Melasma oral and topical medications: is there a difference in effectiveness? Expectations and limitations based on tranexamic acid research

For melasma (light brown symmetrical spots on the cheeks and elsewhere), adding tranexamic acid oral medication to other treatments resulted in greater improvement, as shown in a summary of 28 trials[1]. Topical or injectable tranexamic acid did not show similarly clear differences[1]. Because some people experience recurrence after stopping the medication, this is a treatment requiring a long-term perspective[2].

How effective is tranexamic acid oral medication for melasma?

The oral medication shows clear effectiveness when added to other treatments. In a report summarizing 28 randomized controlled trials (studies comparing treatments assigned by random selection), the group receiving the added oral medication showed greater improvement at 8 and 12 weeks[1].

In a 50-person trial, those who added the oral medication to 4% hydroquinone topical and sunscreen showed a 55% decrease in melasma score over 3 months[3]. Those who added placebo (medication without active ingredients) showed a 10.9% decrease[3].

A separate report summarizing 11 studies with 667 participants also showed further improvement when tranexamic acid was added to routine treatment[4].

Does topical tranexamic acid work as well as oral medication?

Topical or injectable tranexamic acid has not yet yielded clear conclusions. In the summary of 28 trials, the difference when added to other treatments was not clear for either topical or injectable forms[1].

In a 60-woman trial, 5% tranexamic acid topical was compared to 2% hydroquinone topical over 12 weeks[5]. Both reduced melasma scores, with no difference in effectiveness[5]. The hydroquinone group experienced redness or irritation in 10% of participants, while the tranexamic acid group experienced no side effects[5].

What are the roles of hydroquinone and tretinoin?

Hydroquinone is a topical medication often used in combination with other drugs. In actual melasma treatment, combinations with tretinoin, tranexamic acid, laser, and others are more commonly reported than hydroquinone alone[6].

Tretinoin topical accelerates skin renewal and helps expel melanin (the pigment that creates spots) accumulated on the skin surface[6]. The guidelines of the Japan Society of Plastic Surgeons also describe it as effective for melasma and other spots[6].

Hydroquinone may cause irritation, dermatitis, small depigmented spots, and post-inflammatory hyperpigmentation[7]. Long-term use is also known to cause ochronosis (bluish-black discoloration of the skin)[7].

Does melasma return after stopping medication?

Some people experience recurrence after stopping. In a study of 6 months of oral medication use, about 65% of people showed good to very good improvement, but 9.5% experienced recurrence[2].

In a 50-person trial combining hydroquinone with oral medication, 3 months after stopping medication and using only sunscreen, the score remained 42% lower than before treatment[3]. While sunscreen is important, it is often noted that sunscreen alone cannot fully prevent recurrence[1].

What side effects should I watch for?

Most side effects of oral medication are mild. Stomach discomfort and reduced menstrual flow have been reported[4][2].

Tranexamic acid is originally a medication to stop bleeding. The dose used for melasma is said to be much lower than the dose used to stop bleeding[1]. Tell your doctor about any chronic conditions, medications you are taking, and plans for pregnancy before starting

How do I choose between oral and topical medication?

When the research results are arranged by medication, they are as follows.

Tranexamic acid oral medication: many reports show greater improvement when added to other treatments[1][3]

Tranexamic acid topical: less irritating, but the difference in effectiveness is still not clear[1][5]

Hydroquinone: often used in combination, with attention to irritation[6][7]

Tretinoin: accelerates skin renewal and is considered effective for melasma[6]

Whether your spots are truly melasma cannot be determined from an article alone. During examination, have the type of spots identified, report any chronic conditions, menstrual history, and pregnancy plans, then confirm whether oral medication can be used and which topical medication to combine