Hydroquinone Risks

You finally got rid of dark spots and melasma with your personalized hydroquinone cream?  Is the immediate results worth the long term risk?

Everyone wants beautiful, even, glowing skin.  In this age of instagram, we want results now. Offerings of high dosage hydroquinone at 12% are easily available through online services without the need to see a doctor in-person.  There has been an increase in privately dispensed or physician based lines of various hydroquinone formulations and these products have not undergone clinical study or FDA evaluation. It is this genre of hydroquinone products that have raised safety and health concerns. Such compounded medications are not regulated in their formulation or preparation and therefore may pose potential safety concerns. Are these aggressive use of hydroquinone safe? 


What is hydroquinone?  

Hydroquinone also known as benzene-1,4-diol or quinol, is a reducing agent and has two main uses: 

  1. It is a major component in most black and white photographic developers for film and paper. 

  2. A skin lightener 

As a skin lightener, hydroquinone works at the cellular level to reduce the synthesis of melanin. The dark spots appear lighter when the old skin sloths off to reveal new skin with fewer melanin.  This process may take weeks to months and some treatments couple it with chemical peels in an attempt to accelerate the exfoliation process. This effect of lightened skin is temporary so when you discontinue the use of hydroquinone, the dark spots will return.  Immediate side effects of hydroquinone include [1]:

  • Irritation
  • Allergic contact dermatitis
  • Erythema (redness)
  • Inflammation
  • Xeroderma
  • Stinging  
  • Photosensitivity (sun sensitivity)

Long-term side effects are much more serious as we discuss below.  Ironically, those with dark skin have a higher chance of getting these any of these side effects.


Long Term Side Effects of Hydroquinone

Skin Resistance to Hydroquinone: The human body is very adaptive and typically builds a tolerance against foreign threats.  With prolonged use of hydroquinone, in some cases, the skin builds a resistance to the hydroquinone and renders it’s bleaching power useless.  Typically, some people using 4% hydroquinone may experience improvements in the first few months and then notice the improvement stops. In some cases, the hydroquinone causes further lightening to the non-affected areas whereas the melasma areas become resistant, worsening the results of the hyperpigmentation. 

Photosensitivity & Ochronosis: Some may consider ochronosis as the worst type of skin hyperpigmentation because it is difficult to treat with limited success.  Ochronosis, a condition in which the skin appears black-blue due to the accumulation of homogentisic acid in connective tissues. Use of hydroquinone creates photosensitivity due to reduced melanin.  Exposure to the sun can trigger production of the bluish melanin compound that’s responsible for ochronosis. The medical community once believed ochronosis was exclusively among dark-skinned African individuals. However, recently published reports show that the condition is also seen in many fair-skinned individuals such as Europeans, Hispanics and Asians, many of whom have had prolonged use of hydroquinone at concentration 2% or above.[2,3]  According to Dr. Prachi Bhattar from the Department of Dermatology at Patil Hospital and Research Institute, “Hydroquinone containing topical depigmenting agents is the leading cause of EO, especially when used for longer duration.” Doctor Arielle Nagler from New York University School of Medicine warns, “Although the incidence of exogenous ochronosis in the United States is unclear, it may be more common than many clinicians believe.”


What does ochronosis look like? 

Ochronosis cases caused by use of hydroquinone are being documented by doctors to use as an educational tool.  All the cases below have several things in common:

  1. Patients with Fitzpatrick Skin Type III and above

  2. Long-term use of hydroquinone 2% or higher 

  3. Have seeked treatment from doctors without success

CASE 01: Presented by Dr. Nagler and team in 2014.

Female, age 53, Fitzpatrick skin type IV. The patient states that she had normal skin coloring until she underwent an unknown laser treatment to improve her complexion. The procedure left dark pigmentation on cheeks, which displeased her. She returned to the same spa and received hydroquinone cream to apply to her face as a bleaching cream. She initially saw appreciable improvement with the topical hydroquinone treatment. However, after using the topical hydroquinone cream for several years, she slowly noticed darkening of her skin despite continued use of the hydroquinone cream. [4]


Case 02: Presented by Dr, Ribasl and team.

Female patient, aged 36, Fritzpatrick skin type III.  The patient had facial melasma for more than 8 years with gestation of ochronosis.  Dermatologic examination showed brownish macula on the malar region, bilateral, symmetrical, on the dorsum of the nose and supralabial. The patient had been treating with 2% hydroquinone for 5 years and reports progressive hyperpigmentation on the face for 4 years. [5]



Case 03:  Presented by Dr, Ribasl and team. 

Female patient, aged 38, Fitzpatrick skin type III.  Patient has facial melasma for 5 years, presenting brownish macula on the malar and lateral region of the face, symmetrical and bilateral. The patient reported she had been using a facial cream containing hydroquinone in concentrations varying from 2 to 4% for 3 years. She experienced partial response to hydroquinone with frequent relapses without the use of the the clarifying formula. In the last 6 months she reported worsening of hyperpigmentation even though she was still in treatment.[5]

Cancer Controversy

It has been a global debate on the cancer risk of hydroquinone based on a study on the effects of hydroquinone administered orally to rats.  Although there is no conclusive evidence to link cancer to hydroquinone, new research is being conducted to advance our knowledge. We do know that topically applied hydroquinone is absorbed in the body quite well - about 35% to 45% of hydroquinone is absorbed systemically.  Even doctors who advocate for continued use of hydroquinone do not recommend its use during pregnancy and nursing. [6]

According to Dr. Francisco Enguita from the Institute of Molecular Medicine at the University of Lisbon, Portugal, “Recent pieces of evidence showed that hydroquinone is able to enhance carcinogenic risk by generating DNA damage and also to compromise the general immune responses which may contribute to the impaired triggering of the host immune reaction.” [7]

Hydroquinone is currently classified in the European Union, Japan, and Australia as a harmful carcinogen and mutagen and is banned for over-the-counter use.  In the United States, the FDA revoked its previous approval of hydroquinone and proposed a ban on all over-the-counter preparations in 2006. The final decision is still pending and many groups and companies have provided their recommendation.  In the meantime, hydroquinone is available in the US at 2% concentration as over-the-counter and at higher concentrations 4% and above with a prescription and under doctor supervision. 

Pulse Use of Hydroquinone to Reduce Risk

But continued use of hydroquinone introduces other complexities.  Dr. Zein Obagi, a dermatologist in Beverly Hills, CA, who has been a staunch advocate for the use of hydroquinone recognizes the long term risks and has recommended pulsing the use of hydroquinone under strict medical supervision.  According to Dr. Obagi, “To avoid such problems, I recommend that after no more than five months of hydroquinone application, all patients should cease using this drug for two to three months. This allows melanocytes to stabilize (so they can withstand external and internal factors that might otherwise increase their activity) and restore the skin’s natural melanin. During this phase, patients can use other lightening agents, then resume hydroquinone if necessary afterward.” [8]

The trend of super high concentration of Hydroquinone

Now you see ads everywhere for personalized compounded formulas prescribed by a telemed doctor for 12% hydroquinone.  You will read reviews of consumers excited about seeing results at these high concentrations and advocating for the approach.  However, high concentration isn’t better and runs the risk of accelerating photosensitivity and phototoxicity. According to Dr. Obagi, “Based on my observations and experience, such concentrations deliver no greater or faster results than hydroquinone 4%. On the contrary, concentrations of 6-12% tend to cause more recalcitrant hyperpigmentation, quicker resistance, and a higher rate of ochronosis.”  He continues, “However, in the last few years, I have observed a higher incidence of ochronosis not only in African-Americans, but also in Caucasian, Asian, and Hispanic patients who have used various concentrations of hydroquinone, often for years on end. In these patients, ochronosis has occurred in the areas of the face that experience the most sun exposure.”[8]


What are the safer alternatives?

Since 1989, hydroquinone has been shown reproducibly to induce benign neoplasms in the kidneys of male F344 rats dosed orally either by gavage (25 and 50 mg/kg body weight) or diet (0.8%).  Doubt about hydroquinone’s safety encouraged research to find safer alternatives. In general, side effects are less of a concern for these alternative ingredients and combining different whitening agents results in a more potent product without too much irritation.[9]

  • Azelaic Acid
  • Dong Quai
  • Licorice plant extract
  • Soy Proteins
  • N-Acetylglucosamine
  • Niacinamide
  • Vitamin E
  • Turmeric


Alternatives with Some Risks

  • Mequinol is the main alternative prescription alternative to hydroquinone. It is also known as methoxyphenol, hydroquinone monomethyl ether, and p-hydroxyanisole. It can be less irritating than hydroquinone but can cause temporary postinflammatory hyperpigmentation. There have been instances of reversible depigmentation.[9]
  • Arbutin is sometimes known as “natural hydroquinone” since its structure is very similar to that of hydroquinone. Once absorbed into the skin, it gets converted into hydroquinone.  
  • Kojic acid is produced by bacteria in the fermentation of rice in the manufacture of sake (Japanese wine). It is very irritating, therefore is often used in combination with a corticosteroid to reduce the probability of irritation.  Other side effects include redness and inflammation.


Product Recommendation

LeCerre Skincare develops modern innovative skincare for ethnic skin.  It focuses on hyperpigmentation because it is the number one issue among those with skin of color.  LeCerre does not use hydroquinone, kojic acid, arbutin or ingredients that have had clinical studies to show adverse effects of post inflammatory hyperpigmentation.  It’s Rapid Brightening Serum combines 5 active ingredients that have been clinically proven to be effective in reducing dark marks and be healthy for the skin. Because the Serum is so gentle and safe, it can be used by those who are pregnant or nursing.  Many have reported great results with its use.  Read more about their results.

Additional Resources:


[2] Kramer KE, Lopez A, Stefanato CM, Phillips TJ. Exogenous ochronosis. J Am Acad Dermatol. 2000;42(5 Pt 2):869–71. [PubMed] [Google Scholar]

[3] Gil I, Segura S, Martínez-Escala E, Lloreta J, Puig S, Vélez M, et al. Dermoscopic and reflectance confocal microscopic features of exogenous ochronosis. Arch Dermatol. 2010;146:1021–5. [PubMed] [Google Scholar]

[4] Arielle Nagler MD, Christopher S. Hale MD, Shane A. Meehan MD, and Marie Leger MD PhD. Dermatology Online Journal 20 (12): 5 New York University School of Medicine

[5] Jonas RibasI; Antonio Pedro Mendes SchettiniII; Melissa de Sousa Melo CavalcanteIII. An. Bras. Dermatol. vol.85 no.5 Rio de Janeiro Sept./Oct. 2010

[6] Bozzo P, Chua-Gocheco A, Einarson A. Safety of skin care products during pregnancy. Can Fam Physician. 2011 Jun;57(6):665-7.

[7] Enguita FJ, Leitão AL. Hydroquinone: environmental pollution, toxicity, and microbial answers. Biomed Res Int. 2013;2013:542168.