Among the gold standards for skin appearance is a healthy, even complexion. Unfortunately, there are many causes of dyspigmentation that can occur, and one of the most common is melasma. This is a hyperpigmentation disorder that results in the appearance of flat, dark brown to grayish brown patches on both sides of the face.
Hydroquinone has been the go-to treatment for melasma for decades. Following its initial discovery, research on this powerhouse ingredient has continued, leading to more effective and safer formulations.
So how exactly does hydroquinone work to lighten melasma lesions? To answer that, we must first understand how melasma develops.
Melasma 101
In simple terms, melasma occurs when melanocytes produce more melanin than usual. This pigment could be deposited in the epidermis, the superficial layer of the skin, or dermis, the layer right underneath it. To the naked eye, it appears as flat, dark brown to grayish-brown patches that appear symmetrically on the face. There are different patterns of distribution, but the most common locations include the forehead, cheeks, nose, and chin.
There appears to be no singular cause for melasma--rather, it is a multifactorial disease (Bandyopadhyay, 2009). It is likely that there is some abnormality in the processes that control melanin production. Genetics, family history, and hormonal imbalances clearly play a role. External influences include administration of certain kinds of drugs, cosmetics, and skincare products. Last but not least, sun exposure and lack of sun protective measures is a likely culprit in the exacerbation of melasma, as well as many other hyperpigmentation disorders.
Approximately 1% of the global population suffers from this condition, but within certain populations, it can be much higher. Those with darker skin types (Fitpatrick IV to VI) and Asian, African, or Latino descent are more likely to have melasma (Pichardo et al., 2009). It is more common in women than in men, particularly those of reproductive age (Shankar et al., 2014). In pregnant women, melasma is also called “chloasma” or the “mask of pregnancy”.
Though melasma itself does not pose a health risk, both anecdotal and scientific evidence has shown it has a considerable effect on one’s psycho-emotional wellbeing (Fatma et al., 2016; Jiang et al., 2017). In an effort to improve the quality of life of melasma patients, decades of research have been dedicated to understanding the disorder and finding its cure.
There are a number of ingredients used to lighten melasma marks, but the top choice for many dermatologists is hydroquinone.
How does hydroquinone work?
Hydroquinone’s effectiveness as a skin bleaching agent relies primarily on its molecular structure. It is very similar to that of L3,4-diphenylalanine, (L-DOPA) a melanin precursor--so similar in fact, that the enzyme that usually binds to L-DOPA, which is called tyrosinase, ends up binding to hydroquinone instead. This is bad news for skin pigment production, as this particular enzyme is responsible for converting L-DOPA to melanin. As a tyrosinase inhibitor, hydroquinone effectively ambushes the production of melanin.
There is another way that hydroquinone throws a wrench into the process of skin pigmentation: it damages the cells responsible for producing melanin, called melanocytes. Over time, the number of microscopic pigment-making factories decrease, vastly slowing down the darkening of skin.
Hydroquinone’s two-fold approach to inhibiting melanin deposition makes it excellent at treating melasma. It has retained the top spot as the drug of choice for melasma, with studies showing upwards of 70% of patients seeing significant improvements within 3 months of twice daily use. It is particularly effective at addressing melasma cases wherein the melanin is deposited in the epidermis, or topmost layer of the skin.
What are the indications for hydroquinone use?
Hydroquinone’s potency as a depigmenting agent makes it ideal for use in a wide variety of hyperpigmentation disorders. Melasma is one important example, but there are others.
Post-inflammatory hyperpigmentation is caused by excessive melanin production in response to an injury or infection. Thermal burns, acne, skin infections, and razor bumps may leave behind a darkened area that persists for much longer than it took to heal the initial insult. Hydroquinone has been used to speed up skin lightening to great effect, as soon as the inflammation has already been controlled.
Solar lentigines, also known as sun spots or liver spots, occur because of intense or prolonged sun exposure without proper protection. This may occur because of decades of sun damage, as in older individuals, or among those who regularly use the tanning bed. Hydroquinone can address existing spots, but nothing beats sun protection measures in preventing new ones from appearing.
Certain drugs, such as the ones used in chemotherapy, may cause changes to the skin. Dryness, irritation, inflammation, and hyperpigmentation can occur. For the latter, hydroquinone may be used in the cases were the dark spots persist after cessation of therapy.
Hydroquinone has also been used to prevent and treat hyperpigmentation caused by laser treatments. Since one complication of these types of resurfacing techniques is increased melanin production, bleaching creams have been used to minimize the chance of occurrence.
It is common clinical practice to apply hydroquinone for a period of time before laser treatment, but a study by West and Alster (1999) shows that this has no noticeable effect. The plausible reasoning is because the skin layers that grow after laser resurfacing include melanocytes that were not exposed to the topical bleaching agent. However, the skin-lightening effects of hydroquinone use after laser therapy is well-documented.
What are factors to consider before using hydroquinone for melasma?
In recent years, concerns have been raised about the safety profile of hydroquinone. In some countries, the ingredient has been banned or is purely on prescription basis. There is some controversy in the medical world about this ban, with some arguing that it is overly extreme (Levitt, 2007). This belief is compounded by studies that show that the most frequent cause of adverse side effects are patient misuse and use of unregulated hydroquinone-containing products, rather than the danger of the compound per se. patients use more concentrated formulations, and increase the frequency of application outside of their doctor’s orders. In fact, the American Society of Dermatologic Surgery Association released a position paper opposing the additional restrictions on hydroquinone products.
Hydroquinone use has been associated with irritant or contact allergy dermatitis, causing dryness, redness, itchiness, increased sensitivity to the sun, and a painful stinging sensation when applied. However, these are often mild and transient. Use of hydroquinone in tandem with other skincare or cosmetic products with irritating ingredients, exacerbating the irritation of already sensitized skin.
More lasting effects on the skin include the formation of colloid milium and milia, which are small bumps on the skin that may or may not be pigmented. Discoloration of the nails and skin may also occur, but these are rare occurrences.
Exogenous ochronosis, or the formation of bruise-colored patches on the skin, has long been associated with hydroquinone use, but it appears this condition develops when high concentrations of the ingredient are used frequently over a long period of time. The risk of this occurring when doctor’s orders about concentration and dosage are followed is very slim. A systematic review of exogenous ochronosis case reports found that it is most likely to occur in patients who use over 4% hydroquinone products over an average of 5 years (Ischak and Lipner, 2021).
Perhaps the most worrying safety issue associated with hydroquinone use is carcinogenicity. Oral administration on lab animals has shown that the ingredient can trigger the development of cancerous growths (Kooyers and Westerhoff, 2004). However, this result has not been found in the many human studies on topical hydroquinone use, nor have there been reports of its occurrence in clinical practice despite half a century of use (McGregor, 2007; Sofen et al., 2016).
So far, no studies have shown that hydroquinone is teratogenic. Its safety in lactating women is not yet known. However, since 35-45% of the drug gets absorbed into the bloodstream through topical administration, it is advised that pregnant and lactating patients err on the side of caution and opt for other skin lightening measures.
As with any drug, it is best to consult a health professional prior to using hydroquinone. To ensure that this medication is the appropriate treatment, a dermatologist should confirm the diagnosis, take a thorough history, examine the patient’s skin, and conduct other diagnostic tests, if necessary.
How is hydroquinone used?
Hydroquinone is administered topically by applying a thin layer on hyperpigmented areas. To treat melasma, dermatologists will usually suggest 1-2 times daily administration for at least 3 months. Proper and even application is essential, as failure to do so may lead to irregularities in color.
Regular consultation with a dermatologist throughout the treatment period is important to assess the patient’s response. Adjustments can be made on the prescription depending on the rate of improvement and occurrence of side effects.
Hydroquinone can be continued even after resolution of melasma as maintenance therapy. This usually means scaling down the frequency to 2-3 times a week.
What formulations are available?
Formulations for melasma usually contain 1-5% hydroquinone. In some countries, it is possible to buy over-the-counter products at 2% concentration or less. However, in other areas, a prescription is required to purchase hydroquinone-containing products, regardless of concentration.
It is available as a solution, emulsion, cream, or gel. Some products use hydroquinone as the sole active ingredient, while others use it in combination with other ingredients for added skin benefits. Generally, these are known to perform better and with less side effects (Gupta et al., 2006). These include vitamin A derivatives, antioxidants, anti-inflammatories, alpha-hydroxy acids, among others.
Kligman’s formula is one of the most prescribed products for melasma. It is a combination of hydroquinone, tretinoin, and a corticosteroid. The original formula started as 5.0% hydroquinone, 0.1% tretinoin, 0.1% dexamethasone (Kligman and Willis, 1975). The addition of tretinoin is meant to improve penetration, add additional depigmenting power, and improve the texture and appearance of skin. Dexamethasone was included to counter the inflammatory and irritating effects of the other two ingredients.
Over the years, many modifications to the Kligman’s formula have been made--the concentration of the components may change, corticosteroids other than dexamethasone may be used. Generally, triple combination creams have been shown to be more effective than hydroquinone monotherapy (Ferreira Cestari et al., 2007) and double combination therapy (Taylor et al., 2003).
Clinical trials are continuously being done to find the best iteration of the triple combination cream, one that is able to deliver the medication in the safest and most effective way possible.
How to maximize the effects of hydroquinone
Hydroquinone is great at doing its job, but if you want to take full advantage of its benefits and minimize potential adverse side effects, there are a number of things you can do.
Use sun protection
Melanin production is triggered by sun exposure--no doubt about it. So if you want to treat melasma, you have to lighten existing marks and stop new ones from popping up. Hydroquinone will also sensitize your skin against UV radiation, so protecting it becomes even more important.
While sunscreen is definitely a pillar of sun protection, take note that it’s only one among many. Using a broad spectrum, high SPF sunscreen is important, but so is using protective clothing, minimizing sun exposure, and seeking shade.
Buy from a reputable source
It may be tempting to buy hydroquinone products at a fraction of the cost, but you might be getting more than you bargained for. Buy from official stores if you are considering using an over-the-counter product. Consult your dermatologist about where to purchase their prescribed hydroquinone products.
Study your skincare regimen
Hydroquinone is a potent drug that will certainly have an effect on the skin. It does not always take kindly to being used alongside other ingredients. So before making the jump, take a good hard look at the skincare products you have on the shelf, and do research on whether they could react with hydroquinone.
If you are consulting with a doctor, they will likely provide a holistic melasma treatment plan that contains all the products you need to use.
Do a patch test
This should be standard protocol whenever trying out a new product on your skin. Apply hydroquinone in a small patch of skin, and observe for reactions for 24 hours. Red flags include prolonged itching, redness, swelling, heat, or pain.
Listen to your skin
Everyone’s skin reacts differently, so pay attention to yours. Look for hallmarks of inflammation and irritation, and pay attention to when they occur. Take pictures of your skin’s progress to see if the hydroquinone is working. Learning to listen to your skin can help you determine if this skincare regimen is working for you, or if you need something else to treat your melasma.
This content is for general information only and is not a substitute for medical advice.
References:
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Fatma, F. & Baati, Imen & Mseddi, M. & Sallemi, R. & Hamida, Turki & Masmoudi, Jawaher. (2016). The psychological impact of melasma. A report of 30 Tunisian women. European Psychiatry. 33. S327. 10.1016/j.eurpsy.2016.01.1130.
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