Topical Tretinoin and Minoxidil
Tretinoin is a derivative of vitamin A; used by dermatologists in the treatment
of mild to moderate acne and in the treatment of skin that has been damaged
by excessive sun exposure. There are two treatment forms of retinoic acid
that have been developed; all-trans-retinoic acid and the 9-cis retinoic
Topical Tretinoin can be used to help enhance the effects of Minoxidil
in the treatment of hair loss because retinoic acid regulates the growth
and differentiation of epithelial cells. There is some evidence that Tretinoin
(0.025%) in combination with Minoxidil (0.5%) promotes hair growth in men
with pattern baldness, although Tretinoin alone does not act as a significant
hair growth stimulant. The alteration effect of Tretinoin to the horny outer
layer of the epidermis called the stratum cornum promotes absorption of
Minoxidil, thus enhancing its effects.
Role of the Topical Tretinoin
The action of Tretinoin is a biologic response modifier; potent cell mitogen
that promotes and regulates the growth and differentiation of the epithelial
cells. It also promotes the formation of new blood vessels – angiogenesis,
and increases percutaneous absorption by affecting the fluidity and the
lipid composition of cell membranes. Topical Tretinoin seemingly increases
the beneficial effects of Minoxidil in inducing hair re-growth by stimulating
the growth of the suboptimal hairs. In the treatment of baldness, topical
Tretinoin acts synergistically with Minoxidil to produce denser hair re-growth
than either compound can produce alone.
Efficacy and Clinical Trials on Topical Tretinoin and Minoxidil Combination
Research done in hairless, retinol (Vitamin A)-deficient gerbils have shown
that Topical Tretinoin can induce hair growth. Moreover, only all-trans-retinoic
acid and 9-cis retinoic acid are effective in inducing hair growth as found
in similar studies in mice. Although reports of the combined effect of topical
Tretinoin and Minoxidil in humans are also available; however, it requires
verification by larger controlled studies.
- A combination solution of 0.025% Tretinoin and 0.5% Minoxidil
formulated using generic powder forms showed some hair re-growth on men
with pattern baldness treated 1 to 2 years, a small study found out.
- One study
on male pattern baldness on 36 men subjects treated with a topical mixture
of 0.025% Tretinoin and 0.5% Minoxidil mL twice
for a mean
of 8 to 10 months found out that 44 percent (16 of 36) of the subjects
had a “good” (2:46 percent increase in target area hairs)
response to therapy. Results were compared with a “good” response
in 2 of 12 (16 percent) subjects on 0.025% topical Tretinoin alone,
3 on placebo, and none of 3 on 0.5% topical Minoxidil alone.
of 1mL of 2% topical Minoxidil almost tripled when Tretinoin 0.05%
cream was co-administered once daily vs. 1.3 fold
with placebo as
found by the study of Ferry and colleagues.
- Another study in
men with male pattern baldness compared once-daily topical application
of 0.05% Tretinoin and once daily 2% Minoxidil
application of 2% topical Minoxidil solution. Results found
out that the combined use of the two drugs showed a slight, but not
increase in effectiveness over the use of Minoxidil alone. Moreover,
blood levels did increase with the concomitant use of Tretinoin.
The manufactured formulations of Tretinoin (Retin-A®) and Minoxidil
(Rogaine®), however, are incompatible and become ineffective if compounded
in one formulation. Before the two can be combined, they must be first mixed
while in their generic powder forms or be applied as separate treatments.
Rogaine® must be applied every morning and night, Retin-A® during
the day. However, the skin irritation caused by the Tretinoin and the need
for an extra application during the day is discouraging wide acceptability.
Clinical Side Effects
Potential topical Tretinoin side effects are irritation and photosensitivity;
the potential side effects of Minoxidil should also be considered as it
is combined with Tretinoin. Moreover, concerns about increased irritation,
possible systemic absorption of drug, and difficulties related to the use
of both agents together leads to the limited usage of this line of treatment.