Taking the Pulse of Hydroquinone Therapy: A Plea for Caution - Practical Dermatology (2023)

For many consumers, hydroquinone is like an old friend who inexplicably turns on you. They may have used it for years, trusting that their dermatologist—or, frequently, some Internet pharmacy—would never recommend a product that could harm them.

But over time, some of these consumers develop new pigment problems in the areas where they have faithfully applied hydroquinone. The product they bought to lighten sunspots, melasma, or other hyperpigmentation paradoxically leaves them with tough-to-treat issues such as severe rebound hyperpigmentation and ochronosis.

Avoiding such side effects requires a shift in our approach to hydroquinone. Specifically, my research and clinical experience have convinced me that our patients should use hydroquinone for no more than four or five months at a time. Then we must give the skin a break and allow it to stabilize before deciding if another course of hydroquinone is warranted. I call this approach Pulsed Hydroquinone Therapy.

Medical Products Need Medical Supervision

I have always been a strong proponent of hydroquinone. Used in reasonable concentrations, under physician supervision, it is safe and effective for pigment problems ranging from chloasma, melasma and postinflammatory hyperpigmentation (PIH) and to prepare skin for treatment of less common concerns such as nevi of Ota and Huri which require pigment laser.

But over the last several years, the Internet has become inundated with discounted, medical-grade products that companies sell directly to consumers without proper medical supervision or sun protection.

Consumers want to save themselves a consultation fee or doctor visit. I see no problem with buying a simple moisturizer or broad-spectrum sunscreen online. But to continue treatment with hydroquinone (or other medical-grade skin formulations, for that matter) indefinitely, without the oversight and expertise of the dermatologist who originally prescribed it, often creates dermatologic disasters.

Following are the patterns I see increasingly in my clinical practice, and the reasons behind them.

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Resistance. Some people who have been using hydroquinone in proper concentration of 4% (alone or in compounded formulations) find that their skin improves for a few months, and then the improvement stops. In my experience, this is particularly common after four to five months of satisfactory response in patients using hydroquinone for melasma.

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In such cases, the bleaching effects of hydroquinone appear more pronounced in the areas not affected by melasma. Meanwhile, the dark spots of melasma show no further improvement. In fact, as the active melanocytes in the affected areas develop resistance to hydroquinone, the patient’s hyperpigmentation in these areas worsens.

That is what happened to a 58-year-old female patient from India who was diagnosed with melasma at our clinic in 2001 (see above, Patient 1). At that time, she was treated successfully with hydroquinone 4%, and hydroquinone mixed with retinoic acid, followed by a chemical peel to the papillary dermis. A decade later, after having obtained branded hydroquinone 4% and retinoic acid products from the web and the black market, she returned and was diagnosed with rebound severe melasma (epidermal and dermal) that did not respond but worsened by her continuous hydroquinone use.

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.

Some dermatologists may choose to treat resistant melasma by increasing the hydroquinone concentration. Instead, I have found that patients respond well to aggressive application of hydroquinone (4%) plus retinoic acid, combined in equal parts. This combination tends not to bleach the skin, but to accelerate attainment of a more natural and even color tone. Once the skin’s color has evened out after up to five months of treatment, I have my patients discontinue use of this mixture and switch to retinoic acid alone for two to three months; then patients resume hydroquinone application if needed.

Photosensitivity, phototoxicity. We know that certain topical agents, such as retinoids, aminolevulinic acid, and some systemic medications (such as tobramycin/ TCN and hydrochlorothiazide). can increase skin sensitivity to sun exposure. Surprisingly, no one, to my knowledge, has ever considered hydroquinone to be a photosensitizer.

Some patients use hydroquinone indefinitely, thinking it will prevent unwanted pigmentation. But we now know that decreasing the amount of melanin in skin, as hydroquinone does, creates photosensitivity. Without proper sunscreen use (sun protection factor/SPF ≥ 30, frequent reapplication), photosensitivity leads to inflammation, which stimulates melanin production.

The sun can also affect the melanocytes directly, increasing melanin production and possibly leading to rebound pigmentation. Furthermore, phototoxic reactions can trigger a chemically altered bluish melanin compound that’s responsible for ochronosis, which is tough to treat because it involves deep pigmentary changes deep in the dermis associated with altered skin texture.

Physicians used to consider ochronosis as a condition that was limited to certain African tribes, and we believed that it stemmed perhaps partially from genetic causes, partially from prolonged hydroquinone use.

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.

One such patient I saw was a 39-year-old Caucasian female. She had a history of melasma, and underwent the following treatments, prescribed by various dermatologists, in the two years prior to presenting at our clinic with severe ochronosis: three peels consisting of azelaic acid, kojic acid, phytic acid, ascorbic acid, arbutin, and titanium dioxide (Cosmelan, Mesoestetic) in one year; eight intense pulsed light (IPL) treatments; three fractional laser resurfacing (Fraxel, Solta) sessions; six Jessner’s peels; and continuous use of hydroquinone 8% throughout the two years.

This case also serves as a reminder that when treating hyperpigmentation, we should not use exfoliative procedures, chemical peels, laser resurfacing, or other thermal rejuvenating devices as our first step. Rather, I recommend proper skin conditioning—using hydroquinone, hydroquinone plus retinoic acid, alpha hydroxy acids, antioxidants, and any disease-specific agents necessary—for four to six weeks before and after any procedure (once skin healing is complete). This helps to restore normalcy and functionality to the skin, and it improves the results from procedures.

Excessive HQ concentration. I am used to prescribing hydroquinone concentrations of 4%, and I have treated many patients who used high concentrations on their own or under the supervision of other physicians. 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.

Excessive hydroquinone concentrations may induce toxic or shocking effects on melanocytes, forcing them to regroup and increase their melanin production (resulting in rebound hyperpigmentation). Additionally, high concentrations of hydroquinone may provoke skin inflammation. Used on its own, hydroquinone is an inflammatory agent that can cause redness, itching, and allergic reactions. Inflammation leads to melanocyte hyperactivity, which overpowers hydroquinone’s ability to suppress tyrosinase, leading to the rebound hyperpigmentation.

Such was the case with a 66-year-old African-American female with history of melasma who was treated for seven years by other dermatologists (Patient 2). She used hydroquinone 8%, tretinoin (Retin-A, Valeant Dermatology), and desonide cream (Desowen, Galderma) for years. Dissatisfied with the results, she eventually was prescribed hydroquinone 12%, and her dermatologist added topical steroids to her regimen. Ultimately, her worsening condition prompted this dermatologist to refer her to our office, where she was diagnosed with rebound dermal and epidermal hyperpigmentation, ochronosis with severe irritation and sensitivity. We stopped the hydroquinone regimen immediately.

Hydroquinone combination formulations. In this regard, consumers can readily find products that combine hydroquinone with various ingredients such as retinoic acid, glycolic acid, vitamin C, and topical steroids. However, prolonged use of such products can worsen pigmentation and create additional issues. This is especially true of products that combine hydroquinone, retinoic acid, and steroids e.g., Kligman’s formula and the combination of hydroquinone, tretinoin, and fluocinolone acetonide (Triluma, Galderma). I have found that long-term use of such products can lead to skin atrophy, the appearance of telangiectasias, skin sensitivity, and, frequently, more stubborn pigmentation than the patient originally had.

The topical steroids in these formulations aim to suppress inflammation. This is critical because inflammation excites melanocytes, which stimulate melanin production. However, topical steroids only work on pigmentation induced by trauma or disease (PIH). In contrast, we must avoid prescribing topical steroids for patients with pigment problems not caused by inflammation, such as melasma.

Moreover, to avoid disrupting cellular function, these triple-combination products should not be used for longer than five to seven days, in accordance with their instructions. As an alternative, I prefer the combination of hydroquinone and retinoic acid without a steroid. It is safer, yet quite effective when used properly for three to five months with strict sun protection.

Retinoids Require Caution

As with hydroquinone, however, many medical-grade ingredients, such as retinoic acid and other retinoids, if used indefinitely, prove helpful for two or three months but can then cause continuous irritation. This irritation can lead to inflammation and create more damage as the skin builds resistance to the treatment.

The following patients’ experiences are typical in this regard.

Patient 3 (photo previous page), a 59-year-old Hispanic female with a history of melasma, acne, and scarring, was successfully treated in 1990 with topical creams, isotretinoin, and trichloroacetic acid peels. Her maintenance program included hydroquinone 4%and a hydroquinoneretinoic acid combination, as described above. About five years ago, she returned to the clinic with ochronosis, primarily on the left side of her face (because she drives long distances). She is currently being treated for her ochronosis.

Patient 4 (photo previous page) is a 57-year-old African-American female, seen 25 years ago for PIH and melasma. She responded well to a topical medication that included hydroquinone 4%, used daily, and hydroquinone mixed with retinoic acid in the evening. She also had a trichloroacetic acid peel down to the papillary dermis. Subsequently, she did not follow-up with her treatments, but eventually returned many years later. She had been using the hydroquinone medications continuously, and presented with ochronosis. I had her immediately stop the hydroquinone treatment; she did not desire to treat the ochronosis, saying it did not bother her.

Based on such cases, I now view retinoic acid as a tool for general skin repair; beyond that, it is not always an ideal agent. Patients generally find retinoic acid hard to tolerate long-term because the portion of the drug that is not absorbed for skin repair remains on the skin’s surface, which can provoke continuous reactions. Along with irritation, these reactions can include redness, dryness, and exfoliation. For some patients, these continuous reactions can even break down the skin’s barrier function, creating skin sensitivity. These side effects explain why many patients abandon treatment with retinoic acid.

To avoid these problems, I now recommend that patients use retinoic acid for no longer than five months. That is sufficient time to accomplish general skin repair, without risking long-term skin reactions. After five months, I switch my patients to an agent with specific skin repair functions, such as retinol. For normal to dry skin, it improves barrier function while also stimulating and stabilizing the skin. Because retinol is converted intracellularly to retinoic acid, it leaves no free, unused retinoic acid on the skin’s surface to provoke reactions.

All the cases outlined above share key similarities. Although each patient began treatment under a doctor’s care, they later purchased medical-grade hydroquinone, and other medical-grade ingredients, through online and other unauthorized sources selling at deep discounts. The ready availability of these products, often from websites owned by physicians, pharmacies or other retailers, enabled consumers to use these products without physician oversight for more than five years continuously. Accordingly, I oppose selling medical-grade products on the Internet if they are being offered for the purpose of treating skin conditions without medical supervision. I believe the FDA should intervene to halt such practices.

Conversely, I believe that formulations combining hydroquinone with botanical anti-inflammatory agents and antioxidants that can suppress skin inflammation induced by factors such as sun exposure, hormones, and diet are very helpful in treating hyperpigmentation. Even systemic inflammatory agents such as ibuprofen can accelerate a patient’s response to hydroquinone. They do this by arresting or suppressing chronic skin inflammation.

However, in my view, adding vitamin C or glycolic acid to hydroquinone offers no scientifically documented extra benefits. In fact, vitamin C and glycolic acid can irritate the skin, which leads to inflammation and worsening of existing hyperpigmentation (rebound hyperpigmentation).

Pulsed Regimen Reduces Risks

In conclusion, hydroquinone is safe and effective when used as directed by a physician for a wide variety of pigmentation problems. To increase its efficacy and avoid unwanted side effects, dermatologists should consider the following protocol:

  • Prescribe hydroquinone concentrations no higher than 4%.
  • Require patients using hydroquinone to use proper sun protection.
  • Continue prescribing hydroquinone for no more than four to five months.
  • Allow the skin to rest and restore itself for two to three months after hydroquinone therapy.
  • Resume hydroquinone therapy, if needed, only after such a break.

Adopting the pulsed approach will spare our patients from the disfiguring and needless side effects of extended, self-directed use of hydroquinone.

FAQs

Why do you have to take a break from hydroquinone? ›

This medication usually contains hydroquinone, which lightens the skin. However, prolonged use of topical hydroquinone (without any breaks in use) can cause darkening of the skin, known as ochronosis.

How long should you take a break from hydroquinone? ›

Usage Recommendations. Hydroquinone can be used twice daily for up to five months consecutively. After five months, melanocytes should be allowed to stabilize during a two to three month break from hydroquinone.

What is the problem with hydroquinone? ›

Chronic adverse events related to exposure to hydroquinone are of greater concern. These complications include ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration. Ochronosis is the most common chronic complication related to long-term use of hydroquinone.

How long can I safely use hydroquinone? ›

The hydroquinone should be applied twice daily for 2–6 months. If no results are seen after 2 months, it should be discontinued. Therapy beyond 6 months is not expected to yield additional improvement when positive results are seen.

What not to use with hydroquinone? ›

Dr. Turegano and Dr. Chan both agree hydroquinone does not play well with benzoyl peroxide, hydrogen peroxide, or other peroxide products. Not only will pairing them cause irritation and dryness, but it can also temporarily stain your skin.

What happens after you stop using hydroquinone? ›

Hydroquinone may prove beneficial for a maximum of five to six months. Once you stop using it, you may experience irritation on the affected parts of your body. This may lead to inflammation. This inflammation may be dangerous as your skin then begins to build resistance to the treatment after a certain time.

How do I maintain my skin after using hydroquinone? ›

You can use hydroquinone to treat dark spots and create an even skin tone, but follow these tips to add the product to your skincare routine safely:
  1. Use as a spot treatment. ...
  2. Avoid peroxide products. ...
  3. Avoid alpha hydroxy acids. ...
  4. Apply sunscreen. ...
  5. Consider side effects. ...
  6. Stop application after five months.
15 Sept 2021

Is hydroquinone better in morning or night? ›

Apply Hydroquinone in the evening after Retin-A and in the morning for 2 to 6 weeks prior to the procedure. It helps to stop the production of pigment in the skin and will help prevent the skin from hyperpigmentation (darkening of your skin) after the procedure.

Do dark spots come back after hydroquinone? ›

Answer: Dark spots return after stopping hydroquinone

Yes. Unfortunately, after stopping HQ it is not surprising if the dark spots return, particularly if you are exposed to any sunlight.

What hydroquinone does to your face? ›

Hydroquinone is used to lighten the dark patches of skin (also called hyperpigmentation, melasma, "liver spots," "age spots," freckles) caused by pregnancy, birth control pills, hormone medicine, or injury to the skin. This medicine works by blocking the process in the skin that leads to discoloration.

Can hydroquinone make dark spots worse? ›

Hydroquinone may cause local skin irritation, however, and thereby leading to post-inflammatory hyperpigmentation, making the skin pigmentation worse.

How long does it take for hydroquinone to work on dark spots? ›

It can take approximately 4-6 weeks of daily (or even twice daily) hydroquinone application before dark spots will begin to fade. After 8-12 weeks, optimal results should appear and overall skin tone will become more even.

Does hydroquinone damage your skin? ›

FDA has received reports of serious side effects including skin rashes, facial swelling, and ochronosis (discoloration of skin) from the use of skin lightening products containing hydroquinone.

Can I put hydroquinone all over my face? ›

Most people don't need it all over the skin, just in particular areas. You should use it in the areas with hyperpigmentation.” If you tend to be sensitive, he suggests using it on alternating days. When you know that your hydroquinone product works well with your skin, add a glycolic cleanser to your skincare routine.

Does hydroquinone have side effects? ›

Mild burning, stinging, redness, and dryness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly. If your doctor has prescribed this medication, remember that your doctor has judged that the benefit to you is greater than the risk of side effects.

What is a natural alternative to hydroquinone? ›

Other safe, natural alternatives to hydroquinone include brightening ingredients like kojic acid, vitamin C, mushroom, licorice/glycyrrhizin, azelaic acid, and niacinamide (vitamin B3).

What is the best alternative to hydroquinone? ›

Mequinol (4-Hydroxyanisole)

Mequinol is the main alternative prescription alternative to hydroquinone. It's also known as methoxyphenol, hydroquinone monomethyl ether, and p-hydroxyanisole.

How can I lighten my skin without using hydroquinone? ›

Experts Reveal 7 Ways to Lighten Discoloration Without Using Hydroquinone
  1. 1 / 7. Vitamin C. Vitamin C is one of those beauty ingredients that packs a whole lot of punch. ...
  2. 2 / 7. Peels. ...
  3. 3 / 7. Acids. ...
  4. 4 / 7. Retinol and retinoids. ...
  5. 5 / 7. Arbutin. ...
  6. 6 / 7. Niacinamide. ...
  7. 7 / 7. Licorice extract.
8 Feb 2017

Can I stop hydroquinone abruptly? ›

It is extremely important to not abruptly stop using hydroquinone. This can cause the melanocytes to react poorly and cause rebound hyperpigmentation. Overuse of hydroquinone (at excessive strengths and/or used indefinitely) can also cause an irreversible condition called ochronosis, a bluish discoloration of the skin.

Does hydroquinone get into bloodstream? ›

These experiments showed that hydroquinone was effectively (45% of total dose) and quickly absorbed by the skin (35% of total dose in 1 h) and relatively quickly absorbed into the bloodstream (30% within 1 h).

Will hydroquinone fade age spots? ›

Age spot treatments include: Medications. Applying prescription bleaching creams (hydroquinone) alone or with retinoids (tretinoin) and a mild steroid might gradually fade the spots over several months. The treatments might cause temporary itching, redness, burning or dryness.

How long does it take for hydroquinone to lighten skin? ›

On average, it takes four to eight weeks for hydroquinone to produce noticeable skin lightening results, meaning you'll need to apply it consistently before your melasma-affected skin begins to lighten and match the rest of your face.

Is skin peeling normal with hydroquinone? ›

Skin irritation is one of the most commonly-reported side effects of using topical Hydroquinone. It's been reported that up to 70% of people using Hydroquinone may experience redness, peeling, or dry skin.

Do dermatologists recommend hydroquinone? ›

Hydroquinone is considered the topical gold standard in dermatology for reducing hyperpigmentation.” Dermatologists often use hydroquinone to treat melasma, a skin condition where dark patches appear on the forehead, cheeks and upper lip.

Which foods contain hydroquinone? ›

A previous study reported that hydroquinone was present not only in coffee, but also in tea, red wine, wheat, and fruits.

Do you apply vitamin C before or after hydroquinone? ›

Vitamin C goes first, followed by hydroquinone if the former is in serum and the latter in a moisturizer. It's important to let your skin dry after using vitamin C serum and before hydroquinone cream.

Does hydroquinone make you look younger? ›

Fade Age Spots With Hydroquinone

It interferes with the skin's production of melanin, the pigment that gives age spots their color. Hydroquinone is available over the counter or in stronger concentrations by prescription.

How do you cycle off hydroquinone? ›

Weaning Off Hydroquinone

2 days using the Hydroquinone products, the remainder of the week use Non-Hydroquinone products. 1 day using the Hydroquinone products, the remainder of the week use Non-Hydroquinone products. You should now be only using Non-Hydroquinone products for three months.

Does hydroquinone cause skin thinning? ›

Does hydroquinone thin the skin layer? Hydroquinone itself does not lead to skin thinning. However, multiple studies have found that it achieves optimal results when combined with retinoids and topical steroids.

How can I remove spots from my face in 2 days naturally? ›

Step 1: Mix a teaspoon of turmeric powder, with 1-2 teaspoons of honey, and 1 teaspoon of coconut oil until it forms a paste with a consistency that's not too thick, or too liquid-y. Step 2: Leave it on your face for 20 minutes, and rinse it off with water.

Why is my skin darker after using hydroquinone? ›

In fact, the darkening of the skin from using Hydroquinone can occur because this compound can't really get rid of it, it only inhibits the production of melanin pigment in the skin. When melanocytes die, their accumulation on the skin is inevitable (like any other dead skin cells).

Does hydroquinone affect permanent? ›

Hydroquinone works by suppressing the production of melanin, the brown or black substance that regulates skin pigmentation. Over time, blemishes, scars, or other colored areas fade. However, the effect is reversible; stopping treatment and exposure to sunlight can reverse the condition.

Is hydroquinone cancerous? ›

FRIDAY, May 27, 2022 (HealthDay News) -- Hydroquinone use increases the risk for both melanoma and nonmelanoma skin cancers by more than threefold, according to a study presented at the Society for Investigative Dermatology Annual Meeting, held May 18 to 21 in Portland, Oregon.

Is hydroquinone once a day enough? ›

The lightening effects of prescription strength 4% hydroquinone are achieved with approximately four weeks of consistent, twice daily use. For those with mild hyperpigmentation, using once a day is typically enough to see results.

Does hydroquinone lighten all skin or just dark spots? ›

Christopher Zoumalan, a Beverly Hills-based, board-certified cosmetic surgeon. By halting the skin's production of melanin, hydroquinone prevents existing dark spots from getting darker and causes them to gradually fade. Hydroquinone does not permanently lighten skin.

Can hydroquinone cause depression? ›

The fact that higher doses of hydroquinone are associated with a greater risk of depression is further indication that hydroquinone is responsible for the development of depression.

Does hydroquinone cause liver damage? ›

Apart from its effects on the skin, hydroquinone has been found to expose users to acute toxicity from oral exposure and it can also cause diseases such as thyroid disorder, leukemia, and liver damage.

Does pigmentation come back after stopping hydroquinone? ›

Discontinuation without a proper “weaning” period can lead to rebound pigmentation—pigmentation actually becomes worse and can be further exacerbated by treatment with hydroquinone.

How do you transition off hydroquinone? ›

While transitioning off hydroquinone, continued stimulation with a retinoid is beneficial to prevent rebound pigmentation. Treatment should never stop abruptly! Using a non-hydroquinone tyrosinase inhibiting skin brightener after a hydroquinone cycle can also help enhance results.

How long does it take for hydroquinone to fade dark spots? ›

It can take approximately 4-6 weeks of daily (or even twice daily) hydroquinone application before dark spots will begin to fade. After 8-12 weeks, optimal results should appear and overall skin tone will become more even.

Why do you have to stop hydroquinone after 3 months? ›

It is extremely important to not abruptly stop using hydroquinone. This can cause the melanocytes to react poorly and cause rebound hyperpigmentation. Overuse of hydroquinone (at excessive strengths and/or used indefinitely) can also cause an irreversible condition called ochronosis, a bluish discoloration of the skin.

Does hydroquinone thin your skin? ›

Long-term use can even make the skin thin and fragile. They recommended that people look for a product containing one of the following ingredients: azelaic acid. glycolic acid.

Does hydroquinone cause side effects? ›

Mild burning, stinging, redness, and dryness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly. If your doctor has prescribed this medication, remember that your doctor has judged that the benefit to you is greater than the risk of side effects.

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