Hydroquinone

1. Hydroquinone (HQ) is the most widely used skin depigmenting agent. This agent has a moderate skin depigmenting effect and acts by reducing the number of melanin synthesizing cells in the epidermis.
2. Formulations containing up to 2% HQ are allowed by FDA to be used for skin whitening in normal individuals. These formulations can be purchased in the U.S. as over the counter products. Formulations containing higher than 2% HQ are considered as prescription products and are solely intended for the treatment of hyperpigmentary disorders as melasma. Such products are not allowed to be used for skin whitening in normal subjects.
3. Although HQ alone usually shows a moderate skin whitening activity, the addition of different chemicals to HQ formulations is shown to dramatically enhance its skin depigmenting effect. Some of such formulations can produce a white complexion in black individuals. The best examples of such potent formulations are presented below.

Kligman’s Formula:

• In 1975 Drs. Kligman and Willis combined hydroquinone with tretinoin and dexamethasone and obtained a very potent skin whitening formulation. This formula was capable of producing a white complexion in black subjects after 6-8 weeks of application.
• On the other hand, side effects such as confetti like or non-uniform patchy skin depigmentation did not occur using this combination. Skin atrophy, telangectasia or other side effects of dexamethasone did not occur within the six month period of the study. Possibly, the presence of tretinoin in this formula prevented the occurrence of such side effects. The high efficacy of Kligman’s formula for the treatment of hyperpigmentary disorders especially melasma was also shown by these investigators.
• Although the original Kligman’s formulation did not produce any serious side effects on the individuals during the study course, the possibility of the adverse effects of the long term use of dexamethasone (skin atrophy, telangectasia, etc.) caused other investigators to use less potent steroids instead of dexamethasone in this formulation.

Modified Kligman’s Formulations:

• These formulations contain hydroquinone, tretinoin, and the less potent steroids such as hydrocortisone or triamcinolone instead of dexamethasone. These formulations are also shown to be very effective for skin depigmentation and are considered to be safer than the original Kligman’s formula for a long term use. Modified Kligman’s formulations are applied once daily and it may take 6 to 8 weeks for the eventual depigmenting results to occur.
• Side effects such as transient redness and peeling are common during the first weeks of application.

DID YOU KNOW ?  One of the most important problems with hydroquinone products, generally speaking,  is that they almost always contain thiol compounds (sulphites) which are added as preservatives to prevent hydroquinone decay. These thiol compounds, however, can act as strong sensitizers and may induce cutaneous signs of inflammation or severe allergic reactions including anaphylactic symptoms and life-threatening asthma attacks. Pathak’s Formulation:

• This formula is the combination of hydroquinone and tretinoin without any steroids. The depigmenting effect of this formula is less than the Kligman’s formulation but significantly more than hydroquinone alone.
• This formula does not have the potential side effects of steroid containing formulations but whitens the dark skin to a considerable degree. Pathak’s formula may produce a white complexion in black individuals.
• The high efficacy of this formula for the treatment of melasma is also shown in several studies. A clinical trial, conducted by Pathak et al, involving 300 Hispanic women with melasma showed that cream or lotion formulations containing 2% HQ and 0.05-0.1% tretinoin provided the best results with minimal side effects.

DID YOU KNOW ? Hydroquinone is a hydrophilic chemical, therefore, it does not penetrate the skin very well. It is also shown that the use of a hydrophilic base (vehicle) enhances the depigmenting effect of this agent, perhaps due to the enhancement of its penetration into the epidermis. Hydroquinone plus alpha-hydroxy acids

• Alpha-hydroxy acids (AHAs) are carboxylic acids which have an OH group in the alpha position to their carboxylic group. These acids have natural sources. The most well-known AHAs are glycolic acid (found in sugar cane), lactic acid (found in yogurt) and citric acid  (found in lemon).  AHAs are shown to have several beneficial effects when used on human skin in low concentrations. These acids could increase the epidermal turn over (just like retinoids) and have anti-acne and anti wrinkle effects as well as a weak skin lightening activity.
• Although the skin lightening effect of these acids is not very considerable, they are shown to significantly increase the whitening effect of hydroquinone.  Among the AHAs, Glycolic acid has the lowest molecular weight and is believed to penetrate the skin more readily than the others.
• Hydroquinone-glycolic acid formulations whiten the skin to a considerable degree, but side effects such as transient redness and mild to moderate peeling should be taken into account. The use of these formulas would cause the face skin to become as white as those body areas which have never been exposed to sun light. Therefore, it would be easy for the individual to determine how white he/she can get using such formulations. These formulations also act as moderately potent products for the treatment of melasma and may be chosen as the first line for melasma therapy. Hydroquinone-glycolic acid is applied to the skin once daily and it would take 1-2 months for the eventual depigmenting results to occur.

Hydroquinone-Kojic acid-Glycolic acid

• Kojic acid is a naturally occurring substance which has been widely consumed in Japan as a food additive with the belief that it is beneficial to health. This product is derived from a fungus and its chemical structure resembles ascorbic acid.
• The topical use of kojic acid is shown to whiten the skin. It is shown that kojic acid-glycolic acid formulations may be as potent as hydroquinone-glycolic acid formulations for the treatment of melasma but may be slightly more irritating. On the other hand, it is shown that the addition of kojic acid to hydroquinone products enhances the anti melasma effect of hydroquinone. A combination of the three agents i.e., hydroquinone, kojic acid and glycolic acid is used as an effective treatment for hyperpigmentary disorders.
• Side effects such as transient skin irritation and signs of inflammation may occur during the first weeks of application. It may take about 4-6 weeks for the depigmenting results to appear.

Hydroquinone Controversy: Hydroquinone (HQ) is an antioxidant molecule with skin whitening activity. This agent has been widely used in the topical depigmenting products for many years. It is shown in a clinical study that the use of hydroquinone 3% during a six-year period has not been associated with any types of skin cancer. Português Italiano Tagalog Español русский язык 中文–漢語 Deutsch 日本語