A clear understanding of the mechanism of Minoxidil’s action in the treatment of androgenetic alopecia can help develop more effective treatments for hair loss disorders as well as give a clearer insight into the biology of hair growth. Histological studies in primates showed that treatment with Minoxidil causes an increase in the proportion of follicles in anagen, a reduction in telogen follicles, and an increase in hair follicle size. In male pattern hair loss, the evidence available so far suggests that Minoxidil primarily acts on the hair cycle; though it is possible it may also increase hair diameter.
Minoxidil as a treatment drug in male androgenetic alopecia does not appear to have either a hormonal or immunosuppressant effect. Both in vitro and in vivo studies show that it has a direct mitogenic effect on epidermal cells; plucked anagen hair bulbs from men applying Minoxidil show a significant increase in proliferation index when cells were counted and measured by a flow cytometer.
Two percent topical Minoxidil (Rogaine) was U.S. Food and Drug Administration FDA – approved as a prescription product in 1988 and as an over-the-counter product in 1996. 5% percent topical Minoxidil, Rogaine Extra Strength, was subsequently approved for direct over-the counter use in 1998.
Clinical trials of topical Minoxidil in male pattern hair loss all show a remarkably rapid increase in hair growth, measured by hair counts or hair weight. This increase is apparent within 6–8 weeks of starting treatment and generally peaks by 12–16 weeks. This rapid hair growth cannot be attributed to the reversal of the follicular miniaturization process. It seems more likely that Minoxidil triggers follicles in the latent part of telogen (resting state) into anagen (growth phase).
Clinical trials of the efficacy of topical Minoxidil in men
The efficacy of topical Minoxidil in the treatment of androgenetic alopecia is undisputed in clinical trials in both men and women, but the results of histological studies in humans are less conclusive than those conducted in animals.
- Initial studies were performed in 2294 men with Hamilton patterns III (cosmetically significant amount of frontal hair loss) to VI male pattern baldness (significant frontal and vertex hair loss) by Olsen and colleagues. The patients were between the ages of 18 and 50, and were randomized to 1 ml of 2% or 3% topical Minoxidil vs. placebo twice daily for 4 months, and then the placebo group was changed over to active drug. Terminal and vellus hair counts were done directly in the target areas in the mid-vertex region, which was the area of greatest hair loss. Although hair re-growth with topical Minoxidil was not visible until almost 4 to 6 months of continuous use, Olsen and colleagues showed that the mean target area of terminal hair counts of subjects treated with 2% topical Minoxidil had increased.
- Two randomized, double-blind, placebo-controlled studies have evaluated the efficacy of 5% Minoxidil topical solution as opposed to 2% Minoxidil topical solution. For men in the age group 18 to 49 years with mild to moderate vertex hair loss, the 5% concentration has been found to be more effective. After 48 weeks of twice-daily treatment with 5% Minoxidil, a mean of 57% of 139 patients had re-growth, compared with 41% of 142 patients and 23% of 71 patients in the 2% Minoxidil and placebo-treated groups, respectively. The quality of re-growth was evaluated as mild to moderate in most individuals, but those using the 5% formulation showed greater improvement. Hair counts and patient rating of scalp coverage and treatment benefit were also observed to be appreciably better with the higher strength formulation. Peak hair counts occurred at 16 weeks with both concentrations.
- In a smaller study on 36 men aged 18 to 40 years who had mild to moderate fronto-parietal hair loss, a trend toward greater improvement was seen with the 5% dose based on hair weights, but this result was not statistically significant . After 96 weeks of treatment with 5% minoxidil, target-area hair weights increased by 35%, compared with an increase of 25% with 2% minoxidil. Untreated and placebo-controlled groups lost 6% in hair weight per year.
- Price et al evaluated four groups of nine men each with androgenetic alopecia over 120 weeks. Three groups applied either 2% or 5% topical Minoxidil solution or vehicle. The fourth group, unblinded, received no treatment. It was documented that subjects on 5% topical Minoxidil had a faster response in terms of increased hair weight and number than those patients on 2% topical Minoxidil, but both groups had a similar percentage increase in growth at 96 weeks. Discontinuation of 2% topical Minoxidil led to loss of whatever hair was gained over 3 to 4 months in both active groups, indicating that Minoxidil must be in continuous use to be effective.
- A large-scale 1-year observational study on patients who used 2% or 5% topical minoxidil showed no increased risk of cardiovascular events compared with controls.
Clinical use in male pattern hair loss
No drug has been so far found that completely prevents further loss of hair in male pattern hair loss. However, long-term (5-year) use of Rogaine twice daily has shown positive results. Even though there is increased shedding over the first several months of treatment as anagen is induced and telogen hairs are shed, hair counts remained substantially above baseline. Less frequent than twice daily application of the 2% topical Minoxidil leads to a lesser response.
Other than oral finasteride (Propecia) topical minoxidil (Rogaine) is the only treatments for male pattern hair loss that has been approved by the US Food and Drug Administration. The use of this drug is indicated in men older than 18 years with mild to moderate male pattern hair loss. Early intervention, when thinning is first perceived and hairs are not completely miniaturized increases the chances of success. Slowing down rate of hair loss, stabilization, and increased scalp coverage can be expected by 3 to 6 months of treatment, and are clearly evident by 1 year. However, the drug does not result in dense re-growth, nor can it grow hair in areas that are totally bald.