Melasma is a chronic, relapsing hyperpigmentation disorder that primarily affects sun-exposed areas of the skin, especially the face. It is characterized by irregular, brownish macules and patches with a symmetric distribution, commonly involving the cheeks, forehead, upper lip, and chin. Although melasma can occur in both sexes, it predominantly affects women, particularly those of reproductive age, due to its strong association with hormonal changes [1, 2].

One of the most common physiological triggers for melasma is pregnancy, wherein it is referred to as chloasma or the "mask of pregnancy." The prevalence of melasma among pregnant women has been reported to range between 15% to 50%, depending on geographic, ethnic, and environmental factors. Hormonal fluctuations during pregnancy—specifically elevated levels of estrogen, progesterone, and melanocyte-stimulating hormone (MSH)—play a pivotal role in stimulating melanogenesis, leading to increased pigmentation [4, 5]. Additionally, factors such as ultraviolet (UV) radiation, genetic predisposition, and the use of certain cosmetics or medications may exacerbate the condition [1, 3].

In many cases, melasma persists beyond pregnancy into the postpartum period, often causing cosmetic concern and emotional distress [1, 5, 6]. The psychosocial impact of melasma can be substantial, affecting self-esteem and quality of life, thereby necessitating timely and effective intervention [1].

Therapeutic management of melasma is challenging due to its multifactorial etiology, chronic course, and high recurrence rate. Topical agents such as hydroquinone, azelaic acid, kojic acid, and sunscreens form the mainstay of treatment and are commonly prescribed during pregnancy due to their favorable safety profile [7]. However, their efficacy is often limited and gradual. On the other hand, systemic therapies, particularly oral tranexamic acid, have shown promising results in the postpartum period, providing more rapid and significant pigment reduction [7, 8]. Nevertheless, systemic agents are contraindicated during pregnancy, restricting their use to postpartum women.

Despite the availability of multiple therapeutic options, there remains a paucity of comparative clinical data on the effectiveness of topical versus systemic treatments in pregnant and postpartum populations. Understanding the differential therapeutic outcomes in these two groups is essential for optimizing treatment strategies while ensuring safety and efficacy.

This study, therefore, aims to evaluate and compare the efficacy and safety of topical therapies in pregnant women with melasma and both topical and systemic therapies in postpartum women. By analyzing the clinical outcomes and adverse effects across these groups, we seek to provide evidence-based recommendations for individualized, phase-specific management of melasma in women during and after pregnancy.

Place and Duration of the Study:

This prospective, comparative clinical study was conducted over a period of 12 months, from March 2019 to February 2020, in the Department of Dermatology, in collaboration with the Department of Obstetrics and Gynaecology, at a tertiary care teaching hospital.

A total of 60 female patients clinically diagnosed with facial melasma were enrolled in the study and categorized into two groups based on their reproductive status: pregnant women (n = 30) and postpartum women (n = 30). All participants provided written informed consent prior to enrolment.

Inclusion Criteria:

Women aged between 20 and 40 years, clinically diagnosed with melasma, who were either in the second or third trimester of pregnancy or within six months postpartum, were included in the study. Only those with epidermal or mixed-type melasma confirmed by Wood's lamp examination were selected. Participants were required to be willing to follow up regularly for the duration of the study.

Exclusion Criteria:

Women with pre-existing dermatological conditions affecting facial skin (e.g., acne, psoriasis), a history of hypersensitivity to the study medications, liver dysfunction, coagulopathies, or concurrent use of hormonal therapies or photosensitizing agents were excluded. Additionally, patients with dermal-type melasma, active systemic infections, or those undergoing any cosmetic treatments for pigmentation were also excluded from the study.

Study Protocol:

Participants were divided into two main cohorts based on their reproductive status. Group A consisted of 30 pregnant women who received only topical therapy, which included hydroquinone 2% cream, azelaic acid 20%, and a broad-spectrum sunscreen with SPF ≥ 30, all applied twice daily under dermatological supervision. Group B included 30 postpartum women, who were further randomized into two subgroups. Group B1 (n = 15) received the same topical regimen as Group A, while Group B2 (n = 15) was administered systemic therapy comprising oral tranexamic acid 250 mg twice daily for 12 weeks, in addition to sunscreen and regular dermatological follow-up.

The Melasma Area and Severity Index (MASI) score was used as the primary outcome measure. MASI scoring was performed at baseline, 8 weeks, and 16 weeks by the same dermatologist to ensure consistency and minimize inter-observer variability.

Ethical Considerations:

The study protocol was reviewed and approved by the Institutional Ethics Committee prior to commencement. All participants were thoroughly counseled regarding the nature and purpose of the study. Written informed consent was obtained from each patient in their preferred language. Confidentiality of patient identity and clinical information was maintained throughout the study. No systemic medications were administered to pregnant women in compliance with safety guidelines, and all treatments followed standard dermatological recommendations.

Statistical Analysis:

Statistical analysis was carried out using IBM SPSS software (version 25). Quantitative variables such as MASI scores were expressed as mean ± standard deviation (SD). Intra-group comparisons (baseline vs. post-treatment) were analyzed using the paired t-test, while inter-group comparisons were assessed using the independent samples t-test or ANOVA as appropriate. A p-value of less than 0.05 was considered statistically significant. Data were also graphically represented using bar charts and line graphs for trend analysis.

Study Population

A total of 60 female patients clinically diagnosed with melasma were enrolled. Participants were categorized into two primary groups based on reproductive status: Group A (pregnant women, n = 30) and Group B (postpartum women, n = 30). Group B was further divided into two subgroups: Group B1 (topical therapy, n = 15) and Group B2 (systemic therapy, n = 15). Baseline demographic characteristics, including age and skin phototype, were similar across all groups, with no statistically significant differences observed (p > 0.05).

Changes in MASI Scores Over Time

The MASI was used to evaluate treatment efficacy at baseline, 8 weeks, and 16 weeks. As shown in Table 1, baseline MASI scores were 12.8 ± 2.3 in Group A, 13.0 ± 2.0 in Group B1, and 13.2 ± 2.1 in Group B2.

Table 1: MASI Score Progression Over 16 Weeks

At 8 weeks, MASI scores declined to 10.2 ± 2.1, 10.6 ± 1.9, and 8.4 ± 1.7, respectively, across the three groups. By 16 weeks, the MASI scores were further reduced to 8.4 ± 1.9 in Group A (a 34.4% reduction, p < 0.01), 9.0 ± 1.8 in Group B1 (a 30.8% reduction, p < 0.05), and 6.5 ± 1.6 in Group B2 (a 50.8% reduction, p < 0.001). The postpartum systemic therapy group (Group B2) showed a statistically significant greater improvement when compared with the other two groups.

Adverse Effects

Topical therapy was well tolerated in both Group A and Group B1, with 4 participants (13.3%) reporting mild adverse effects such as erythema and skin irritation. These reactions were transient and resolved without intervention. No participants discontinued treatment due to side effects. Importantly, no adverse events were reported in the systemic therapy group (Group B2), indicating that oral tranexamic acid was safe and well tolerated in postpartum women.

Patient Satisfaction

Patient satisfaction was assessed at the end of 16 weeks using a 5-point Likert scale (1 = not satisfied, 5 = highly satisfied). The mean satisfaction scores were 3.4 ± 0.6 in Group A, 3.2 ± 0.5 in Group B1, and 4.3 ± 0.4 in Group B2. The systemic therapy group (Group B2) demonstrated significantly higher satisfaction levels compared to the two topical therapy groups (p < 0.05), reflecting improved treatment outcomes and patient-perceived benefits.

Melasma remains one of the most cosmetically distressing pigmentary disorders, particularly in women during hormonally active phases such as pregnancy and the postpartum period. Its management poses a clinical challenge owing to its chronicity, multifactorial etiology, and the necessity for safety-conscious interventions in reproductive-age patients [9, 10]. The present study undertook a comparative evaluation of the efficacy and tolerability of topical versus systemic therapies in pregnant and postpartum women, thereby addressing a significant gap in the personalized therapeutic approach to melasma.

The results of this study demonstrate a markedly superior clinical outcome in postpartum women receiving oral tranexamic acid, with a mean MASI score reduction of 50.8% at 16 weeks. This is in contrast to the 34.4% reduction observed in pregnant women and 30.8% in postpartum women treated with topical agents alone. These findings align with emerging evidence that supports the antifibrinolytic and anti-inflammatory properties of tranexamic acid in downregulating melanogenesis via inhibition of plasminogen activation and ultraviolet-induced angiogenic factors [11].

In contrast, the pregnant cohort was managed conservatively using a topical regimen comprising hydroquinone, azelaic acid, and sunscreen, which showed moderate efficacy. The limitations in therapeutic options during pregnancy—primarily due to concerns regarding teratogenicity—warrant such conservative measures [12-14]. Despite these constraints, the topical approach yielded statistically significant improvement without systemic complications, affirming its role as a safe, first-line strategy in pregnancy-associated melasma.

The minimal adverse effects encountered—limited to transient local irritation in a few subjects receiving topical therapy—underscore the overall safety profile of the employed agents. Notably, no adverse effects were reported with oral tranexamic acid in the postpartum group, corroborating findings from earlier randomized controlled trials that have affirmed its favorable tolerability when used within recommended doses and durations.

Moreover, the significantly higher patient satisfaction scores in the systemic therapy group reflect not only the quantitative improvement but also the subjective psychological relief associated with visible pigment reduction. Given the psychosocial impact of melasma, especially among young mothers, these outcomes are clinically meaningful.

While the findings are encouraging, some limitations merit consideration. The relatively small sample size and single-center design may constrain generalizability. Additionally, long-term follow-up was not included, and therefore, recurrence rates and sustained efficacy could not be assessed. Future studies with larger, multi-centric cohorts and longer follow-up durations are warranted to substantiate these observations and establish definitive treatment guidelines tailored to the reproductive phase.

This study underscores the differential therapeutic response of melasma treatment based on reproductive status. Topical therapy remains a safe and effective option during pregnancy, whereas systemic therapy with oral tranexamic acid provides significantly superior results in postpartum women, both in terms of clinical improvement and patient satisfaction. A phase-specific, individualized treatment approach, guided by safety profiles and patient preference, is pivotal in optimizing outcomes in melasma management.

Acknowledgments

The authors gratefully acknowledge the contributions of the Department of Obstetrics and Gynaecology for their collaboration, and the patients who participated in this study for their time and cooperation. We also thank the dermatology nursing staff for their assistance in patient follow-up and MASI scoring.

Conflict of Interest

The authors declare no conflict of interest related to this study. The research was conducted independently without any influence from pharmaceutical or commercial entities.

Funding Sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-

1. Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014 Sep-Oct;89(5):771-82. doi: 10.1590/abd1806-4841.20143063.
2. Sarvjot V, Sharma S, Mishra S, Singh A. Melasma: a clinicopathological study of 43 cases. Indian J Pathol Microbiol. 2009 Jul-Sep;52(3):357-9. doi: 10.4103/0377-4929.54993.
3. Grimes PE. Melasma. Etiologic and therapeutic considerations. Arch Dermatol. 1995 Dec;131(12):1453-7. doi: 10.1001/archderm.131.12.1453.
4. Filoni A, Mariano M, Cameli N. Melasma: How hormones can modulate skin pigmentation. J Cosmet Dermatol. 2019 Apr;18(2):458-463. doi: 10.1111/jocd.12877.
5. Jang YH, Lee JY, Kang HY, Lee ES, Kim YC. Oestrogen and progesterone receptor expression in melasma: an immunohistochemical analysis. J Eur Acad Dermatol Venereol. 2010 Nov;24(11):1312-6. doi: 10.1111/j.1468-3083.2010.03638.x.
6. Schwartz BK, Zashin SJ, Spencer SK, Mills LE, Sober AJ. Pregnancy and hormonal influences on malignant melanoma. J Dermatol Surg Oncol. 1987 Mar;13(3):276-81. doi: 10.1111/j.1524-4725.1987.tb03950.x.
7. Sarkar R, Gokhale N, Godse K, Ailawadi P, Arya L, Sarma N, et al. Medical Management of Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group. Indian J Dermatol. 2017 Nov-Dec;62(6):558-577. doi: 10.4103/ijd.IJD_489_17.
8. Shankar K, Godse K, Aurangabadkar S, Lahiri K, Mysore V, Ganjoo A, Vedamurty M, Kohli M, Sharad J, Kadhe G, Ahirrao P, Narayanan V, Motlekar SA. Evidence-based treatment for melasma: expert opinion and a review. Dermatol Ther (Heidelb). 2014 Dec;4(2):165-86. doi: 10.1007/s13555-014-0064-z.
9. Achar A, Rathi SK. Melasma: A clinico-epidemiological study of 312 cases. Indian J Dermatol. 2011;56(4):380–2.
10. Kang WH, Yoon KH, Lee ES, Kim J, Lee KB, Yim H. Melasma: Histopathological characteristics in 56 Korean patients. Br J Dermatol. 2002;146(2):228–37.
11. Lee HC, Thng TG, Goh CL. Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis. J Am Acad Dermatol. 2016;75(2):385–92.
12. Del Rosario E, Florez-Pollack S, Zapata L Jr, Hernandez K, Tovar-Garza A, Rodrigues M, et al. Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma. J Am Acad Dermatol. 2018;78(2):363–369.e1.
13. Gupta AK, Gover MD, Nouri K, Taylor S. The treatment of melasma: A review of clinical trials. J Am Acad Dermatol. 2006;55(6):1048–65.
14. Ogbechie-Godec OA, Elbuluk N. Melasma: An up-to-date comprehensive review. Dermatol Ther (Heidelb). 2017;7(3):305–18.