Melasma is a common hyperpigmentary disorder with a high recurrence rate and inconsistent treatment response, partly due to its pathogenesis not yet being fully understood. This is largely due to the current limited understanding of the pathogenesis of melasma. Epidemiologically, the incidence of melasma varies widely depending on the population and geographical area, ranging from less than 10% to over 40% in some populations - with a significantly higher frequency observed in women of childbearing age and in darker-skinned groups, especially in areas with high UV radiation intensity [7, 15].

In recent years, along with an increased awareness of skin health and aesthetics, melasma has been recognized not merely as an aesthetic problem associated with age or genetics, but as a complex pigmentary disorder with a complicated pathogenesis. This change in approach highlights the need to develop mechanism-based treatments, rather than focusing solely on the end manifestation of increased pigmentation.

Among these, one classic approach is the inhibition of the enzyme tyrosinase – the enzyme that catalyzes key steps and is considered the rate-limiting factor in melanin biosynthesis. However, recent histological and molecular biological data show that melasma is not only a disorder localized to melanocytes, but also involves an abnormal inflammatory and vascular microenvironment in the affected skin, with the involvement of mast cells, vascular endothelial growth factor (VEGF), and paracrine signaling between various cell types. These factors contribute to maintaining melanocyte stimulation and promoting pigment retention or hyperpigmentation [15].

From a modern perspective, the process of pigment formation and maintenance is the result of the interaction of many factors, from external triggers, endocrine and inflammatory signals, melanocyte activity, melanosome synthesis and transfer, to changes in the dermal microenvironment and vascular system. This multi-layered approach also raises an important question: is targeting only one enzyme like tyrosinase sufficient to control the entire pathogenic process and limit the risk of melasma recurrence?

In this context, Tranexamic Acid (TA) – a plasmin inhibitor commonly used in hemostasis – has emerged as a treatment approach with a different mechanism of action compared to classic tyrosinase inhibitors. This article synthesizes existing studies on the epidemiology, pathogenesis, and current treatment methods for melasma; evidence for the role of the inflammatory-vascular axis, especially VEGF, in melasma pathogenesis; and the pharmacological mechanism of TA in treating melasma, including the plasmin-prostaglandin inhibition pathway, direct action on VEGF receptors, and the TGF-β1 pathway. Based on this, the article discusses the place of TA in a multi-mechanism treatment regimen [1, 7, 15].

Abbreviations

1. Overview of Melasma

1.1. Definition and Clinical Characteristics of Melasma

Melasma is a common form of hyperpigmentary disorder, typically manifesting as light to dark brown patches or plaques, symmetrical with irregular borders [6]. Melasma often appears on the forehead, nose, and cheeks or other facial areas directly exposed to sunlight, and can worsen with prolonged exposure. According to reports from many countries, the average age of melasma onset ranges from 20 to 40 years [6]. Although melasma can affect both men and women, many reports show that women are approximately 9-10 times more likely to develop melasma than men [16].

This condition is more prevalent and tends to occur more frequently in individuals with Fitzpatrick skin phototypes III–IV [4]. The incidence of melasma in pregnant women is significantly higher and can reach up to 63% in pregnant women. Pregnancy is the most common risk factor for melasma in women, while in men, the most common risk factors are sun exposure and a family history of melasma (Majid and Aleem, 2021).

Although melasma is a benign skin disorder, if an appropriate, timely, and optimal treatment regimen is not applied, this condition can cause many negative psychological and emotional effects, including feelings of frustration, feeling unattractive, and shame [19].

Figure 1: Distribution patterns of melasma. This diagram illustrates common melasma distribution patterns on the face. Centrofacial pattern (blue): affects the forehead, cheeks, nose, upper lip, and chin, and is the most common presentation. Malar pattern (pink): primarily localized to the cheekbones and nasal bridge. Mandibular pattern (yellow): affects the jawline and chin. Source: BioRender. Rivera, J., Pattern distribution of melasma (2026).

1.2. Research History and Evolution in the Understanding of Melasma

The history of melasma research reflects a significant shift in understanding its nature, risk factors, and pathogenesis. Hyperpigmentation was first noted in 1910. In subsequent years, this facial dark pigmentation was termed chloasma. For a long time, melasma and chloasma were used interchangeably. However, melasma is now the widely accepted term to describe this facial hyperpigmentation with its characteristic symmetrical distribution. In the early stages of research from 1930 to 1990, various hypotheses were proposed to explain the causes and mechanisms of melasma formation.

Although the exact cause of melasma has not been fully determined, current evidence suggests it is a multifactorial condition, with key contributing factors including:

• Genetic predisposition
• Ultraviolet (UV) radiation
• Visible light
• Hormones

Recent studies indicate that heat and visible light can also contribute to pigment changes and trigger melasma flare-ups or recurrences. Advances in histopathology have further transformed the understanding of melasma's pathogenesis. Studies have documented numerous abnormal features in affected skin, including basement membrane changes, increased vascularity, increased mast cells, and general solar elastosis. These findings strengthen the hypothesis that melasma is not merely a disorder of epidermal melanin overproduction but may involve photoaging and alterations in the skin's microenvironment [12].

1.3. Pathogenesis of Melasma

Recent research has elucidated the multifactorial pathogenesis of melasma. Initially, melasma was thought to be confined to melanocytes. However, we now understand that these disturbances extend beyond the interaction between keratinocytes and melanocytes in the skin.

Abnormalities include melanocyte activation, melanin and melanosome accumulation, increased mast cell count, increased vascularization, basement membrane damage, extracellular matrix (ECM) abnormalities, and photoaging, evidenced by solar elastosis in both the dermis and epidermis, as shown in Figure 2 [13].

Figure 2: Diverse physiological and molecular mechanisms of melasma [12]

The complex histological features and clinical manifestations observed in patients suggest the involvement of various pathogenic pathways. Gene expression analysis in lesional skin compared to surrounding skin shows differences in approximately 300 genes, highlighting the complexity of the pathogenesis and etiopathogenesis [14, 18].

1.4. Available Treatment Methods

Current melasma treatments can be categorized by their primary mechanisms of action, including:

• Topical melanin synthesis inhibitors: Hydroquinone, Arbutin, Kojic Acid, Azelaic Acid, Niacinamide - acting mainly through competitive or non-competitive inhibition of tyrosinase enzyme.
• Anti-inflammatory and antioxidant agents: Vitamin C, Vitamin E, Azelaic Acid, some plant extracts.
• Agents affecting skin barrier and epidermal regeneration: Retinoids, Ceramides, and skin barrier repair aids.
• Agents intervening in vascular and inflammatory systems: Tranexamic Acid (oral, topical, or intradermal injection).
• Procedural methods: lasers (including Pico laser, pulsed dye laser), microneedling, chemical peels, often considered in combination with medical treatment in cases of poor response to topical monotherapy.

Despite numerous treatment options, challenges remain, with a high relapse rate observed after treatment cessation. This is partly attributed to the fact that most current treatments primarily focus on inhibiting melanin production – specifically the tyrosinase enzyme – while upstream disease-sustaining factors, particularly inflammatory and vascular components, are not thoroughly addressed in many regimens. This forms the basis for recent research focusing on elucidating the role of the inflammatory-vascular axis in melasma pathogenesis, thereby opening new avenues for supplemental treatments.

2. The Inflammatory-Vascular Pathway in Melasma Pathogenesis

2.1. Histological Evidence

Histologically, melasma is characterized by increased solar elastosis, damage to the epidermal-dermal basement membrane, increased dermal vascularity, mast cell infiltration, and subclinical inflammation, sometimes accompanied by perivascular lympho-histiocytic infiltrates. The basement membrane plays a crucial role in maintaining epidermal-dermal homeostasis, exhibiting structural abnormalities in melasma patients, including fragmentation, thinning, reduced lamina densa density, and loss of anchoring fibrils of the lamina lucida; many basal cells containing pigment and increased melanin are observed protruding into the dermis, suggesting a role for basement membrane damage in melasma pathogenesis. Reflectance confocal microscopy reveals increased solar elastosis and vascularity in the dermis, with moderate mononuclear and mast cell infiltration. The increased presence of mast cells and infiltrating leukocytes in lesional skin is considered a sign of chronic skin inflammation [15]. Quantitatively, an immunohistochemical study using Factor VIIIa-related antigen noted a total increase of 68.75% in the skin area covered by blood vessels in melasma lesions compared to adjacent healthy skin [13].

This is one of the clearest quantitative pieces of evidence demonstrating that angiogenesis is a consistent histological feature of melasma, not a random or insignificant secondary phenomenon.

2.2. Role of Vascular Endothelial Growth Factor (VEGF) and Related Factors in Melasma

Increased vascularity in melasma is observed via dermoscopy and reflectance confocal microscopy, accompanied by a significant increase in VEGF expression in melasma lesions [15]. VEGF is a keratinocyte-derived factor, produced in response to UV radiation, acting through both autocrine and paracrine mechanisms on epidermal cells and dermal tissue by binding to VEGF receptors (VEGFR) [22]. Epidermal keratinocytes have been shown to express VEGFR and co-receptors, and autocrine VEGF/VEGFR-2 signaling has been detected in keratinocytes, with UV radiation capable of activating VEGFR on normal keratinocytes as part of a cell survival mechanism. More importantly, normal human melanocytes also express functional VEGFR, and VEGFR-2 expression is upregulated by UVB radiation, suggesting the ability of melanocytes to directly respond to angiogenic factors [22].

In cell culture studies, VEGF has been shown to maintain human melanocyte activity, and this mechanism is considered one of the factors promoting increased melanocyte activity in melasma [15]. However, not all studies agree on the role of VEGF in melanogenesis in melasma. Kwon et al. (2016) note that while functional VEGF receptors have been identified on melanocytes in vitro, there is still a lack of evidence to suggest that VEGF is a strong melanogenic factor; according to this group of authors, the observed increased vascularity is more likely a consequence of solar elastosis due to chronic UV exposure, and stem cell factor (SCF) – not VEGF – is the potent melanogenic cytokine associated with solar elastosis, thereby enhancing melanogenesis in the overlying epidermis. Following this line of reasoning, increased vascularity is considered a characteristic feature of skin aging, and melasma is proposed as a distinct phenotype of photo-induced damage in the aging process, rather than a simple epidermal pigmentary disorder. This suggests that anti-aging and anti-angiogenic treatments should also be considered in melasma, alongside pigment-targeting treatments [13].

The existence of these two differing viewpoints, VEGF as a melanogenic factor and VEGF as a co-marker of solar elastosis with an unproven melanogenic role, reflects the current reality: the link between vasculature and pigmentation in melasma is relatively well-established at a correlational level, but the detailed causal mechanism, especially the specific role of VEGF compared to other paracrine factors, is still being clarified.

Besides VEGF, several other paracrine pathways originating from vascular endothelial cells have also been implicated in melanogenesis in melasma. Endothelin-1 (EDN1, or ET-1), released by endothelial cells, activates melanogenesis by binding to endothelin receptor type B (EDNRB) and activating MAPK, ERK1/2, and p38 signaling pathways; studies confirm that EDN1-induced melanogenesis occurs via the GPNMB (glycoprotein non-metastatic melanoma protein B) pathway regulated by MITF. Nitric Oxide – in addition to its role in smooth muscle relaxation – also initiates melanogenesis in response to UV radiation, through guanylate cyclase activation, leading to cGMP production and MITF expression; increased inducible nitric oxide synthase (iNOS) expression is observed in melasma lesions, possibly through the Akt/NF-κB pathway, suggesting a significant role for nitric oxide in the hyperpigmentation mechanism of melasma [15].

Furthermore, one study reported significantly increased SCF expression in the dermis and c-kit in the epidermis in lesional skin; another study showed increased dermal c-kit expression compared to perilesional skin, with up to 70% of c-kit-positive basal cells protruding into the dermis, compared to only 29% in perilesional skin. SCF is considered to play an important role in skin pigmentation disorders and is therefore a noteworthy potential therapeutic target [15].

Despite ongoing debate about the precise role of each individual paracrine factor, the available data generally agree on one point: melanocytes in melasma do not operate as an isolated unit but are continuously influenced by a network of paracrine signals originating from keratinocytes, vascular endothelial cells, and mast cells – including VEGF, EDN1, nitric oxide, and the SCF/c-kit axis [13, 15, 22].

This provides a rationale for considering active ingredients that target the inflammatory-vascular axis, in addition to classic tyrosinase inhibitors, as a supplementary treatment approach. It also highlights the need for caution when interpreting the mechanism of any active ingredient acting on a single paracrine factor (such as VEGF) as a complete explanation for the entire vascular component of the disease.

3. Tranexamic Acid in Melasma Treatment

3.1. Definition of the Active Ingredient

Tranexamic Acid (TA) is a synthetic derivative of the amino acid lysine, belonging to the antifibrinolytic class of drugs. Pharmacologically, TA competitively inhibits the binding of plasminogen (and plasmin) to fibrin by binding to the lysine binding sites on the plasminogen molecule, thereby inhibiting the conversion of plasminogen to plasmin and reducing fibrinolysis [9, 11]. TA is widely used in medicine with approved indications such as controlling heavy menstrual bleeding, hemorrhage in trauma and surgery, and preventing bleeding in hemophilia patients [3]. The use of TA in melasma treatment is currently an off-label indication in most countries, although it has been included in some dermatological treatment guidelines in certain regions [11].

3.2. Mechanism of Action in Melasma

Most treatments aim to reduce melanin production (melanogenesis) and the accumulation/invasion of melanin into the dermis. Common first-line treatments for melasma include topical skin-lightening agents such as Hydroquinone (HQ), Azelaic Acid, Mequinol, Kojic Acid, and Retinoids [17]. Other second-line therapies include chemical peels and laser treatments. In practice, dermatologists often use a combination of treatments with varying degrees of effectiveness.

Studies have shown that TA can inhibit melanin formation by suppressing the release of paracrine melanogenic factors that typically stimulate melanocytes; therefore, TA has been extensively studied as a treatment for pigmentation disorders, in addition to its traditional use in treating bleeding disorders. Another effect of TA is to reduce Vascular Endothelial Growth Factor (VEGF) and endothelin-1-induced angiogenesis, thereby reducing the manifestation of hyperpigmentation. TA can be administered orally, intradermally, topically, and transepidermally to treat melasma [11].

3.2.1. The plasmin – prostaglandin – tyrosinase pathway

The earliest and most commonly cited mechanism involves the inhibition of UV-induced plasmin activity in keratinocytes. UV radiation increases plasmin activity in keratinocytes; plasmin then promotes the release of free arachidonic acid from cell membranes, and arachidonic acid is metabolized into prostaglandins – intermediates that stimulate tyrosinase activity. By inhibiting plasminogen binding, TA reduces the amount of free arachidonic acid, thereby indirectly reducing prostaglandin synthesis and tyrosinase activation [11, 21].

3.2.2. Direct effect on VEGF receptors

An in vitro study by Zhu et al. (2020) provided evidence that TA can directly act on VEGF receptors. In this study, VEGF165 was noted to increase the expression of VEGF receptors (VEGFR-1, VEGFR-2, NRP-1) and promote tyrosine phosphorylation of these receptors on human umbilical vein endothelial cells (HUVEC) – both phenomena were diminished in the presence of TA. TA was as effective as direct neutralization of VEGFR-1 and VEGFR-2 in inhibiting VEGF165-induced endothelial cell proliferation, migration, invasion, and vascular tube formation, suggesting a mechanism of angiogenesis inhibition through direct action on VEGF receptors [22].

Figure 3: TA inhibits VEGF165-induced overexpression and activation of VEGF receptors on HUVEC cells. (A) Expression of VEGFR-1, VEGFR-2, and NRP-1 on HUVEC cells in response to 0 or 10 ng/mL VEGF165, with or without incubation with 1 mg/mL TA for 48 hours. (B) Tyrosine phosphorylation of VEGFR-1 and VEGFR-2 on HUVEC cells in response to 0 or 10 ng/mL VEGF165 for 5 minutes, with or without pre-treatment with 1 mg/mL TA for 48 hours. TA: Tranexamic Acid. P-VEGFR-1: Phosphorylated VEGFR-1. P-VEGFR-2: Phosphorylated VEGFR-2. β-actin was used as a loading control to normalize protein levels [22]

A similar phenomenon was observed in human melanocytes: VEGF165 increased VEGFR expression and promoted phosphorylation of these receptors on melanocytes, and TA diminished this process. As a result, TA was as effective as VEGFR-1/VEGFR-2 neutralization in inhibiting tyrosinase activity, reducing melanin production, and decreasing the expression of melanogenesis-related proteins induced by VEGF165.

The authors suggest that TA can inhibit angiogenesis and melanogenesis in vitro, at least in part, by targeting VEGF receptors, and this finding may contribute to further elucidating the pathogenesis of melasma as well as the molecular mechanism of TA in treating this condition [22].

3.2.3. TGF-β1 pathway

In this in vitro study, TA partially inhibited melanogenesis by stimulating TGF-β1 expression in human epidermal keratinocytes. TGF-β1 is one of the paracrine factors shown to contribute to the downregulation of melanin synthesis through signaling from keratinocytes/fibroblasts to melanocytes. The existence of this mechanism suggests that TA can affect the paracrine signaling network between skin cell types through more than one pathway, not limited to the plasmin-VEGF axis. The in vitro study showed that TA can stimulate TGF-β1 expression in keratinocytes, thereby reducing melanogenesis through paracrine signaling [20].

3.3. Safety and side effects

Topical TA is a safe treatment and has been shown to be better tolerated than topical hydroquinone (HQ) [11].

A randomized, double-blind study compared topical 5% TA with 2% HQ in 60 women over 12 weeks. Although there was no statistically significant difference between the two groups, the TA group reported higher patient satisfaction and fewer side effects compared to the HQ group [2]. Another similar study compared topical 5% TA solution with 3% HQ cream in 100 participants with skin of color. Participants applied one of the two products once daily, combined with SPF 30, for 12 weeks. The study also noted that the HQ group had a higher incidence of irritation and erythema, leading to a statistically significantly higher patient satisfaction level in the TA group [8].

Another trial used 2% TA in two forms: emulsion and sheet mask. Participants were instructed to use the emulsion twice daily and the mask three times weekly for 12 weeks. Fontana-Masson staining results on biopsy samples showed a significant reduction in epidermal pigmentation. Additionally, VEGF and endothelin-1 tended to decrease, suggesting that topical TA is effective in reducing the number of dermal blood vessels and melanogenesis [10].

Overall, topical TA is an effective and safe treatment for melasma, with fewer side effects compared to traditional topical HQ treatment. HQ is sometimes combined with topical corticosteroids to mitigate these side effects, but the addition of corticosteroids introduces a new set of potential side effects. The studies above highlight the good tolerability and high patient satisfaction with topical TA, making topical TA a useful complementary treatment option for melasma [11].

4. Discussion

The aggregated data above show that TA has a distinct mechanistic position compared to classic tyrosinase inhibitor active ingredients: instead of acting at the final stage of pigment production (tyrosinase enzyme), TA intervenes at a higher upstream level – by inhibiting plasmin, thereby simultaneously affecting both the pigment production pathway (via prostaglandins) and the angiogenesis pathway (via VEGF), along with an additional effect via TGF-β1 [5, 20, 22].

This multi-mechanism characteristic suggests that TA is suitable for controlling the initiation and maintenance stages of the disease process, especially the inflammatory and vascular components – while tyrosinase inhibitors and skin barrier support agents still play an essential role at other stages of pigment production. This multi-mechanism approach aligns with the recent general trend in aesthetics for treating melasma, which emphasizes that no single active ingredient can completely resolve a multi-factorial condition like melasma.

It should be noted that most of the evidence on the molecular mechanism of TA (especially its direct effect on VEGFR) currently comes from in vitro studies, while clinical evidence of treatment efficacy mainly comes from case series and small to medium-sized clinical trials. Therefore, the level of evidence for each specific mechanism should be interpreted cautiously, and recommendations for specific dosages and routes of administration should be based on a comprehensive clinical evaluation for each patient [22].

5. Illustrative Application: Tranexamic Acid in a Multi-layer Formula

Melasma is a multifactorial hyperpigmentation condition, where melanin production is simultaneously influenced by light, inflammation, intercellular signals, and changes in the dermal microenvironment – vascular system. A mechanistically sound treatment formula should combine multiple groups of active ingredients, each targeting a specific stage of pathogenesis, rather than relying solely on a single pigment-inhibiting active ingredient.

Based on this principle, oh!oh! Dark Spot Fading Serum (with 3% Tranexamic Acid, 10% Niacinamide, 2.5% Dark Fade Complex, 1% Bakuchiol & 1% MSR™ Blend) can be used as an illustrative example of how to build a multi-active formula, where the ingredients are chosen to act on multiple stages of the hyperpigmentation process.

Regarding efficacy data, an internal survey of 23 subjects (average age 57.6), using the product for 4 weeks, recorded a significant reduction in measured melanin concentration and no adverse skin reactions reported by participants or observed by dermatologists. It should be noted that this is a small-scale survey, sponsored by the manufacturer, without a randomized control group, and has not been published in a peer-reviewed scientific journal. Therefore, it should only be considered as a reference data point for skin tolerability, not a substitute for evidence from larger controlled clinical trials.

6. References

1. AlJabr, A., A.M.I. AlAnazi, and R.A.A. AlEtebi, Tranexamic Acid for Hyperpigmentation Disorders: A Literature Review on Efficacy and Safety in Melasma and PIH. J Cosmet Dermatol, 2026. 25(2): p. e70692.

2. Atefi, N., et al., Therapeutic Effects of Topical Tranexamic Acid in Comparison with Hydroquinone in Treatment of Women with Melasma.Dermatol Ther (Heidelb), 2017. 7(3): p. 417-424.

3. Chen, T., J. Xue, and Q. Wang, Tranexamic acid for the treatment of hyperpigmentation and telangiectatic disorders other than melasma: An update. Clinical, cosmetic and investigational dermatology, 2024: p. 2151-2163.

4. Desai, S.R., et al., Best practices in the treatment of melasma with a focus on patients with skin of color. Journal of the American Academy of Dermatology, 2024. 90(2): p. 269-279.

5. Foss, M., et al., Oral tranexamic acid for the treatment of melasma: a case series and novel dosing regimen. Journal of Drugs in Dermatology: JDD, 2022. 21(4): p. 393-398.

6. Gaćina, K. and A. Krstanović Ćosić, THE USE OF TRANEXAMIC ACID IN DERMATOLOGY. Acta Clin Croat, 2023. 62(2): p. 368-372.

7. Handel, A.C., L.D. Miot, and H.A. Miot, Melasma: a clinical and epidemiological review. An Bras Dermatol, 2014. 89(5): p. 771-82.

8. Janney, M.S., et al., A Randomized Controlled Study Comparing the Efficacy of Topical 5% Tranexamic Acid Solution versus 3% Hydroquinone Cream in Melasma. J Cutan Aesthet Surg, 2019. 12(1): p. 63-67.

9. Kaur, A., M. Bhalla, and R. Sarkar, Tranexamic acid in melasma: a review. Pigment International, 2020. 7(1): p. 12-25.

10. Kim, S.J., et al., Efficacy and possible mechanisms of topical tranexamic acid in melasma. Clin Exp Dermatol, 2016. 41(5): p. 480-5.

11. Konisky, H., et al., Tranexamic acid in melasma: A focused review on drug administration routes. Journal of cosmetic dermatology, 2023. 22(4): p. 1197-1206.

12. Kumar, D., R. Sood, and P. Tiwari, Melasma management: Unveiling recent breakthroughs through literature analysis. Health Sciences Review, 2025. 14: p. 100213.

13. Kwon, S.-H., et al., Heterogeneous pathology of melasma and its clinical implications. International journal of molecular sciences, 2016. 17(6): p. 824.

14. Lee, A.Y., Recent progress in melasma pathogenesis. Pigment cell & melanoma research, 2015. 28(6): p. 648-660.

15. Liu, W., Q. Chen, and Y. Xia, New Mechanistic Insights of Melasma. Clin Cosmet Investig Dermatol, 2023. 16: p. 429-442.

16. Majid, I. and S. Aleem, Melasma: update on epidemiology, clinical presentation, assessment, and scoring. 2021.

17. McKesey, J., A. Tovar-Garza, and A.G. Pandya, Melasma Treatment: An Evidence-Based Review: J. McKesey et al. American journal of clinical dermatology, 2020. 21(2): p. 173-225.

18. Naba, A., Mechanisms of assembly and remodelling of the extracellular matrix. Nature Reviews Molecular Cell Biology, 2024. 25(11): p. 865-885.

19. Wu, M.X., R. Antony, and H.N. Mayrovitz, Melasma: a condition of Asian skin. Cureus, 2021. 13(4).

20. Xing, X., et al., Tranexamic acid inhibits melanogenesis partially via stimulation of TGF‐β1 expression in human epidermal keratinocytes.Experimental dermatology, 2022. 31(4): p. 633-640.

21. Zhang, C., T. Wu, and N. Shen, Effect of platelet-rich plasma combined with tranexamic acid in the treatment of melasma and its effect on the serum levels of vascular endothelial growth factor, endothelin-1 and melatonin. Pak J Med Sci, 2022. 38(8): p. 2163-2168.

22. Zhu, J.W., et al., Tranexamic Acid Inhibits Angiogenesis and Melanogenesis in Vitro by Targeting VEGF Receptors. Int J Med Sci, 2020. 17(7): p. 903-911.