Background: HQ or hydroquinone is one of the most powerful pigment inhibitors used for melasma. It packs a ton of power, but also a sh*t load of side effects & problems including rebound, allergies, skin irritation, darkening of the skin & more.
The cancer risks
Hydroquinone has been studied for potential links to cancer, but evidence is inconclusive, and findings are nuanced. In some animal studies, high doses of hydroquinone led to cancer in rodents, specifically kidney & liver tumors, which raised concerns about its safety. However, these studies used concentrations much higher than what is typically applied in human skin treatments. Read more to understand.
What about the risk for skin cancer with the use of hydroquinone?
Skin cancer risks with hydroquinone are speculative at best. While hydroquinone has not been definitively shown to cause skin cancer in humans, there are some concerns based on animal studies and its classification by regulatory bodies, acknowledging that rats don’t use sunscreen.
The speculation was based upon a 1974 paper suggesting that hydroquinone reduces melanin production. Melanin is the skin’s natural way of protecting against UVB & UVA radiation, which in turn can give rise to skin cancer. Two points I will make-
- The reduction of melanin is not absolute. Hydroquinone reduces melanin formation & does not eliminate it.
- The argument is mute in the context of UV (& visible light) protection because melasma patients are shielded from radiation via avoidance of sun exposure & the use of sunscreen twice daily regardless of sun exposure. If you have not started on sunscreens, you are reading the wrong page. That’s first base.
What brands of hydroquinone should I use?
In Australia the only brand that you can get over-the-counter is Superfade. This contains 2% hydroquinone plus salicylic acid. In the US, you can get Obagi, up to 4% Hydroquinone, whilst in the Wild West of India & some Asian countries, you can illegally obtain HQ of up to, and often beyond 6-8%.
You should seek advice from your dermatologist as to the concentration of HQ to use for your pattern of pigmentation.
What are other hydroquinone substitutes or alternatives?
Several hydroquinone substitutes can help reduce hyperpigmentation & melasma with lower irritation and potentially better safety profiles. Your ideal formulation can be prescribed by your dermatologist, & goes something like this-
Arbutin: A natural derivative of hydroquinone, arbutin is found in bearberry, cranberry, and blueberry extracts. It gradually releases hydroquinone in small amounts, which can reduce pigmentation without the intensity of hydroquinone itself, acknowledging that a small amount is converted to HQ (overrated).
Vitamin C: As an antioxidant, vitamin C (ascorbic acid) reduces melanin synthesis and provides additional benefits by protecting against UV-induced pigmentation and improving skin texture and tone. Vitamin C is often mixed with hydroquinone to stabilize the mix.
Azelaic Acid: Known for its anti-inflammatory properties, azelaic acid is particularly effective for treating melasma and post-inflammatory hyperpigmentation (PIH) with minimal irritation, making it suitable for sensitive skin. Great in pregnancy, it has an awesome safety profile.
Licorice Extract: Contains glabridin, which inhibits tyrosinase and reduces pigmentation. It also offers anti-inflammatory benefits, helping to soothe the skin while lightening dark spots. Licorice is overrated, it resonates with greenies.
Kojic Acid: Derived from fungi, kojic acid is a gentle skin-brightening ingredient that inhibits tyrosinase, an enzyme essential for melanin production. It is often found in combination with other brightening ingredients.
Niacinamide (Vitamin B3): This anti-inflammatory agent reduces pigment production and improves the skin barrier, which can help in reducing dark spots and overall skin brightening. Again, awesome in pregnancy.
Thiamidol: Developed for reducing hyperpigmentation, thiamidol is backed by studies showing it to be comparable in effectiveness to hydroquinone but with fewer side effects, making it a promising alternative . It’s relatively new, so I don’t have an opinion yet, give me 12 months.
Is hydroquinone safe in pregnancy?
Hydroquinone is generally not recommended for use during pregnancy due to a lack of definitive safety data and concerns over its absorption rate. Studies show that hydroquinone is absorbed through the skin which is higher than many other topical treatments, potentially leading to higher systemic exposure. This level of absorption has raised concerns about potential risks to the fetus, even though there’s no direct evidence linking hydroquinone to congenital abnormalities or harm in human pregnancies.
Use these pigment correctors instead; azelaic acid, arbutin, ascorbic acid, kojic acid, botanicals, & niacinamide. More on how to treat melasma in pregnancy.
What are the most common side effects of hydroquinone?
The use of hydroquinone, particularly over long periods, can lead to a variety of side effects, ranging from mild skin reactions to more serious conditions:
Skin Irritation: Commonly, hydroquinone can cause redness, dryness, stinging, or peeling. These symptoms are typically mild but can worsen with increased concentration and duration of use. It is not ‘if’ it causes skin irritation, it is when. Everyone has a different reaction & skin sensitivity.
Allergic Reactions: Some users may experience itchiness, burning, or hives. This can be indicative of an allergic response, and discontinuation is generally recommended in these cases. It is extremely rare, as compared to skin irritation.
Exogenous Ochronosis: A rare but severe side effect, exogenous ochronosis is a bluish-black pigmentation that occurs after long-term or high-dose use. This side effect is difficult to treat and often permanent. Our most feared complication, prevented by listening to your dermatologist.
Rebound Hyperpigmentation: After discontinuing hydroquinone, some users may experience a return of hyperpigmentation that can be darker than the original pigmentation.
What is the most feared side effect of hydroquinone?
Google ‘researchers’ & keyboard Reddit – Facebook experts will place the cancer risks of hydroquinone as a big deal, however most dermatologists, including myself, fear the most serious side effect called exogenous ochronosis. If you develop this, it’s a frigging long & expensive road to recovery as it can take 2-4 years to resolve. In some cases it is permanent.
Ochronosis is a rare but serious skin condition characterized by blue-black pigmentation that develops after prolonged use of hydroquinone, often for skin-lightening purposes. This side effect is primarily associated with higher concentrations of hydroquinone (usually above 2%) and extended use, often several months or years.
In exogenous ochronosis, the skin accumulates pigment deposits within the dermis, which gives it a dark, blotchy appearance that can be more difficult to treat than the original pigmentation issue. The mechanism behind ochronosis is not entirely clear, but it is believed that hydroquinone may alter the skin’s normal pigment formation processes or cause deposits of a pigment similar to melanin.
How long does hydroquinone keep for?
The shelf life of hydroquinone in a container depends on factors like packaging, concentration, and storage conditions. Unopened hydroquinone products are stable for around 1-2 years, even though the expiration date is 2-3 months. Once opened, hydroquinone products typically remain effective for 3-6 months, but their potency can decrease if exposed to air, light, or heat, as hydroquinone is prone to oxidation. Proper storage, like keeping the product in a cool, dark place and tightly sealed, can help maintain its efficacy. You can check if hydroquinone has degraded by looking for any color changes; it may turn brownish if oxidized.
Summary;
- Store in a dark place
- Ignore the expiration date, go by the color of the compound
- If brown, it has expired
Is hydroquinone essential for treating melasma?
Nope, however HQ does play a role in the melasma treatment algorithm. Treatment success is only a number expressed as a percentage chance of me (& the Melasma Clinic team) sorting out your pigmentation. This percentage ranges between 50 to 85%, depending on the level of melasma pigmentation, genetics, radiation exposure (& your understanding of photoprotection) as well as treatment methods.
Does Superfade cause cancer?
No, Superfade has only 2% hydroquinone (very low amounts). You may be concerned if you break into the Superfade factory & ingest 455 tubes of Superfade. That’s a different story.
What do the cancer studies on hydroquinone show (in depth)?
This toxicology study on hydroquinone examined its effects in rats and mice over short (14-day and 13-week) and long-term (2-year) periods. In these studies, hydroquinone was given to rats and mice at various doses, and its impacts were monitored. Key findings included:
Toxicity in Short-Term Studies: In 14-day and 13-week tests, hydroquinone caused toxicity mainly in the liver, central nervous system, and stomach in both species, while kidney issues were noted specifically in rats.
Long-Term Effects: In the 2-year study, lower body weights were observed in high-dose male rats and mice, and severe kidney changes (hyperplasia and cysts) were found in male rats. Both male and female rats developed kidney issues, with male rats showing increased incidences of kidney cell adenomas (benign tumors). Female rats also showed increased rates of leukemia, and dosed female mice had higher occurrences of liver tumors. Thyroid changes were found in both male and female mice.
Evidence of Carcinogenicity. Carcinogenic effects were present in male rats (kidney adenomas), female rats (leukemia), and female mice (liver tumors). However, no carcinogenic effects were noted in male mice.
This study provides evidence that prolonged exposure to massive doses of hydroquinone (0.8% of body weight ingestion) can lead to certain cancers in specific animal models, though similar effects in humans remain unclear. More on this 1992 study here.
What is the link between hydroquinone & leukemia?
High levels of phenol and hydroquinone, which are commonly found in most people’s blood and urine, have been linked to an increased risk of leukemia, particularly in relation to benzene exposure. These compounds can mimic benzene’s toxic effects on blood cells, damage DNA and chromosomes, inhibit the enzyme topoisomerase II, and disrupt blood cell production processes, all of which are associated with leukemia development. Sources of phenol and hydroquinone include certain foods, bacterial metabolism in the gut, tobacco use, and some medications.
This study proposes that these background levels of phenol & hydroquinone may contribute to some cases of leukemia, even among individuals without obvious risk factors like benzene exposure or a smoking history. Genetic factors, diet, medication use, and gut flora composition may all influence susceptibility to leukemia. For prevention, the researchers suggest dietary modifications and reduced use of medications that elevate phenol levels as potential strategies to lower leukemia risk.
More on this paper here.
What study contradicts the cancer risk of hydroquinone to actually reduce cancer?
A recent study in 2018 conversely shows that hydroquinone reduces cancer risk (of specific tumor types). This study investigated hydroquinone (HQ) for potential anti-cancer effects in both cell cultures and animal models. Known for its antioxidant, neuroprotective, immunomodulatory, and anti-inflammatory properties, HQ was tested for its effect on various cancer cell lines, including A431, SYF, B16F10, and MDA-MB-231, where it induced cell death. HQ also enhanced cell death when combined with certain anti-cancer agents, such as adenosine-2′,3′-dialdehyde and buthionine sulfoximine.
In animal models, HQ inhibited angiogenesis in fertilized chicken embryos and reduced lung metastasis of melanoma cells in mice without evident toxicity. Additionally, HQ helped suppress colon cancer development and reduced colon tissue thickness in mice treated with azoxymethane/dextran sodium sulfate. These findings suggest that HQ has significant anti-cancer properties, supporting its potential as a safe and effective anti-cancer treatment.
More on this study here.
What are the real risks of cancer from hydroquinone & what do I recommend?
Dr Davin Lim, Dermatologist | Sydney
The risks of cancer from hydroquinone can be substantiated if-
- You are a rat.
- If you eat copious amounts of hydroquinone.
In the context of topical hydroquinone use, my team & I are far more concerned about side effects such as exogenous ochronosis or pigment darkening with prolonged use.
At the end of the day, the rate limiting factor for HQ use is not cancer, it is the IQ of the end user.
