What is a depigmenting agent?

Dark spots, melasma, age spots (lentigines), or post-inflammatory hyperpigmentation are some of the most common skin pigmentation disorders. To treat them, depigmenting substances or procedures are used to help even out the skin tone and reduce the excessive production or accumulation of melanin.

How does a depigmenting agent work?

A depigmenting agent is a substance (whether topical, oral, or physical) designed to reduce skin pigmentation. It works by inhibiting melanin synthesis (the pigment responsible for skin color), accelerating cell turnover, or promoting the elimination of accumulated pigments.

Hyperpigmentation is characterized by a focal or diffuse increase in melanin in the epidermis and/or dermis. In melasma, for example, the excessive activation of melanocytes is triggered by hormonal stimuli, UV exposure, and inflammatory factors, along with vascular alterations and disruptions in the skin barrier.

Mechanism of action of a depigmenting agent

Depigmenting agents can act through one or more of the following mechanisms:

1. Inhibition of tyrosinase: it is the key enzyme in melanin production. Agents such as hydroquinone, arbutin, or kojic acid block its activity.
2. Antioxidation: substances like vitamin C (ascorbic acid) prevent the oxidation of dopaquinone, an intermediate in the melanin pathway, reducing the formation of melanin.
3. Exfoliation: fruit acids (glycolic, lactic, mandelic acids) and retinoids promote epidermal turnover, facilitating the removal of melanosomes in keratinocytes.
4. Inhibition of melanin transfer: some peptides and natural extracts interfere with the transfer of melanin granules from melanocytes to keratinocytes.

Depigmenting agents are mainly used in:

• Melasma: associated with hormones or sun exposure.
• Solar or age spots: flat spots on the backs of the hands or face.
• Post-inflammatory hyperpigmentation: after acne, burns, or aggressive procedures.
• Ota’s nevus and other focal pigmentations: with specific protocols and, sometimes, combined with laser treatment.

Depigmenting agents in aesthetic medicine require a multimodal and personalized approach. The combination of enzymatic inhibitors, exfoliants, and angiogenesis modulators, along with strict sun protection, optimizes results and minimizes complications.

To enhance results and reduce adverse effects, it is common to combine the use of depigmenting agents with chemical peels, transdermal electroporation, lasers, and radiofrequency.

Recent evidence supports the efficacy of TXA as an adjunct and mesotherapy protocols, consolidating new alternatives to the HQ standard. Continuous follow-up and patient education are essential for long-term success.

Classification of depigmenting agents

Depigmenting agents can be classified as follows:

• Enzymatic inhibitors of melanogenesis
  • Hydroquinone (HQ): gold standard, irreversibly inhibits tyrosinase.
  • Kojic acid, arbutin: reversible inhibition of tyrosinase with an antioxidant profile.
• Exfoliating/Chemical agents
  • Glycolic, mandelic, salicylic acids: accelerate epidermal turnover and the removal of melanosomes.
• Antioxidant and immunomodulatory agents
  • Vitamin C (ascorbic acid), niacinamide: neutralize free radicals and prevent the oxidation of melanin intermediates.
• Emerging agents and modulators of melanosome transfer
  • Tranexamic acid (TXA): anti-angiogenic, anti-inflammatory, and anti-melanogenic, inhibiting plasminogen activation and reducing vascular proliferation in melasma.
  • Depigmenting peptides: block the transfer of melanosomes (e.g., Pentapeptide-3).

Hydration

Photoaging

Skin