Melasma is a serious ordeal for the patient and a true challenge for the skincare practitioner. Symmetrical brown patches on the face that fade only to return with renewed intensity after the first sunny day significantly impact patients' quality of life and self-esteem [2]. Why is it so difficult to treat?

The reality is that under the microscope, melasma looks much more complex than a simple accumulation of pigment. Scientists have discovered not only hyperactive melanocytes in the affected areas but also signs of deep dermal photodamage, basement membrane thinning, and, crucially, an abnormal number of vessels and mast cells [2, 3]. Essentially, melasma results from a "miscommunication" among skin cells, blood vessels, and the local immune system. If we try to "bleach out" the pigment while ignoring the vascular and inflammatory components, lasting results will remain elusive [4].

In this context, tranexamic acid (TXA) appears to be an almost ideal candidate for therapy. It is a synthetic lysine analog that has been used in medicine for decades to stop bleeding — primarily as injections during surgeries and trauma or in tablet form for conditions requiring fibrinolysis control. Its mechanism of action involves blocking the conversion of plasminogen to plasmin.

As it turns out, this same process is critically important for the skin. In response to ultraviolet radiation, plasmin activity sharply increases in keratinocytes (epidermal cells). This triggers a cascade of reactions: arachidonic acid is released, and prostaglandins are produced, which force melanocytes to produce excess pigment [1]. By blocking plasminogen activation directly in the epidermis, TXA "cuts off" this pathway and halts UV-induced melanogenesis [1, 5]. Additionally, it can "calm" the excessive vascular network and normalize the local immune status by reducing mast cell activity and inflammatory mediator levels. Thus, TXA targets all key links in melasma pathogenesis—pigmentary, vascular, and immune.

But what is the best way to use it? Oral administration promises a powerful systemic effect but raises concerns regarding its impact on blood clotting. Topical forms seem safer, but can they work just as effectively? To provide clarity, a group of researchers from Iran conducted a direct comparison of these two methods [1].

Study design

The randomized clinical trial involved 50 women with melasma (Fitzpatrick skin types III or IV) who had been unsuccessfully treated for more than six months. They were divided into two groups: the first received oral TXA (250 mg twice daily), and the second applied 5% TXA cream to the face twice daily—a vital condition: both groups used SPF 60 sunscreen every three hours. No decorative cosmetics or other brightening procedures were allowed during the experiment.

A dermatologist monitored the skin condition and assessed melasma severity using the MASI index (area, darkness, and patch homogeneity) at baseline and after 12 weeks. Side effects were also recorded every two weeks.

Results

Forty-nine patients completed the 12-week course. The results were comparable: the "tablet" group saw an average MASI reduction of 58.86%, while the "cream" group saw a 50.88% reduction [1]. The statistical difference between these figures was insignificant, confirming that both forms work almost equally effectively. In nearly half of the participants, pigmentation severity decreased by more than half.

No serious safety issues occurred. In the oral group, four women noted minor cycle changes (oligomenorrhea) but completed the course. No dangerous systemic complications, such as thrombosis, were recorded. In the topical group, only one patient withdrew due to skin irritation.

Practical insights for the practitioner

For practicing specialists, the authors' most important observation is that over a 12-week course, oral TXA (250 mg twice daily) and 5% topical TXA (applied twice daily) produce a similar reduction in melasma severity, as measured by MASI [1]. Both regimens showed significant clinical dynamics and acceptable safety, providing grounds to choose the formulation based primarily on the patient's profile and clinical context.

From a practical standpoint, several points can be highlighted:

• Melasma is not just a "pigmentary" issue but also a vascular-inflammatory one. Therefore, therapy should be built around multiple links in the pathogenesis — photoprotection, trigger control, and a rational choice of local and/or systemic agents. Tranexamic acid is particularly interesting as a tool that influences plasmin-mediated and inflammatory mechanisms, indirectly reducing melanogenesis [1, 5].
• Both forms of TXA demonstrate comparable efficacy via MASI after 3 months of therapy. This allows orientation based on individual indications and preferences: the topical form may be especially relevant for patients who are not ready for systemic therapy. In contrast, the oral form can be discussed for more pronounced melasma in the absence of contraindications [1, 5].
• Safety remains a critical aspect when choosing oral TXA. Despite the absence of serious complications in this study, the practitioner needs to consider the patient's overall somatic status and history. Key contraindications for systemic administration include pregnancy, lactation, coagulation disorders, and a high risk of thromboembolism. Caution should also be exercised when prescribing the drug to patients taking oral contraceptives [1]. For the topical form, the main limitations remain the risk of local reactions (irritation, erythema) and the need for strict adherence to the product's shelf life [1].
• The effect should be viewed as part of a comprehensive program. Even with a 50–60% reduction in MASI, melasma remains a chronic condition prone to relapse. Maintenance photoprotection, control of hormonal and medication triggers, and a well-thought-out long-term strategy are just as important as the choice of TXA form [2, 4, 5].

References

1. Heidary B., Habibzadeh Meibodi G.A., Ebrahimzadeh Ardakani M. et al. Randomized clinical trial on the efficacy of oral tranexamic acid versus topical tranexamic acid in the treatment of melasma. J Cosmet Dermatol 2025; 24: e70428. https://doi.org/10.1111/jocd.70428
2. Sarkar R., Arora P., Garg V.K. et al. Melasma update. Indian Dermatol Online J 2014; 5(4): 426–435.
3. Sheth V.M., Pandya A.G. Melasma: a comprehensive update: part II. J Am Acad Dermatol 2011; 65(4): 699–714.
4. Sarkar R., Gokhale N., Godse K. et al. Medical management of melasma: a review with consensus recommendations by the Indian Pigmentary Expert Group. Indian J Dermatol  2017; 62(6): 558–577.
5. Bala H.R., Lee S., Wong C. et al. Oral tranexamic acid for the treatment of melasma: a review. Dermatol Surg 2018; 44(6): 814–825.