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Hydroquinone alternatives effective in milder cases of hyperpigmentation


Although numerous hydroquinone-free compounds for skin lightening are available, their effectiveness depends on the severity of the condition, according to Marta Rendon, M.D., who practices in Boca Raton, Fla.

Key Points

"One aspect is a mild skin-lightening effect and the other aspect is significant clearing of the problem. If the person has a very mild, superficial pigmentary problem, many of these products might work and get them a little bit lighter. But if they have more serious issues, they are going to need a prescription product like hydroquinone," Dr. Rendon says.

Skin lightening

Melasma, known as the mask of pregnancy, is thought to be a cutaneous disorder associated with an overproduction of melanin by the tyrosinase enzyme. It is sometimes triggered by pregnancy, but is also related to birth control pills, menopause, fluctuating hormones, and, in some cases, genetic predisposition. Pigmentary alterations are also seen in patients with photodamage.

"Patients have blotchy irregular pigment and they want to even their skin tone. Also, some patients have postinflammatory hyperpigmentation, which is very common after acne and other skin disorders," Dr. Rendon says.

The regulatory status of over-the-counter (OTC) skin bleaching drug products containing hydroquinone, a popular agent for skin lightening, is pending. In the interim, hydroquinone remains available as an OTC drug product and in some prescription formulations.

Previous research has shown that hydroquinone may act as a cancer-causing agent, or carcinogen, in rodents such as rats and mice after oral administration, according to the Food and Drug Administration. It also has been linked with ochronosis, a medical condition in humans known as skin darkening and disfiguration, when it is applied topically.

"I use hydroquinone on my patients every single day and we have no trouble," Dr. Rendon says. "I do not see any carcinogenic side effects in my practice. The other dreaded side effect is ochronosis, and that has not happened (in my practice) with even low amounts. It is an individual sensitivity to developing the problem."

Ongoing research

New research is attempting to zero in on the causes of pigmentary abnormalities. In melasma, it is known that the amount of melanin rises to increase melanogenesis. Therefore, researchers are attempting to find agents that curtail that process, including transcriptional enzymes, RNA and tyrosinase-related protein-1 (TRP-1). It is thought that TRP-1 might be one of the enzymes involved in the pathogenesis of melasma, according to Dr. Rendon.

Several new studies have been conducted outside the United States, including treatment with resorcinol1 in 20 patients with melasma in Seoul, South Korea. Treatment included 4-n-butylresorcinol, which is a resorcinol derivative that appears to have an inhibitory effect on both tyrosinase and TRP-1.

"Patients in this study had some improvements in their melasma," she says.

Another recent study in 28 Asian women in Suwon, South Korea used alpha bisabolol to successfully treat hyperpigmentation.2

"They determined the patients had improvement in pigmentation," Dr. Rendon says.

Skin lightening agents

Newer prescription skin lightening products on the market are often combination products with hydroquinone. For example, hydroquinone is combined with retinoic acid, retinols, or in combination with vitamin C or glycolic acid. Sometimes a mild steroid is added to reduce irritation.

"The companies are trying to potentiate the effects of hydroquinone by adding in other ingredients, but the basic one is hydroquinone," Dr. Rendon says.

Nonhydroquinone ingredients, such as niacinamide and soy, have some efficacy. Some of the over-the-counter products that have these ingredients show some skin lightening effect, but not for severe issues, she says. Kojic acid is another ingredient used for skin lightening.

"Its use has been discontinued in Asia and Japan because people reported skin irritation and in sensitive skin it is a problem," Dr. Rendon says.

Arbutin, bearberry and mulberry are also used for skin lightening.

"These are pretty safe and they are often mixed in a lot of these OTC natural products that have some lightening properties," she says. Bearberry and mulberry extracts convert into arbutin, Dr. Rendon says.

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