Shining a light

Dr Ifeoma Ejikeme on why hydroquinone is the gold standard for skin brightening

Aesthetic Medicine (AM): What is hydroquinone?

Dr Ifeoma Ejikeme (IE): Hydroquinone is a skin lightening, skin-brightening product, and it’s been used for a very long time in aesthetics, specifically in dermatology. It’s a prescription medication used for the management of conditions such as melasma, post-inflammatory hyperpigmentation, certain benign legions and lentigines, and it is the bread and butter, the standard of care, particularly for conditions like melasma.

AM: How does it work?

IE: Specifically, it works as a depigmenting agent. It inhibits an enzyme that’s very important in the pigment or the melanin pathway, known as tyrosinase. It interferes with the synthesis of melanin by blocking tyrosinase activity, so it reduces dark spots appearing on the skin.

AM: What is the current controversy currently around hydroquinone?

IE: If you look at any single prescription medication, there’s a therapeutic window: there’s a way in which it can be used to give a good clinical effect, and there’s a way it can be used, where you can get bad clinical effects or side effects.

Outside its therapeutic window, hydroquinone can have known and documented side effects and potential complications including lightening the skin, hypopigmented patches, disorganised pigment, or mottled pigmentation, as well as a condition known as ochronosis, which is a bluish-grey discolouration in the skin. Another reason why there is specific controversy about hydroquinone as a prescription medication, unlike others, is that some of the reasons it’s used may be felt to be cosmetic.

AM: Are the risks worth the benefits? Are there any other things that you can try which would give the same clinical benefit?

IE: As with any medication, you should always try the treatment with the least potentially harmful effects first. In lighter skin types, there are lots of other potential options that you can use that may give the same clinical benefits. As we said, hydroquinone is a tyrosinase inhibitor, and other tyrosinase inhibitors work in lots of different ways, such as arbutin, kojic acid, cysteamine and thiamidol, which is a newer one. Tranexamic acid blocks tyrosinase in a slightly different way. However, none of these have reached a standard to be deemed to be a prescription medication. Hydroquinone is still known to be the most effective prescription medication. That doesn’t mean the others don’t work; it means that they offer a certain level of improvement, but hydroquinone is the gold standard for conditions such as melasma.

Scheme of the biosynthetic pathway of eumelanins and pheomelanins. The activities of tyrosinase are indicated in the scheme. Moreover, the enzyme can oxidise DHICA to its o-quinone directly, or it can oxidise DHICA and DHI indirectly via the formation of o-dopaquinone. TRP2 (dopachrome tautomerase) or Cu2+ can participate in the evolution of dopachrome to DHICA. The oxidation of DHICA can be catalysed by TRP1, (DHICA oxidase), tyrosinase or Cu2+. When glutathione or L-cysteine attack o-dopaquinone, glutathione-dopa or cysteinyl-dopa adducts are formed and these later evolve to pheomelanins.

AM: Does that mean that others will have less effect or are milder?

IE: Absolutely. As with anything prescribed and deemed to reach a certain level of efficacy, it comes with risks. It must be used in a very controlled way under the guidance of a medical aesthetic practitioner.

Even then, these products aren’t risk-free. However, it means that the therapeutic window can be respected. Some studies have come out that have said that other treatments, including cysteamine, may be as effective as 2% hydroquinone when used over a longer period. In the UK, the standard of care in terms of hydroquinone means you can get 2% to 4%, and you can compound higher percentages, which may be required in specialist treatments. Hydroquinone is the gold standard against which all other pigment regulators are benchmarked. However, we’re always looking for more effective, better, safer options.

I’ve used many different types of tyrosinase inhibitors, and they all have their place depending on the person that you’re treating and the treatment that you’re doing.

AM: What about darker skin types?

IE: It depends on what you’re treating. If you’re doing a resurfacing laser, or you’re a very intense medium depth or deep peel and you want to regulate the pigment more or you want to do a deeper treatment, you need something that’s going to be extremely safe for your patients.

This is true for all skin types, but it’s particularly important when there’s more melanin, as there is a higher risk that the treatment can trigger excess pigment. When you’re doing medical-grade treatments, you want to have as much control as possible.

For a lot of the protocols that are used globally, when working with darker skin types, you prepare the skin with hydroquinone because it means that you can do a safer, more effective treatment.

AM: How long should hydroquinone be used?

IE: If hydroquinone is used outside its therapeutic window, e.g. over years and years, unregulated or mixed with other substances, the incidence of problems skyrockets.

Various protocols and practices help minimise the problems e.g. when it is either cycled two months on, two months off or used for six months and then weaned off.

In this context, when used in a regulated, formulated manner, it is much safer and very different to what you may find on the black market, where there is a high incidence of complications because it has been mixed with things like steroids or mercury to potentiate its effect. Those combined products can lead to severe complications.

Hydroquinone, even by itself, can cause complications. It must be applied under the guidance of a medical aesthetic practitioner. who knows how to use it, the signs to look out for in the skin indicating you need to ween onto another treatment protocol and never be used longer than needed.

AM: Aside from using it for too long, what are the other ways in which somebody could misuse hydroquinone?

IE: It should only be used for a clinical indication, such as post-inflammatory pigmentation or melasma, and then only under the guidance of a medical aesthetic practitioner. .

AM: Going forward, do you think it will continue to be the gold standard?

IE: Individual people can have views about whether they like it or not. This is the same with pretty much every prescription medication. We all have ones that we like and ones that we don’t like. Currently, it is the standard of care because it’s the only prescription medication for the management of severe conditions of pigment.

The world is changing, in terms of the impact pigmentation has on everybody. It is getting hotter, so there are more disorders of pigment happening and, as a planet, we’re becoming much more of a milieu of skin tones, which means that hyperpigmentation will not only be an issue but continue to increase.

Because of this, there definitely needs to be more research into alternative hyperpigmentation treatments that are consistently effective. There’s currently a paucity of excellent pigment regulators for disorders of the skin, aside from hydroquinone. If we think about any other class, there are many different types. For analgesia, there is everything from paracetamol to morphine, but when it comes to prescription skin-brightening agents, there are not that many.

Over the counter, there are lots, everything from vitamin C, tranexamic acid, with cysteamine and thiamidol being some of the newer ones. I think many more will come out, as well as more formulations that blend them together, to block the production and the distribution of melanin.

If that happens and you’re getting truly equivalent results it would become the gold standard and you won’t have to rely on hydroquinone. They’re not there yet, but I’m hopeful that in the future this will happen.

DR IFEOMA EJIKEME

Dr Ifeoma Ejikeme is a renowned figure in medical aesthetics. She is the current holder of the highly esteemed Aesthetic Medicine Award for Best Aesthetic Doctor UK, adding to her accolades including Marie Claire’s Best Aesthetic Doctor 2021 and Tatler’s Top Doctor 2022. A trusted voice in the field, she publishes globally referenced medical papers and regularly offers media expertise at conferences, top-tier titles and major news outlets.