Should You Use Oral Or Topical Treatments For Hyperpigmentation?

Should You Use Oral Or Topical Treatments For Hyperpigmentation?

As you explore possible treatments to address unwanted dark spots on your skin, you may be wondering whether oral or topical treatments for hyperpigmentation would be more effective. Keep reading to learn about the benefits and drawbacks of each, and tips to determine which one is best for you.

Topical treatments for hyperpigmentation

Most topical treatments for hyperpigmentation function by reducing the production of melanin, a biological pigment, in treatment areas. This is accomplished by both preventing the production and promoting the breakdown of melanocytes, cells that produce melanin to protect the skin from UV damage.

Some of the most common topical treatments for hyperpigmentation include:

  • Hydroquinone, considered the “gold standard” lightening agent for hyperpigmentation and melasma worldwide
  • Retinoids, a derivative of Vitamin A used to treat acne and combat aging and sun damage that helps hydroquinone work more effectively
  • Steroids which help reduce the likelihood of skin irritation in combination therapies

Topical treatments are often comprised of a combination of these ingredients. Retinoids help hydroquinone to be more effective, while steroids reduce the likelihood of skin irritation. Studies indicate that combination therapy with 4% hydroquinone, tretinoin (a retinoid), and a steroid are the most effective combination of this type (Grimes). Typical side effects of hydroquinone and other topical treatments are typically mild if used as prescribed.

In September 2020, the CARES Act required retailers to pull hydroquinone products from shelves due to concerns about its misuse. Previously, hydroquinone products were available over-the-counter in percentages of 2% or less. However, misuse of hydroquinone as an all-over skin lightening treatment can result in conditions like ochronosis, which can result in more noticeable dark spots which are resistant to treatment (Faridi).

Oral treatments for hyperpigmentation

Traditionally, treatment for melasma or hyperpigmentation has taken the form of topical agents. However, in recent years, studies have explored oral therapies to address skincare concerns resulting in dark spots or patches on skin.


Glutathione is a powerful antioxidant naturally produced by the body that has skin lightening effects. It is the most common oral lightening treatment for the skin. A study showed at least moderate lightening in 90% of subjects (Grimes). However, intravenous use of glutathione that is not in line with medical recommendations can result in potentially fatal conditions like anaphylaxis or Stevens-Johnson syndrome.

Tranexamic acid

Tranexamic acid is a synthetic version of the amino acid lysine. It is typically used to treat heavy menstrual bleeding that also has lightening effects. Studies show an improvement rate of up to 90% in treatment of melasma (Grimes). It achieves this by interfering with the production of melanin.

Because tranexamic acid promotes blood clotting, people with heart conditions or blood disorders should make sure to discuss this with their doctor before taking tranexamic acid due to a risk of thrombosis. People who have issues related to color vision should also speak to their doctor.


Melatonin is a natural hormone and powerful antioxidant. A study revealed that when used in combination with topical hydroquinone formulas, all patients showed significant reduction in the appearance of melasma (Grimes).

Things to consider when choosing oral or topical treatments for hyperpigmentation

There are other factors to consider beyond ingredients to determine which treatment method would work best for you, including:

  • Your existing routine: Treatments work best when they are used consistently. If you already take oral medications on a daily basis, then simply adding another one is more likely to result in more consistent treatment. Conversely, if you already have an established skincare routine, using topical treatments daily may result in more success.
  • Lifestyle changes: Excessive sun exposure often triggers melasma or hyperpigmentation, as the skin produces melanin to protect itself from UV damage. Just one day of overexposure can result in the loss of progress in treatment and reappearance of dark spots. Ensuring you use sunscreen, wearing protective clothing, and avoiding direct sun exposure during peak hours can make a big difference in your progress.


Custom Oral And Topical Hyperpigmentation Treatments From ClearifiRx

ClearifiRx offers professional dermatology services via our secure health portal, allowing you to get your questions answered from wherever you are. After a consultation to discuss your concerns and goals, our experts will create a custom treatment plan, which will be shipped directly to you.

Your progress will be monitored through our health portal, and if necessary, your prescriptions will be tweaked to achieve the best results possible.


Brandon Kirsch

Brandon Kirsch, MD, FAAD, is a board-certified dermatologist specializing in clinical drug development and medical innovation. He is the founder of Kirsch Dermatology in Naples, Florida and is also the Chief of Dermatology at the Naples Community Hospital. Kirsch Dermatology Website Dr. Kirsch started his career as a lawyer and holds law degrees from the University of Western Ontario (LL.B.) and Georgetown (LL.M. Securities and Financial Regulation). Dr. Kirsch completed his pre-medical studies at the University of Pennsylvania, medical school at Brown University, internship at the Mayo Clinic (Florida) and dermatology residency at the University of North Carolina. In partnership with the Mayo Clinic, he filed to patent a novel topical composition for the treatment of skin hyperpigmentation that he co-developed and also oversaw a successful pilot study of the formulation. Dr. Kirsch has experience with therapeutic drug development programs from pre-clinical to Phase 3 studies. He is licensed to practice medicine in California, Colorado, Florida, and North Carolina and law in New York and Ontario.

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