, minoxidil sulfate-based solution (MXS) since it is an active metabolite of minoxidil. It has been proven that MXS has a higher efficacy than that of the conventional formula and might be an option for patients with low minoxidil sulfotransferase activity.16,44 However, because of its larger molecular weight, which affects its penetrability, and its higher degree of degradation than that of MS, MXS may not be as efficacious.45 To improve response, MXS should be applied at higher concentrations and the formulation should be kept in small package to decrease the instability of the solution.44 A study conducted in 44 patients with AGA and FPHL who did not show improvements with twice daily application of 5% MS reported responsiveness to 10% MXS after treatment for 4 months. Side effects were tolerable irritation, erythema, and folliculitis.46 Therefore, we believe that MXS is a promising agent for those who are MS non-responders.
Attempts have been made to use oral minoxidil for AGA or FPHL patients who were not satisfied with conventional treatment. A combination of low-dose minoxidil 2.5 mg and spironolactone 25 mg in patients with FPHL showed preferable outcomes with decrease hair shedding and improved hair density. The mean severity score reduced to 2.3 at 6 months and 2.6 at 12 months. Mild adverse effects including urticaria, postural hypotension, and facial hypertrichosis were reported. No significant change in blood pressure was observed in the study.47
