Hydroquinone

Hydroquinone (1,4-dihydroxybenzene) is an organic compound from the phenol group, characterized by a benzene ring which, in contrast to phenol (carbolic acid), is substituted at two opposite positions with hydroxyl groups (-OH). This structure enables hydroquinone to act as an effective reducing agent.

Hydroquinone acts by inhibiting the enzyme tyrosinase, which plays a key role in the biosynthesis of melanin. Tyrosinase catalyzes the first steps of this synthesis by oxidizing the amino acid tyrosine to dihydroxyphenylalanine (DOPA) and then to DOPAquinone, which is then further converted into various forms of melanin.

Hydroquinone competes with tyrosine for the binding site on tyrosinase, which prevents the conversion of tyrosine to DOPA. This leads to a reduced production of melanin and consequently to a lightening of the skin in the treated areas. In addition, hydroquinone's antioxidant properties can reduce the melanin pigments that have already formed, which also helps to lighten the skin.

Hydroquinone penetrates the human forehead skin in vivo after a single topical exposure in an alcoholic vehicle of 24 hours duration. Percutaneous absorption is rapid for all hydroquinone preparations, and peak elimination was reached within the first 12 hours after application. Elimination was completed within 5 days (Bucks DA et al. 1988).

UVA+UVB or UVA irradiation increased hydroquinone flux fivefold.

A negligible change in hydroquinone permeation was observed with UVB exposure. Hydroquinone shows a lower penetration through senescent skin than through young skin.

In the case of vitiligo, melanoma and suspected melanoma, acute inflammation and eczema of the skin, perioral dermatitis, rosacea and all the usual restrictions on the use of cortisone preparations, such as chickenpox, vaccination reactions, skin infections caused by bacteria or fungi and specific skin processes (syphilis, tuberculosis) and kidney disease, hydroquinone-containing topical preparations should not be used.

Apply a thin layer to the altered skin once a day. Treatment duration 6-12 weeks. Discontinue treatment if the skin does not lighten after 3 months at the latest.

Use in children: Hydroquinone is not intended for use in children under 12 years of age.

Hydroquinone is applied topically as a cream and is usually used in concentrations between 2 and 4% hydroquinone. The highest over-the-counter concentration of hydroquinone in the USA is 2%, while formulations for medical treatment are usually prescribed at 4%. Generally, creams with hydroquinone are considered unstable, regardless of the concentration, as the active ingredient oxidizes very quickly and thus becomes ineffective, which is visible by a brown discoloration of the preparation (Draelos ZD et al. 2014).

Note! Controversial therapeutic principle, perform an epicutaneous test before use! Negative monograph! A combination preparation (see 3% hydroquinone formulation below) is preferable to monotherapy.

Allergic reactions, permanent depigmentation, risk of inducing vitiligo (especially in dark-skinned people).

Anyone who uses products containing hydroquinone to lighten the skin risks skin cancer with unchanged UV exposure due to the loss of pigment. The risk of malignancy increases threefold compared to the general population.

Animal experiments have shown a suspected mutagenic and weakly carcinogenic effect after feeding with hydroquinone. The duration of topical application in humans should therefore depend on the success of the therapy and be kept as short as possible, even if it is applied externally with only a low intake.

Exogenously acquired ochronosis (Ishack S et al. 2022) is a side effect that should not be underestimated with long-term (>3 months) extensive application of 3-4% hydroquinone-containing bleaching creams.

Long-term use of hydroquinone can lead to the development of exogenous ochronosis, which is histologically similar to endogenous ochronosis of alkaptonuria. As with endogenous ochronosis, exogenous ochronosis is manifested by ochre-colored pigments in the histological section of the connective tissue of the dermis and is also visible macroscopically as a bluish-brown discoloration of the skin (Lazar M et al. 2023).

Ingestion of larger quantities of hydroquinone can lead to intoxication. 2 - 5 g are considered lethal. Symptoms of intoxication are vomiting, vertigo, shortness of breath, delirium and shock. Countermeasures include absorption-reducing measures (activated charcoal) and symptomatic therapy.

See also the depigmenting 3% hydroquinone ointment.

Finished preparations are available with the 5% hydroquinone cream Pigmanorm® (Widmer).

• Hydroquinone is often used in combination with tretinoin and hydrocortisone.
• Hydroquinone is known to be a very effective skin lightening agent. Recently, over-the-counter skin lightening products containing hydroquinone have been banned in the USA. This has led to the safety of this widely used agent being increasingly questioned (Shivaram K et al. 2024).

1. Bhattar PA et al.(2015) Exogenous Ochronosis. Indian J Dermatol 60:537-543.

2. Blumeyer A et al (2016) Progressive hyperpigmentation of the face. Dermatologist 67: 922-924

3. Bucks DA et al. (1988) Percutaneous absorption of hydroquinone in humans: effect of 1-dodecylazacycloheptan-2-one (azone) and the 2-ethylhexyl ester of 4-(dimethylamino)benzoic acid (Escalol 507). J Toxicol Environ Health 24:279-280

4. Draelos ZD et al. (2014) A Method for Maintaining the Clinical Results of 4% Hydroquinone and 0.025% Tretinoin With a Cosmeceutical Formulation. Journal of Drugs in Dermatology 4: 386-390.

5. Ishack S et al. (2022) Exogenous ochronosis associated with hydroquinone: a systematic review. Int J Dermatol 61:675-684.

6. Lazar M et al. (2023) Exogenous Ochronosis: Characterizing a Rare Disorder in Skin of Color. J Clin Med 12:4341.

7. Kerscher M et al. (2020) Topical treatment of pigmentary disorders with cosmetic and pharmaceutical agents. Dermatologist 71:944-949.

8. Shivaram K et al. (2024) An update on the safety of hydroquinone. Arch Dermatol Res 316:378.