What is the recommended treatment for a patient with melasma, considering potential hormonal and thyroid disease factors?

Melasma Treatment

Start with triple combination cream (hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%) combined with strict sun protection (SPF 50+ broad-spectrum sunscreen), and if inadequate response after 8-12 weeks, add intradermal platelet-rich plasma (PRP) injections every 2-3 weeks for 4 sessions. 1

First-Line Treatment Protocol

Begin all patients with the following combination approach:

Topical Therapy

• Triple combination cream remains the most effective topical treatment (hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%) 1, 2, 3
• Hydroquinone 4% is FDA-approved for gradual bleaching of melasma and works by inhibiting enzymatic oxidation of tyrosine to dopa, suppressing melanocyte metabolic processes 4
• Apply once daily in the evening 1
• Approximately 40% of patients develop erythema and peeling with triple combination therapy, but adverse events are typically mild and short-lasting 3

Mandatory Sun Protection (Foundation of All Treatment)

• Apply broad-spectrum sunscreen SPF 50+ and reapply every 2-3 hours during outdoor exposure 1
• Wear wide-brimmed hats (>3-inch brim) when outdoors 1
• Seek shade during peak UV hours (10 a.m. to 4 p.m.) 1
• Use UV-protective clothing with tight weave fabrics and darker colors 1
• Avoid tanning beds and sunlamps completely 1
• UV exposure will cause repigmentation of bleached areas, making sun protection non-negotiable 4

Second-Line Treatment for Inadequate Response After 8-12 Weeks

Intradermal PRP Injections

PRP demonstrates superior efficacy compared to all other advanced treatments, including tranexamic acid injections 5, 6, 1

Treatment Protocol:

• Administer 4 intradermal PRP treatment sessions spaced every 2-3 weeks 1
• Inject intradermally at 1 cm intervals across affected areas 6, 1
• Significant improvement occurs within 6 weeks as measured by modified Melasma Area and Severity Index (mMASI) scores 5, 6, 1
• Follow-up evaluation one month after the last treatment 1
• Mean mMASI score reduction with PRP is 45.67-53.66% 6
• Patient satisfaction rates exceed 90% with PRP treatment 6

Adjunctive Oral Tranexamic Acid

Consider adding oral tranexamic acid 250 mg twice daily, particularly when combined with PRP injections 6, 1

• PRP combined with oral tranexamic acid demonstrates higher total efficacy (90.48%) compared to tranexamic acid alone (73.68%) 5, 1
• Lower disease recurrence rates with combination therapy 5, 1
• Oral tranexamic acid is more effective than topical tranexamic acid for hyperpigmentation 5
• This is a promising treatment for moderate and severe recurrent melasma 2, 7

Measuring Treatment Success

Use objective measurements to track progress:

• Standardized mMASI scores should be used to objectively track improvement 6, 1
• Decreases in MASI >60-90% indicate moderate improvement 6, 1
• Decreases in MASI >90% indicate excellent response 6, 1
• Patient satisfaction assessment should complement objective measurements 6, 1

Long-Term Maintenance (Essential for This Chronic Condition)

Melasma is a chronic condition with high recurrence rates requiring long-term maintenance therapy 6, 1

• Continue strict sun protection indefinitely 1
• Continue topical therapy as tolerated 1
• Maintenance PRP treatments every 6 months 5, 6, 1
• Consider intermittent use of topical agents 5

Alternative Consideration

Microneedling may be more effective than intradermal PRP injections for melasma treatment in some patients 6, 1

• Consider microneedling as alternative to PRP if PRP is unavailable or ineffective 1
• Three treatment sessions spaced at least 21 days apart with maintenance every 6 months 6

Critical Pitfalls to Avoid

• Discontinuing treatment too early—melasma requires long-term maintenance therapy 5, 1
• Forgetting to reapply sunscreen after swimming, sweating, or after 2-3 hours of continuous exposure 1
• Failing to address hormonal influences (pregnancy, oral contraceptives, hormone replacement therapy) that may limit treatment success 6, 1
• Counsel patients to avoid smoking, which can worsen melasma 6, 1
• Using chemical peels or laser therapies in darker-skinned individuals carries increased risk of post-inflammatory hyperpigmentation 3

Addressing Hormonal and Thyroid Factors

• Genetic factors and hormonal influences may limit treatment success in some patients 6
• Pregnancy, oral contraceptives, and hormone replacement therapy are established etiologic factors 7, 8
• Address modifiable hormonal factors when possible, though treatment can still proceed with the above algorithm 1
• Thyroid disease should be evaluated and managed appropriately, though specific evidence linking thyroid treatment to melasma improvement is limited in the provided literature