Photo: Tri-Luma, a prescription-strength hydroquinone-steroid-retinoid treatment, is used to treat melasma and dark spots for eight weeks.Since 1982, hydroquinone has been FDA-approved for the treatment of freckles, melasma, and general brown patching. Today, hydroquinone is the most commonly used bleaching agent in the United States. Over time, hydroquinone has acquired a much-deserved high reputation in the dermatology community, as it is considered to be very effective in reducing the appearance of dark spots on the skin. Hydroquinone works by inhibiting the activity of tyrosinase, the rate-limiting enzyme of melanin production, and by increasing the cytotoxicity of melanocytes (melanin-producing cells). However, hydroquinone has been banned in some countries, including France and South Africa, for concerns about increased cancer risk and ochronosis (darkening of the skin) with its use. Recently, the FDA has raised concerns about the use of hydroquinone and other skin-bleaching agents, as they reported that they wish to “establish that over-the-counter (OTC) skin bleaching drug products are not generally recognized as safe and effective.” Does hydroquinone really cause cancer in humans? According to Dr. Susan C. Taylor, M.D., a Philadelphia-based dermatologist in this month's Elle magazine,"The maximum levels of hydroquinone currently allowed (2 percent for over the counter, 4 percent for prescription) aren't dangerous. At worst, it might cause redness or irritation, but only if your skin is sensitive or allergic to the medication." And in a 2006 review in the Journal of the American Academy of Dermatology, Dr. Jacob Levitt, M.D. reports that topical applications of hydroquinone in standard product concentrations are not carcinogenic to humans. According to Dr. Levitt, use of hydroquinone in murine (mouse) studies led to an actual decrease in murine hepatocellular carcinomas (cancerous liver tumors) but an increase in hepatic adenomas (benign liver tumors), suggesting protective effects of hydroquinone. Levitt further reports that murine renal (kidney) tumors caused by use of hydroquinone do not appear relevant to humans after decades of widespread use, and murine leukemia has not been reproducible and would not be expected from small topical doses in humans as well. As such, it seems that topically applied treatments with hydroquinone are safe, as Dr. David J. Goldberg, a clinical professor of dermatology at the Mount Sinai School of Medicine reports, "Over 100 scientific articles confirm it is a safe topical for humans; no independent studies prove the opposite." What is ochronosis? Is there a defined link? Ochronosis is a darkening of the skin that is caused by a build-up of phenylalanine or tyrosine. A literature review by Dr. Jacob Levitt of exogenous ochronosis and clinical studies employing hydroquinone (involving over 10,000 exposures under careful clinical supervision) reveal an incidence of just 22 cases in the U.S. in more than 50 years. The reasons for this phenomenon are not clear, but according to Levitt, it could be a result of the use of skin care products containing resorcinol, an agent often used to treat postinflammatory inflammation as well as melasma, acne, and sun-damaged skin and freckles. Resorcinol is often found in combination with hydroquinone in a hydroalcoholic lotion, but it should not be used by individuals with darker skin types. Ochronosis may also be the result of excess sun exposure while using hydroquinone, as hydroquinone tends to thin the skin, making it more photosensitive, but the sun in turn increases melanin production, reducing the effects of hydroquinone. As such, hydroquinone should always be used with a sunscreen. According to the American Journal of Clinical Dermatology, the majority of patients with ochronosis are Black, but it has been reported to occur in Hispanics and Caucasians as well. Exogenous ochronosis is prevalent among South African Blacks, but is relatively uncommon amongst this population within the U.S. As such, those of African-American descent may wish to take extra precautions in avoiding products with resorcinol and excessive sun exposure when using hydroquinone products. Does hydroquinone appear to be worth the risk? The risks of hydroquinone (see above) appear to be minimal. In contrast, Tri-Luma, a prescription strength retinoid (0.5% tretinoin) steroid (0.01% fluocinolone acetonide) and hydroquinone (4%) has been shown to be effective in treating melasma and general darkening of the skin over the course of eight weeks. According to Dr. Audrey Kunin, M.D., a Kansas-City based dermatologist, Tri-Luma should not be used for longer than eight weeks, as the steroid component may cause the skin to become thinner (and hence more photosensitive and prone to sun-induced signs of aging, etc.) Some other prescription hydroquinone treatments available in the U.S. are Lustra (4% hydroquinone, 4% glycolic acid), Lustra-AF (4% hydroquinone, 4% glycolic acid, SPF 15), and Alustra (4% hydroquinone and retinol). Overall, is hydroquinone safe and effective? Based on the scientific literature, hydroquinone seems to be both safe and effective at this time. Talk to your dermatologist if you are interested in a prescription-strength hydroquinone treatment. Over-the-counter hydroquinone treatments are available in formulations such as MD Skincare Hydra Pure Radiance Renewal Serum ($95.00, Skinstore.com) and Murad Post-Acne Spot Lightening Gel ($58.00, Drugstore.com). If you are using any type of products with hydroquinone, use a sunscreen daily, and try to avoid the sun for best results, and if you are using Tri-Luma, follow doctor's orders and do not use for longer than eight weeks.