MINOXIDIL with RETINOIC ACID

As early as 1986 topical all-trans-retinoic acid (aka tretinoin or retinoic acid or Retin-A ® (marchio registrato) alone and in combination with minoxidil has been tested for the promotion of hair growth in patients with male pattern baldness (1). In the scholarly article in the Journal of the American Academy of Dermatology, there are cited several cases in which the use of retinoic acid alone prompted striking hair growth. A 43 year old woman, who had extensive androgenetic alopecia since age 20, experienced a 1100% increase in hair counts over an 18 month period. A male patient had previously received a series of hair transplants, but discontinued that treatment because of poor hair growth in the transplanted plugs. During the course of his treatment with retinoic acid, growth was initiated in the transplanted grafts and regular hair trimming was required. Overall, in subjects receiving retinoic acid in combination with minoxidil, positive responses were documented in 66%, with 44% placed in the good response group and 22% in the moderate response group. The five patients receiving placebo demonstrated no significant hair growth response. With the initital use of retinoic acid on the scalp, few patients experience an apparent increase in hair loss. The hair loss is more apparent than real and the same hair shaft replaces itself. But because the retinoic acid decreases the chemical bonding between the skin cells, hair that is in the telogen (resting) phase comes out more readily. (It would have come out anyway). It will also replace itself more readily and presumably with a hair shaft of greater thickness. There are postulated to be two mechanisms by which retinoic acid promotes hair growth in combination with minoxidil. Experimental evidence suggests that retinoic acid itself may play a significant role in hair growth (3) and, because retinoic acid has been shown to increase percutaneous absorption (4,5), it is possible that the increased absorption caused by retinoic acid may have a positive effect on the amount of minoxidil reaching the hair follicle cells. For the treatment of male pattern baldness, it is recommended that a 2% to 5% minoxidil topical solution be applied to the affected area twice a day. During the daytime, 1 ml of the 2% to 5% minoxidil solution alone should be applied. The nighttime application should contain 2% to 5% minoxidil with 0.025% retinoic acid. The proprietary preparation is commonly known as Retin-A ® (marchio registrato), manufactured by Ortho Pharmaceutical Pure retinoic acid is intensely yellow, so that unadulterated compounds of retinoic acid will have a yellowish cast. Retinoic acid has been used for more than 25 years in the treatment of acne. More recently, retinoic acid has been highly touted to reverse the aging of the skin, primarily due to solar exposure. In fact, U-V light is considered to be the chief contributing factor to aging skin. Therefore, unnecessary exposure to the sun is discouraged while using retinoic acid. Basically, the retinoic acid acts like a chemical peel. Erythema (redness), flaking, peeling and mild irritation frequently occurs with the use of retinoic acid, but is usually mild and limited to 7-10 days. As with minoxidil, the effects of retinoic acid on the skin are dose related. True contact allergy to topical retinoic acid is rarely encountered (2). The reaction in the skin is to induce protein synthesis as well as to increase cell turnover. Since retinoic acid is decomposed by strong light, it should only be applied at night.

(1)Bazzano GS, Terezakis N, and Galen W: Topical tretinoin for hair

growth promotion. J Am Acad Dermatol 15:880-883, 1986

(2)Nordquist BC, Mehn K: Allergic contact dermatitis to retinoic acid.

(3)Bazzano et al Contact Dermatitis 3:55-56, 1977

(4)Zbinden G: Pharmacology if vitamin A acid (13-cis, all-trans- retinoic acid). Acta Derm Venereol (Stockh) 55:21-24, 1975

(5)Ferry JJ, Forbes KK, LanderLugt JT and Szpunar GJ: Influence of tretinoin on the percutaneous absorption of minoxidil from an aqueous topical solution. Clin Pharmacol Ther 47:439-46, 1990

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