White Paper - Minoxidil (Rogaine)
Minoxidil (Rogaine) was the first agent to show hair regrowth. It is a piperidinopyrimidine derivative that is used orally as a blood-pressure lowering medication. With a large incidence of hypertrichosis (>80%) in individuals taking the oral form of minoxidil, a topical solution was developed for hair loss. At this time, the precise mechanism by which minoxidil works is not entirely established. However, it does not appear to act hormonally.
Minoxidil increases the duration of anagen and can reverse miniaturized hairs. It has been shown to have a direct mitogenic effect on epidermal cells with an increased survival time of keratinocytes in vitro. Minoxidil is a potassium channel agonist, which opposes the entry of calcium into the cells, which could in turn decrease epidermal growth factor and increase hair growth (calcium has the opposite effects).
Minoxidil Clinical Trials
In a hair weight study, both 2% and 5% solutions were found to be statistically significantly more effective than placebo with 35% increase in hair weight with the 5% solution and 25% with the 2% solution. The major increase in hair weights was observed in the first 20 weeks of therapy. However, minoxidil stopped hair loss for the 96-week treatment period compared with placebo. Stopping minoxidil will result in loss of hair weight over 6 months back to placebo-treated level. In women, a study that spanned 32 weeks found that the 2% solution increased hair weights by 42.5% compared with 1.9% in the placebo control.
Minoxidil can be used for both frontal and vertex thinning. It principally works to convert vellus hairs back into terminal hairs rather than by stimulating de novo hair growth. Most hair increases occur in the first 4 months but efficacy should be evaluated only after a year of therapy.
In a multi-center, double-blind study with 2294 men between the ages of 18 and 50, 30 to 35% applying 2% topical twice daily showed moderate to dense regrowth by hair counts and photographic analysis. In a multi-center, double-blind, placebo-controlled study of 256 women between the ages of 18 and 45 with androgenetic alopecia, 63% who applied 2% topical minoxidil twice daily showed minimal to moderate regrowth using hair count analysis.
Minoxidil was approved for men by the FDA as a 2% solution in 1988 and as a 5% solution in 1997. For women, the 2% solution was approved in 1991. Although the 5% solution is not approved for women, it has been used in women with success but with a higher incidence of secondary unwanted hair growth, which is reversible upon stopping. Both solutions are available over the counter and do not require a physician prescription in the United States. Topical minoxidil is recommended as a twice daily treatment protocol that must be applied directly to the scalp and not the hair.
Minoxidil Side Effects
Minoxidil is poorly absorbed on intact skin with only 0.3 to 4.5% reaching the systemic circulation with elimination entirely within 4 days if absorbed. It is metabolized by the liver and excreted in the urine. Studies have not shown any blood pressure fluctuations with topical minoxidil, but topical minoxidil still should be used with caution in individuals with cardiovascular problems. Minoxidil also should not be used in pregnant or nursing women. There have been no teratogenic effects reported in rats, but human data is lacking. Minoxidil is also secreted in human milk.
The most frequent side effect is an irritant contact dermatitis, most likely from the propylene glycol. The new 5% foam by the brand Rogaine has eliminated the propylene glycol ingredient and therefore may have a lower incidence of contact dermatitis. Scalp irritation has been noted to be about 7% with the 2% solution and may be slightly higher with the 5% concentration.
Facial hypertrichosis may occur in 3 to 5% of women with the greatest effect on the forehead, cheeks, and sides of the face. There is no clear evidence of how the hypertrichosis develops, i.e., whether through indirect skin contact or systemic absorption. Hypertrichosis is entirely reversible with cessation of minoxidil. Also, affected individuals have shown disappearance of facial hair within a year.