Hydroquinone: Friend or Foe?

John E. Kulesza
Many skin care practitioners face challenges treating hyperpigmentation due to its complex and recurrent nature. The most widely used topical medication for hyperpigmentation management is Hydroquinone, a compound used since the 1960s.

Over the years, health care regulators in certain countries have raised questions about the safety of Hydroquinone. In some cases, this resulted in placing limitations on the commercial sale of Hydroquinone-containing products. In 2006, the U.S. Food and Drug Administration (FDA) published its intention to eliminate Hydroquinone from OTC drug products. FDA based its position mainly on reports of pigmentation abnormalities associated with Hydroquinone-containing products in countries outside the U.S.. As of March 2011, FDA has taken no action and apparently continues to review data on the drug.

So, is Hydroquinone a therapeutic friend of foe? When a patient presents with hyperpigmentation, should you recommend or prescribe it? To answer this question, let's review some basics of Hydroquinone chemistry.

This illustration is some chemical 'shorthand'.  Each intersection of two lines represents a Carbon atom. Consequently, the 6 intersections shown in each molecule are 6 Carbon atoms joined together into a ring. To satisfy the chemical bonding requirements of the Carbons, we must attach one Hydrogen atom to each of them. Note the Hydrogens aren't shown, but organic chemists know they exist. The circles drawn inside the rings represent a double bond, i.e. two shared electrons, that moves from one Carbon to the next. This is needed to satisfy the Carbons' bonding requirements when they form a ring.

The compound on the left is Benzene, an oily industrial chemical that is toxic and carcinogenic. Clearly this is a substance to be avoided.

If one Oxygen atom is added to the top Hydrogen a new compound is created: Phenol. This substance is more toxic than Benzene. It has the ability to rapidly kill living cells, but it's not considered carcinogenic in humans. Ironically, the cytotoxicity of Phenol can be put to good use. Our bodies are constantly challenged by various environmental microorganisms and our immune systems aren't always able to fight them off. Phenolic drugs, i.e., drugs that incorporate the chemical structure of Phenol in them, can save lives by killing the offending microorganisms. These drug molecules modify the toxicity of Phenol to make it harder for it to harm our own cells. Other examples of Phenolic compounds are Benzyl alcohol, which is used as a preservative in injectable drugs, Aspirin, and even Green Tea. Just because something resembles Phenol doesn't necessarily mean it's bad for you!

If one more Oxygen atom is added to the bottom Hydrogen of Phenol, the result is Hydroquinone. We know this compound is helpful in treating hyperpigmentation disorders. However, it resembles two dangerous substances, Benzene (a known carcinogen) and Phenol (a poison). Perhaps now it becomes clearer why regulators worry about Hydroquinone. The underlying question is to what extent does Hydroquinone share the 'bad' characteristics of its chemical cousins?

Unfortunately, we don't have a clear answer to this question right now. Four decades of data from the U.S. yield very few reports of toxicity. Pigment abnormalities, cited by FDA, were reported mainly outside the U.S., where skin depigmenting products may contain other toxic ingredients combined with Hydroquinone, such as Mercury. It's possible that use of Hydroquinone from reputable suppliers at the commonly used concentrations of 2-4% will be shown to be unequivocally safe in further studies.

Additionally, FDA cites certain studies where tumors appeared in animals fed high doses of Hydroquinone. But are such studies relevant? Obviously, we aren't asking patients to eat Hydroquinone in order to treat hyperpigmentation. It is only applied topically and therein lies additional safety: the two hydroxyl groups (OH) on this molecule confer water solubility that limits its ability to penetrate into the skin. Indeed, the “good news” here is the poor penetration of Hydroquinone makes significant systemic absorbtion unlikely. The “bad news” is this water-solubility can prevent Hydroquinone from reaching melanocytes deep in the skin, thus reducing efficacy.

What’s the bottom line on Hydroquinone? Until we hear otherwise from FDA, this drug can be used as directed in product labeling for treating hyperpigmentation. The key words here are "as directed." My recommendation is to follow such directions, which are FDA approved, to the letter. I wouldn't recommend doses beyond the 4% level, nor use beyond the time period specified. Sticking to such a simple approach will protect both practitioner and patient, and will likely keep Hydroquinone a therapeutic ”friend” for some time.

John E. Kulesza is founder and President of Young Pharmaceuticals, Inc., a 34-year old firm based in Hartford, Connecticut, that develops and markets proprietary dermatology products to dispensing physicians.  Kulesza, an industrial chemist by training, holds several U.S. patents on dermatological techniques includingdrug delivery systems and prescription drugs.  A graduate of Yale University, he is the principal formulator of one of the best-known physician-promoted consumer product lines on the market today and scientific advisor to several multi-national skin care manufacturers.

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