Topical tretinoin for the treatment of pattern hair loss

Tretinoin essentially is a derivative of vitamin A. Topical tretinoin is used by dermatologists in the treatment of mild to moderate acne and on skin that has been damaged by excessive exposure to the sun. Two treatment forms of retinoic acid have been developed – all-trans-retinoic acid and 9-cis retinoic acid.

As a retinoid that regulates the growth and differentiation of epithelial cells, topical Tretinoin can be used to help enhance the effects on Minoxidil for the treatment of hair loss. Although Tretinoin alone does not act as a significant stimulant of hair growth, there is some evidence that a combination of Minoxidil (0.5%) and Tretinoin (0.025%) promotes hair growth in men with androgenetic alopecia. This is most likely due to the increased absorption of Minoxidil through alteration of the horny outer layer of the epidermis, the stratum cornum.

Mechanism of action

Tretinoin is a biologic response modifier. It is a potent cell mitogen that promotes and regulates epithelial cell growth and differentiation. It promotes angiogenesis (the formation of new blood vessels) and increases percutaneous absorption by affecting the fluidity and the lipid composition of cell membranes. In the treatment of androgenetic alopecia, Topical Tretinoin appears to increase the beneficial effects of Minoxidil in inducing hair re-growth by stimulating the growth of suboptimal hairs and could also act synergistically with Minoxidil to produce more dense hair re-growth than either compound can produce alone.

Efficacy and clinical trials

Animal research has shown that topical Tretinoin can induce hair growth in hairless retinol (vitamin A)-deficient gerbils or desert rats. Similar studies in mice found that only all-trans-retinoic acid and 9-cis retinoic acid are effective in inducing hair growth. Reports of the combined effect of topical Tretinoin and Minoxidil in humans are also available but require verification by larger controlled studies.

• A small study on men with androgenetic alopecia showed some hair re-growth when treated for 1 to 2 years with a combination solution of 0.025% Tretinoin and 0.5% Minoxidil formulated using generic powder forms.
• In one study of 36 men with male pattern baldness treated with a topical mixture of 0.025% Tretinoin and 0.5% Minoxidil mL twice daily for a mean of 8 to 10 months, 44 percent (16 of 36) of the subjects had a “good” (2:46 percent increase in target area hairs) response to therapy. This was compared with a “good” response in 2 of 12 (16 percent) subjects on 0.025% topical Tretinoin alone, none of 3 on placebo, and none of 3 on 0.5% topical Minoxidil alone.
• Ferry and colleagues found that absorption of 1mL of 2% topical Minoxidil almost tripled when Tretinoin 0.05% cream was co-administered once daily vs. 1.3-fold with placebo.
• Another study compared once-daily topical application of 0.05% Tretinoin and once daily 2% Minoxidil with twice-daily application of 2% topical Minoxidil solution in men with male pattern baldness. The combined use of the two drugs showed a slight, but not statistically significant, increase in effectiveness over the use of Minoxidil alone, and Minoxidil blood levels did increase with the concomitant use of Tretinoin.

However, the manufactured formulations of Tretinoin (Retin-A®) and Minoxidil (Rogaine®) are incompatible and become ineffective if compounded in one formulation. They must either be mixed using generic powder forms or be applied as separate treatments.

For efficacy, Rogaine® must be applied every morning and night and Retin-A® during the day. Even though there appears to be some benefit in using the combination, the need for an extra application during the day is generally considered to be rather inconvenient, discouraging wide acceptability. Additionally the skin irritation caused by Tretinoin is not always well tolerated.

Side effects

The potential side effects of topical Tretinoin are irritation and photosensitivity. As Tretinoin does not work alone, the potential side effects of Minoxidil should also be considered when administering treatment. Concerns about increased irritation, possible systemic absorption of drug, and difficulties related to the use of both agents together has led to the limited usage of this line of treatment.