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Melasma Treatments: Exploring Beyond Hydroquinone Creams for Hyperpigmentation - M

Melasma Treatments: Exploring Beyond Hydroquinone Creams for Hyperpigmentation

Reviewed by Michael Hua, Pharm D
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They say beauty's only skin deep, and the person inside is what really matters. However, when dark spots on the face make you feel less than confident, the problem can have a detrimental effect on your everyday life and emotional well-being. For women who struggle with melasma, dealing with dark patches and spots can involve everything from thick makeup to cover the imperfections to questionable attempts to eradicate or lighten the areas of discoloration.

Melasma, which may also be called chloasma, is a relatively common skin issue that is characterized by hyperpigmentation on the face. The condition can cause dark or discolored spots that look like brown patches on the skin, and these spots don't usually go away fully. Melasma can be chronic, oftentimes even fading and returning in full force over the course of time or with exposure to different agents like heat or light.

Even though men can have issues with melasma, the condition most commonly affects women with 90 percent of cases affecting the female population. Some researchers speculate that melasma affects around six million women in the United States. During pregnancy, the condition is often called the "mask of pregnancy."

The skin discoloration associated with melasma can appear as brown, brownish-gray, or even dark brown or dark black spots on the skin of the face. Most often, the discoloration will be most visible on the:

  • Forehead

  • Cheeks

  • Nose

  • Chin

  • Upper Lip

Some women will also find areas of discoloration on other parts of their body beyond their face, such as on the arms, back, or neck. In general, however, the darkened spots will be most prevalent on areas of the body that are most exposed to the sun.

The skin is a fascinating organ and our first line of defense against many threats in the everyday environment. While your skin may seem like a smile layer of tissue, it is actually made up of an array of complex pathways and cells. Special cells known as melanocytes create melanin using an oxidase enzyme called tyrosinase. Melanin is responsible for generating skin pigmentation, but also protects the skin and tissue from UV radiation from the sun.

While people are born with different levels of melanin that determine general skin color, melanin can actually be generated through a process known as melanogenesis. In short, when the body is exposed to heightened levels of UV light, melanogenesis occurs to further protect the body and prevent injury to the skin. You may have experienced this general process when your skin gets darker or freckled due to more exposure to the sun in the summer. However, in some situations, the over-production of melanin leads to hyperpigmentation like melasma.

While some people will only get a tan or freckles with more exposure to UV rays, others can develop dark patches of melasma, but exactly why this is the case is not entirely known. What we do know is certain people can be more at risk of melasma, such as people with darker skin tones that are of African, Asian, or Hispanic descent. Women between the ages of 20 and 40 are more likely to have problems as well.

A few other risk factors include:

  • Sensitivity to estrogen or progesterone levels

  • Stress

  • Thyroid disease

  • Excessive sun exposure

  • Tanning bed use

  • Phototoxic drugs or drugs that make you more sensitive to the sun

For individuals with sensitivity to estrogen or progesterone, typical things like pregnancy, birth control, or hormone replacement therapy can bring about problems with melasma. In fact, melasma is most associated with certain oral contraceptive use and pregnancy. During pregnancy, as much as 50 percent of women will have problems with skin discoloration that could be diagnosed as melasma.

With excessive sun exposure, skin damage can occur that may be related to melasma. For example, some people may experience a fatty acid deficiency with excessive sun exposure, and this may encourage points of hyperpigmentation. Therefore, people who live in geographic locations with higher levels of UV radiation may have a higher risk of melasma.

It is also worth noting genetics may play a role in melasma. Around 33 to 50 percent of people who are diagnosed with melasma have a relative with the condition. Further, most identical twins will both develop melasma.

Melasma is essentially physically harmless. The skin should not feel any different, itch, burn, or otherwise cause discomfort. Furthermore, people who do develop problems with hyperpigmentation are not usually at heightened risks for skin cancer, even though that is an ongoing myth.

Even though melasma is not considered dangerous or linked to skin cancer, certain types of skin cancer can take on appearances much like melasma. Therefore, any dark spots should be evaluated by a medical professional to rule out any risk that what you have is skin cancer.

Melasma in the past has been notoriously difficult to treat for a few reasons. For one, the skin condition can be chronic but can also have periods of relapse, or times when hyperpigmentation does not show up much at all. For example, a younger female may develop melasma after oral contraceptives that fade with time, but 10 years later, dark spots on the face may re-emerge after spending an excessive amount of time in the sun.

Two, because the precise cause of melasma is not always clear, the typical treatments are generally aimed at using topical agents in an effort to lighten the dark or brown patches.

For quite some time, the most standard way to treat melasma has been hydroquinone creams or other medications that act as tyrosinase inhibitors. When tyrosinase is inhibited, melanin production is slowed, so hyperpigmentation may subside.

Hydroquinone is the most preferred tyrosinase inhibitor recommended, but the drug is commonly formulated with agents that support the actions to target melasma. For example, you may see hydroquinone formulated with hydrocortisone and retinoic acid. You can find most of these whitening cream products available over-the-counter, but higher concentrations do have to be prescribed.

In some studies, 55 percent of participants given topical hydroquinone creams for melasma saw good to excellent improvement. Unfortunately, while hydroquinone was recognized as safe and effective by the Food and Drug Administration in 1982, over-the-counter products were later pulled and the FDA only approved concentrations of 2 percent to deter adverse reactions.

Further, some people have issues with redness or dryness after using hydroquinone, specifically individuals who have more sensitive skin. In rare situations, overuse of hydroquinone can cause papules or black or bluish skin pigmentation known as ochronosis. Therefore, most physicians will only recommend the use of hydroquinone creams for less than five months.

Several up-and-coming agents have been examined for the treatment of melasma, and many are showing better outcomes and safety profiles than the standard hydroquinone whitening cream. Here is a look at three of the most exciting agents

Tranexamic Acid

Tranexamic acid (TA) works by inhibiting melanocyte production thanks to supposed antiplasmin properties. When UV light increases plasmin activity, melanocyte production lowers, which means the TA may deter certain levels of UV damage. In short, the process that takes place when more melanin is produced, melanogenesis, is disrupted with the use of TA.

In one study published in 2014, it was noted that TA seemed to be as effective as hydroquinone in reducing dark spots on the skin. Even better, the group using TA had significantly fewer side effects. In a clinical study of 33 individuals with either melasma or freckles, 80 percent of people with melasma and freckles and 75 percent saw an improvement in freckles. It was also stated that no side effects were noted and improvements were witnessed at eight weeks.

Kojic Acid

Kojic acid (KA) is a natural byproduct that occurs during the fermentation process of certain types of fungi. KA has long been recognized for its ability to whiten dark spots on the skin because it interferes with melanin production. It is thought that KA does so by inhibiting tyrosinase activity.

Even though KA has not been closely examined on its own for melasma, studies have looked at how KA performs in combination with glycolic acid and hydroquinone. In a study published in the Journal of Dermatological Surgery, the combination formulation was tested on 20 women of Chinese descent. Another 20 women of the same descent were given the topical gel without KA. Researchers found that 60 percent of women receiving gel with KA saw improvements, while only 47.5 percent saw improvements without KA.


Niacinamide skin benefits have been pointed out numerous times in medical research for everything from enhancing the lipid barrier to minimizing pore damage and deterring signs of aging. However, this form of vitamin B3 can also help with hyperpigmentation caused by melasma.

In a double-blind, randomized controlled trial published in the journal of Dermatology Research and Practice, good to excellent improvement occurred with dark spots on the skin. While the group of study participants given hydroquinone saw more improvement, niacinamide had a very low side effect profile by comparison. In addition, researchers noted that niacinamide didn't just decrease skin pigmentation, but niacinamide serum also seemed to decrease solar damage and inflammation.

With three promising agents with good safety profiles available, researchers went to work to create a study that combined the benefits of tranexamic and kojic acids combined with niacinamide serum. In the 12-week study, 60 percent of the female study participants had pigmentation improvements, 54 percent had skin tone improvements, and 81 percent even had decreased issues with post-inflammatory hyperpigmentation.

Whether you have mild melasma or a more severe problem, it is well worth looking at the possible melasma treatments available that could improve the appearance of your skin. Some of the latest research has breathed new life into how medical professionals look at the treatment for melasma, and compounded solutions are some of the most modern-preferred options.

If you are interested in trying a compounded topical of niacinamide, kojic acid, and tranexamic acid to reduce dark spots on your skin, reach out to us at Harbor Compounding Pharmacy. While there may be no complete cure for melasma because there is a lot yet to be determined, we have witnessed firsthand how these combination topicals have helped our clients. Contact us today for more information about melasma treatments that may work for you.

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