What is hydroquinone?
Hydroquinone is a very popular skin-lightening agent; it is extremely effective, yet extremely controversial. Hydroquinone 4% cream is approved by the Food and Drug Administration (FDA) for treatment of hyperpigmentation such as melasma, chloasma, freckles and senile lentigines.[1]
Hydroquinone for hyperpigmentation
Hyperpigmentation – a darkening of the skin that occurs due to an excess of melanin, for example, in the case of age spots, freckles, melasma, and post-inflammatory hyperpigmentation. Cosmeceuticals are commonly used to target hyperpigmentation; hydroquinone being a common example in the treatment of hyperpigmented skin conditions.
How does hydroquinone work
To understand how hydroquinone helps hyperpigmentation, we must first understand how melanin forms in the skin. Cells called melanocytes convert the amino acid tyrosine into melanin by help of an enzyme called tyrosinase. Since hyperpigmentation is a result of excess melanin we need to target its production somehow. Hydroquinone does just that through inhibition of tyrosinase, decreasing the production of melanin. It also has effects on melanosome formation (the organelle where melanin is made inside the melanocyte) as well as DNA and RNA synthesis.
Hydroquinone is typically very effective in the treatment of hyperpigmentation and hence why it has been widely used. The efficacy and tolerability of hydroquinone 4% cream was investigated in a double‐blind comparative, placebo‐controlled study of 48 patients with melasma.[2] Patients received either hydroquinone cream 4% or placebo twice daily for 12 weeks (with daily suncreen use). Complete clearance of melasma was achieved by 40% of the hydroquinone group compared with 10% of the placebo group.
Safety concerns
However, hydroquinone has recently come under fire due to chronic adverse side effects such as discolouration of the skin, cataract, pigmented colloid milia, loss of elasticity of the skin, impaired wound healing as well as safety concerns. Long-term application of hydroquinone can induce exogenous ochronosis which is characterised by blue-black or gray-blue skin hyperpigmentation and is often irreversible.
Due to recent safety concerns, in the US and Canada, hydroquinone 4% cream is available by prescription only. Previously, hydroquinone products with concentrations less than 4% were previously available over the counter in the US. However, in 2020, the FDA enforced the 2020 CARESAct and Over-the-Counter Drug Monograph Reform, stating that hydroquinone is not classified as Category II and is not generally recognised as safe and effective (GRASE). As a result, the distribution of over the counter (OTC) hydroquinone products are banned. Hydroquinone is also not legally available by prescription or OTC in the European Union, Australia or Japan. Unless prescribed by a doctor, hydroquinone is also banned in the UK.[1,3]
Alternatives
There are safer over the counter alternatives to hydroquinone. Whilst there are several alternatives, vitamin C and tranexamic acid are notable recommendations.
Studies have show that vitamin C acts as a reducing agent at various oxidative steps of melanin formation, hence inhibiting melanogenesis. Thus, vitamin C is widely used in dermatology for depigmentation of hyperpigmented spots on the skin.
Another study compared the use of 5% ascorbic acid and 4% hydroquinone in female patients with melasma and found that there was a 62.5% and 93% improvement in appearance, respectively. Side effects were present in 68.7% of people with hydroquinone use, versus 6.2% with ascorbic acid. Despite hydroquinone being the better performer, vitamin C may have a role to play in the treatment of melasma, since it is mostly devoid of any side effects.[4]
More recently tranexamic acid has become popular for treating hyperpigmentation. Although the exact mechanism of how this molecule works is unknown, studies have found it to be extremely effective. For example, a study of 561 patients treated with oral tranexamic acid twice daily for a median of 4 months, reported a 90% improvement in melasma.[5] There are also many topical tranexamic acid-containing products on the market as of late.
Top tips/important facts
Always speak with a dermatologist first!
Deeper skin tones are more at risk of exogenous ochronosis so exercise with care (consult a dermatologist).
Hydroquinone is not for long-term use. Recommended treatment time is typically 3 months up to one year.
Make sure to wear sunscreen daily.
Hydroquinone should not be used with peroxides so benzoyl peroxide and hydrogen peroxide are off the cards. Since hydroquinone can be irritating it’s also best to avoid hydroxy acids and other potentially irritating products.
Do not use if pregnant or breastfeeding since absorption into the bloodstream is pretty high and there aren’t enough studies showing that it is safe for use during pregnancy/breastfeeding.
Key takeaways
Hydroquinone, whilst extremely effective has several safety concerns which also means that it is a lot harder to get a hold of. But for those with stubborn hyperpigmentation that just won’t quit, hydroquinone may be the answer.
Overall, there may be better alternatives to hydroquinone, taking into account effectiveness and side effects, such as vitamin C serums and tranexamic acid (amongst others).
Top picks
We don’t recommend any products for hydroquinone but suggest consulting a dermatologist if you believe it to be the best option for you. Otherwise, we suggest vitamin C serums and products containing tranexamic acid.
References
[1] Ishack, S., & Lipner, S. R. (2022). Exogenous ochronosis associated with hydroquinone: a systematic review. International journal of dermatology, 61(6), 675-684.
[2] Ennes, S. B. P., Paschoalick, R. C., & Alchorne, M. M. D. A. (2000). A double-blind, comparative, placebo-controlled study of the efficacy and tolerability of 4% hydroquinone as a depigmenting agent in melasma. Journal of dermatological treatment, 11(3), 173-179
[3] Searle, T., Al‐Niaimi, F., & Ali, F. R. (2021). Hydroquinone: myths and reality. Clinical and experimental dermatology, 46(4), 636-640.
[4] Espinal‐Perez, L. E., Moncada, B., & Castanedo‐Cazares, J. P. (2004). A double‐blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. International journal of dermatology, 43(8), 604-607.
