Tretinoin in Hair Loss Formulas

June 27th, 2023
Samual Abiola
Pharm.D. Candidate 2024
Philadelphia College of Pharmacy

Tretinoin is a retinol(vitamin A derivative) that is used to treat skin issues like acne and wrinkles. However, it is now showing promise in treating hair loss as well.

Androgenetic alopecia or hair loss is defined as the progressive loss of hair any time after puberty and affects about 50% of males and females in the US anually. Hair loss is believed to be caused by a hormone called dihydrotestosterone or DHT. DHT is a derivative of the hormone testosterone. Testosterone is converted into DHT by an enzyme called 5-alpha reductase(5-AR). Hair follicles that have a high sensitivity to DHT tend to shrink, have a shorter anagen phase( growth of hair follicle) and remain in the telogen phase( rest phase of hair growth cycle) longer. This ultimately leads to noticeable loss of hair on the scalp and possibly even complete baldness.

The most common product use to treat hair loss is minoxidil. Oral minoxidil is used to treat high blood pressure by dilating the arteries, but when it is applied topically to the scalp, the increased blood flow can stimulate hair growth. However, minoxidil is not effective for everyone who uses it. This is because minoxidil is not what actually promotes the growth of new hair. When topically absorbed, minoxidil is converted into minoxidil sulfate by sulfotransferase enzymes in the body. Minoxidil sulfate is what stimulates hair growth and it cannot be available commercially because it is chemically unstable. Therefore, the effectiveness of minoxidil is based on how well the sulfotransferase enzymes in the body can convert minoxidil into minoxidil sulfate. However, the problem is that sulfotransferase activity can vary wildly from person to person due to genetic factors. This means that some people will have high sulfotransferase activity and respond well to minoxidil treatment while others with low sulfonyltransferase activity will not have a great treatment response because minoxidil cannot be converted into its active form minoxidil sulfate.

The value of tretinoin comes in when treating those who do not respond to minoxidil. Tretinoin can help increase the efficacy of minoxidil. According to one study, where participants were given either minoxidil twice daily or minoxidil plus tretinoin once daily, the results were that minoxidil plus tretinoin once daily was just as efficitive in stimulating hair growth as minoxidil by itself twice daily. This is important because nonadherence contributes to minoxidil`s lack of efficacy. It is much easier to apply at treatment once a day than twice a day. Tretinoin helps upregulate sulfonyltransferase activity and thus increase minoxidil efficacy. Tretinoin may also increase the absorption of minoxidil through the skin. According to one study, tretinoin increased minoxidil absorption through the scalp by nearly three times.

Tretinoin could be a breakthrough treatment in hair loss. Minoxidil, the only FDA approved hair loss treatment product is still not effective for many people. Tretinoin appears to significantly increase the efficacy of minoxidil. One of its greatest strengths lies in the fact that patients taking minoxidil/tretinoin will only need once daily application as opposed to twice daily application with minoxidil alone. This will greatly improve adherence and thus improve efficacy of treatment. However, it is important to remember that tretinoin is still only FDA approved for skincare, so it has to be prescribed by a provider off-label and compounded in combination with minoxidil at a pharmacy in order to treat hair loss. A minoxidil/tretinoin combination product could be the solution that many people are looking for to their stubborn hair loss problems.

References:

1. Ho CH, Sood T, Zito PM. Androgenetic Alopecia. [Updated 2022 Oct 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430924/
2. Shin, H.S., Won, C.H., Lee, S.H. et al. Efficacy of 5% Minoxidil versus Combined 5% Minoxidil and 0.01% Tretinoin for Male Pattern Hair Loss. AM J Clin Dermatol 8, 285-290 (2007). https://doi.org/10.2165/00128071-200708050-00003
3. Ferry, J.J., Forbes, K.K., VanderLugt, J.T. and Szpunar, G.J. (1990), Influence of tretinoin on the percutaneous absorption of minoxidil from an aqueous topical solution. Clinical Pharmacology & Therapeutics, 47: 439-446. https://doi.org/10.1038/clpt.1990.55