First-Line Treatment for Melasma in Women of Childbearing Age
Start with triple combination cream (hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%) combined with strict broad-spectrum sunscreen (SPF 50+) reapplied every 2-3 hours during sun exposure. 1, 2
Foundational Sun Protection (Non-Negotiable)
Sun protection is the absolute foundation—without it, no treatment will succeed. 1, 2, 3
- Apply broad-spectrum sunscreen SPF 50+ every morning and reapply every 2-3 hours during outdoor exposure 1, 2
- Reapply immediately after swimming or sweating—this is where most patients fail 1, 2
- Wear wide-brimmed hats (>3 inches) when outdoors 1, 2
- Seek shade during peak UV hours (10 AM to 4 PM) 1, 2
- Use UV-protective clothing with tight weave fabrics and darker colors 1, 2
- Completely avoid tanning beds and sunlamps 1, 2
First-Line Topical Therapy
Triple combination cream is the gold standard first-line treatment with the strongest evidence base. 1, 3, 4
The formulation contains:
- Hydroquinone 4% (melanin synthesis inhibitor) 1, 3, 4
- Tretinoin 0.05% (increases epidermal turnover and enhances penetration) 1, 3, 4
- Fluocinolone acetonide 0.01% (reduces irritation and enhances penetration) 1, 3, 4
Apply once nightly to affected areas for 8-12 weeks before assessing response. 4, 5
Alternative First-Line Options if Triple Combination Unavailable
- Hydroquinone 4% alone (Grade A recommendation) 3
- Azelaic acid 15-20% (Grade A recommendation, safer in pregnancy if needed) 3
- Kojic acid (Grade A recommendation) 3
When to Escalate to Second-Line Treatment
If inadequate response after 8-12 weeks of triple combination cream plus strict sun protection, add intradermal platelet-rich plasma (PRP) injections. 1, 2, 6
PRP Injection Protocol
- Administer 4 treatment sessions spaced every 2-3 weeks 1, 2, 6
- Inject intradermally at 1 cm intervals across affected areas 1, 6
- Follow-up evaluation one month after the last treatment 1, 2
- PRP demonstrates superior efficacy compared to intradermal tranexamic acid with similar side effect profiles 1, 2, 6
- Mean mMASI score reduction of 45.67% with PRP versus lower reductions with other modalities 2, 6
Consider Adding Oral Tranexamic Acid
For enhanced efficacy, add oral tranexamic acid 250 mg twice daily when initiating PRP therapy. 1, 2, 6
- PRP combined with oral tranexamic acid shows 90.48% total efficacy versus 73.68% with tranexamic acid alone 1, 2, 6
- Lower disease recurrence rates with combination therapy 1, 2, 6
- Screen for contraindications to tranexamic acid (history of thromboembolism, stroke, cardiovascular disease) 3
Long-Term Maintenance Strategy
Melasma is a chronic relapsing condition requiring indefinite maintenance therapy—this is critical to communicate upfront. 1, 2, 7, 5
- Continue strict sun protection indefinitely 1, 2, 5
- Maintenance PRP treatments every 6 months 1, 2, 6
- Consider intermittent topical therapy (2-3 times weekly) to prevent recurrence 5
Measuring Treatment Success
Use objective measurements, not just clinical impression:
- Modified Melasma Area and Severity Index (mMASI) scores to track improvement 1, 2, 6
- MASI reduction >60-90% indicates moderate improvement 1, 2
- MASI reduction >90% indicates excellent response 1, 2
- Combine with patient satisfaction assessment 1, 2
Critical Pitfalls to Avoid
Discontinuing treatment prematurely is the most common cause of treatment failure. 1, 6
- Forgetting sunscreen reapplication after 2-3 hours, swimming, or sweating is where most patients fail 1, 2
- Not addressing hormonal triggers (oral contraceptives, pregnancy, hormone replacement therapy) may limit success 1, 8
- Counsel patients to avoid smoking, which worsens melasma 1, 2
- Approximately 40% of patients develop erythema and peeling with triple combination cream—this is expected and manageable, not a reason to stop 4
Special Considerations for Women of Childbearing Age
Hormonal changes from pregnancy or oral contraceptives are major triggers—address these directly. 8, 7