Do higher concentrations of topical minoxidil work better?

Data mixed as to whether higher concentrations truly work better

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Minoxidil is a topical product that is approved by the FDA for treatment of androgenetic alopecia.

Minoxidil is not active when applied to the scalp. Minoxidil must be activated and such activation occurs by minoxidil sulfotransferase enzyme SULT1A! in the outer root sheath of suprabulbar hair follicles. It is well recognized that some patients have low hair follicle SULT1A1 activity and this is associated with a lower likelihood that minoxidil will prove helpful in promoting hair regrowth. According to 2020 data from Ramos et al, about 60 % of the population is thought to have low SULT1A1 activity.

5 % Minoxidil is better than 2 % Minoxidil in men

In 2002, Olsen et al showed clearly that 5 % minoxidil was superior to 2 % minoxidil

Are concentrations higher than 5 % better than 5 % ?

It has been proposed by some that higher concentrations of topical minoxidil might work better. There are many challenges however to using higher concentrations. First, concentrations higher than 5 % don’t always stay in solution and the product can precipitate out of solution leaving crystals in the bottle or a white powder on the scalp. Higher concentrations may also carry a greater chance to irritate and a greater chance to cause headaches and heart palpitations and dizziness.

Minoxidil is now available in different percentages ranging from 1 % to 30 %. Lotions, solutions, foams, gels are all widely available.

A new review by Singh et al. titled “Does topical minoxidil at concentrations higher than 5% provide additional clinical benefit?” was published in the November issue of Clinical and Experimental Dermatology and examines the studies of high dose topical minoxidil. The authors review three studies including one of their own (Goldust 2020)

McCoy J et al 2016

McCoy et al was one of the earliest studies examining benefits of high doses of minoxidil. This was a short 12 week study of women with AGA who did not respond to topical 5 % minoxidil. Patients were treated with 15 % minoxidil. 60 % of the patients responded to treatment. At the 12 week time point, 60% of subjects achieved a clinically significant response based on target area hair counts (increased 13.7% from baseline). There was also a significant improvement in global photographic assessment.

Goldust Study of 2020

The Goldust Study was a randomized, self-comparative clinical trial of 66 patients with AGA. The goals was to compare the safety and efficacy of twice daily minoxidil 15% solution with twice daily standard 5% solution when used over 24 weeks. Minoxidil 15 % worked better than 5 % at weeks 12 and 24 of the study. Side effects were similar and not statistically increased in the 15 % group.

Ghonemy S et al 2021

Ghonemy and colleagues conducted a 36 week randomized placebo-controlled, double-blind trial assessing minoxidil 5 %, minoxidil 10 % and placebo. At the end of the 36-week period, hair counts were higher in the 5 % group than the 10 % group and higher than placebo. Improvement in global photography seemed similar in the 5 % and 10 % groups. Side effects were higher in the 10 % group compared to the 5 % group and such side effects included initial hair shedding, contact dermatitis and hypertrichosis.

Conclusion

There are mixed views about whether higher minoxidil concentrations are truly better than standard 5 % concentrations. Data to date would suggest that it probably is, but it may come with a greater risk of side effects like irritation, shedding and hypertrichosis.

Overall, studies are small in size and short duration. Larger studies with global photography and patient and physician assessments will help answer the question: Is a higher concentration of minoxidil really worth it or not?

Some pharmacists tell me that minoxidil starts precipitating out of solution once you go beyond 7 -8 % so if propylene glycol is the solution then that’s probably the maximum. However if other vehicles are used, then the concentration is going to be higher. I have patients who come to see me on 15 % and 30 %. It seems to me that side effects are greater on higher concentrations (especially irritation and palpitations) but we lack good data to know if it works better.

Data to data hint that it just might.

MAIN REFERENCE

Singh et al. Does topical minoxidil at concentrations higher than 5% provide additional clinical benefit? Clin Exp Dermatol. 2022 Nov;47(11):1951-1955.

OTHER REFERENCES

Ramos PM, Sinclair R, Miot HA, Goren A. Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil treatment in Brazilian female pattern hair loss patients. Dermatol Ther 2020; 33: e13195.

Ramos PM, Gohad P, McCoy J et al. Minoxidil sulfotransferase enzyme (SULT1A1) genetic variants predicts response to oral minoxidil treatment for female pattern hair loss. J Eur Acad Dermatol Venereol 2021; 35: e24–6.

Olsen EA, Dunlap FE, Funicella T et al. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol 2002; 47: 377–85

Goldust M. Minoxidil 15% solution versus minoxidil 5%solution in the treatment of androgenetic alopecia. Br JDermatol 2020;183(Suppl): 91 (abstract BH107)

Ghonemy S, Alarawi A, Bessar H. Efficacy and safety of a new 10% topical minoxidil versus 5% topical minoxidil and placebo in the treatment of male androgeneticalopecia: a trichoscopic evaluation. J Dermatolog Treat 2021;32: 236–41

McCoy J, Goren A, Kovacevic M, Shapiro J. Minoxidil dose response study in female pattern hair loss patients determined to be non-responders to 5% topical minoxidil. J Biol Regul Homeost Agents 2016;30: 1153–5