Topical Minoxidil : Effectiveness & Limitations
Available topical formulations
Minoxidil is offered in 2% and 5% concentrations, applied to the scalp as a liquid or foam. Both concentrations are FDA approved for men and women. All topical forms are sold over-the-counter (OTC) and do not require a prescription. Many expensive “hair growth therapies” actually rely on topical minoxidil combined with other ingredients that are not FDA approved as hair loss treatments.
The foam preparation does not use propylene glycol as a solvent. Propylene glycol has a greasy feeling and is a common skin irritant, which makes the foam an attractive alternative to the solution for some patients. At present, the foam preparations are a 5% concentration- for both men and women.
Minoxidil is offered in 2% and 5% concentrations, applied to the scalp as a liquid or foam.. Both concentrations are FDA approved for men and women. All topical forms are sold over-the-counter (OTC) and do not require a doctors prescription. Many expensive “hair growth therapies” actually rely on topical minoxidil combined with other ingredients that are not FDA approved as hair loss treatments.
The foam preparation does not use propylene glycol as a solvent. Propylene glycol has a greasy feeling and is a common skin irritant, which makes the foam an attractive alternative to the solution for some patients. At present the foam preparations are a 5% concentration- for both men and women.
Topical: applied to the scalp as a liquid or foam, ideally right after bathing so it is not washed away. Maximum efficacy requires application 2 times daily to the affected area for men; 1 time daily for women. The original minoxidil study results used to gain FDA approval were only performed on the vertex area, so they were only approved for this claim. However, minoxidil can stimulate hair growth wherever the active medication can reach. Most hair restoration doctors advise patients to use minoxidil on all thinning areas, both the vertex and frontal scalp. However, patients must be consistent and apply this therapy daily or risk causing shedding. If patients decide to discontinue topical minoxidil it is advisable to wean the dosing over several weeks rather than abrupt discontinuation, as the latter is more likely to provoke shedding in patients who are responders.
Oral minoxidil: Some doctors around the world are beginning to use low dose minoxidil orally (5mg or less per day) combined with spirinolactone with reported success.(8) Patients irritated by minoxidil topically usually do well with the oral route. This also allows physiologic activation of the drug to occur internally, which likely increases the response rate. However, oral minoxidil has not been FDA approved for hair loss treatment. Off label users must take care to maintain low doses to avoid potentially serious systemic effects.
Mode of Action
How minoxidil acts to slow hair loss and stimulate hair regrowth is not well understood. It is believed that minoxidil sulfate acts by prolonging the anagen phase (growth phase) of the hair follicle, and increasing the size of the follicle. (9)
Studies have shown that minoxidil slows or halts hair loss and promotes hair regrowth in both men and women, at both 2% and 5% formulations. The 5% formulation is generally more effective. Positive response to minoxidil therapy (reduced hair loss and/or hair regrowth) has been reported in various studies as less than 50% to more than 80% –possibly owing to genetic variation in study recipients. Any positive response is lost if minoxidil therapy is discontinued.
The most common reported side effects are scalp redness, Itchy scalp, dryness and flaking. Accidental application of minoxidil to the face can result in growth of unwanted facial hair, and the risk of facial hair growth from absorption is about 3% in most studies. Repeated, large applications of minoxidil have been associated with a drop in blood pressure in a few reported cases, presumably due to systemic absorption. There are also infrequent reports of heart palpitations, which require discontinuation of use.
Some patients may develop a true allergy with associated swelling and hives. In these cases, minoxidil can’t be used. The older pregnancy classification is a C. Newer classifications recommend not using minoxidil during pregnancy, with at least one case report of possible teratogenicity, though a causal relationship with minoxidil has not been shown.
Minoxidil can stimulate all hair, and the topical formulation is currently the only drug approved for treatment of female pattern hair loss.
Minoxidil can be a valuable retardant to hair loss even in cases where it does not appear to regrow hair. Often patients discontinue minoxidil after several months if they haven’t noticed increased growth. However, for responders, the effect of retarding hair loss can be important compared to continued hair loss over the years. A patient who sheds after discontinuing this therapy is a likely responder, and may wish to reconsider resuming the medication if this occurs. Also, combined with oral finasteride, minoxidil appears to synergistically enhance hair regrowth effect of finasteride. Hair doctors commonly recommend the combination of these drugs, provided patients are committed to the daily regimen that topical minoxidil requires.
The discovery of minoxidil as a hair loss therapy was serendipitous, since it was first developed in the late 1960’s as an oral treatment for high blood pressure based on its function as a blood vessel dilator (vaso-dilator). However, it was quickly reported by some patients to have a side effect of hypertrichosis (hair growth stimulant) causing increased hair growth. This side effect lead researchers to formulate a topical solution for targeted treatment of scalp hair loss, in order to avoid the systemic effects on blood pressure and possible unwanted hair growth in other areas of the body. (1,2)
In 1988 the FDA approved 2% topical minoxidil as an effective treatment to combat hair loss caused by androgenetic alopecia (male pattern baldness) in men. The solution was known by the brand name, Rogaine. Then, in 1992, the FDA also approved its use in women for treatment of female pattern hair loss. Since then, further renditions of the topical solution have been created, including a 5% solution as well as a 5% foam.(3) Despite its impressive ability to stabilize and improve the appearance of hair density in some patients, the response to topical minoxidil therapy has not been universal, with variable response rates reported in the 50-80% range. Even though responders did better with higher concentrations of topical minoxidil , there were still some patients who did not respond at all. (4) Researchers determined that minoxidil is a ”pro-drug”, and in order to stimulate hair growth, it must undergo a chemical reaction in the body to produce the active ingredient minoxidil sulfate . The presence of the enzyme minoxidil sulfortransferase is key to this reaction. (5) All people have many types of sulfotransferase enzymes in various body tissues which function to attach a sulfate molecule when needed for various physiologic needs . At least one study has shown that varying levels of the sulfotransferase enzyme in human scalp correlate with the effectiveness of minoxidil as a hair growth stimulant. (6) The amount of the sulfotransferase enzymes appears to be under genetic control and it is postulated that genetic differences in sulfation capacity determine a patients response to minoxidil (7) Non-responders appear to have little available enzyme to convert the minoxidil into the active ingredient, minoxidil sulfate.
One may question why the therapy isn’t just administered in its active form to begin with. Unfortunately, outside of the body’s physiologic environment, minoxidil sulfate is highly unstable The only known mechanism for activation to safely occur, is by physiologic sulfation inside the body or inside the hair follicle during topical absorption.
1) Zappacosta AR. Reversal of baldness in patient receiving minoxidil for hypertension. New England Journal of Medicine 1980;303:1480.
2) Zins GR. The history of the development of minoxidil. Clinical Dermatology 1988;6:132–47.
3) Medical treatments for male and female pattern hair loss, Rogers, N.; Avram, M.; J Am Acad Dermatol, Vol 59, No 4, pp547-566, 2008
4) A multicenter, randomized, placebo-controlled, double blind clinical trial of a novel formulation of 5% minoxidil topical foam vs placebo in the treatment of androgenetic alopecia in men; Olsen, E.; Whiting, D.; Bergfeld, W.; Miller, J.; Hordinsky, M.; Wanwer, R.; Zhang, P.; Kohut, B.’ J Am Acad Derm, Nov., 767-774, 2007
5) Minoxidil Sulfate is the Active Metabolite that Stimulates Hair Follicles, Buhl, A.; Waldon, D.; Baker, C.; Johnson, G.; The Journal of Investigative Dermatology, pp553—557,1990
6) Minoxidil sulfotransferase activity influences the efficacy of Rogaine topical solution (TS): enzyme studies using scalp and platelets. Buhl, AE,; Baker, CA.; Dietz, AJ.; J Invest Dermatol, 1994; 102:534
7) Molecular Biology of the human cytosolic sulfotransferase gene superfamily implicated in the bioactivation of minoxidil and cholesterol in skin, Dooley, T.P.; Exp Derm, Aug 8(4); pp328-9, 1999
8) Female pattern hair loss: a pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone.
Sinclair RD, International Journal of Dermatol, 2018, Jan;57 (1): 104-108