What is the effectiveness of Tretinoin (all-trans retinoic acid) for treating age spots (lentigines)?

From the Guidelines

Tretinoin is effective for treating age spots, and the most effective concentration is 0.3% as it has been shown to achieve complete clearance of actinic keratoses in 55% of subjects treated, as reported by Bollag and Ott 1. When using tretinoin for age spots, it is essential to start with a lower concentration, such as 0.025%, and gradually increase as the skin builds tolerance to minimize irritation.

• Apply a pea-sized amount of tretinoin cream or gel to the affected areas once daily, preferably at night after cleansing and completely drying your skin.
• Results typically take 2-3 months of consistent use, and tretinoin works by increasing cell turnover, helping to fade hyperpigmentation by bringing newer, unpigmented cells to the surface while promoting the shedding of the darkened cells.
• While using tretinoin, apply sunscreen (SPF 30+) daily as the medication increases sun sensitivity.
• Common side effects include redness, dryness, peeling, and irritation, which usually subside as your skin adjusts.
• If irritation is severe, reduce frequency of application or consult a healthcare provider.
• Moisturize regularly to minimize dryness, and avoid using harsh skincare products simultaneously with tretinoin. According to the British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017, topical retinoids, including tretinoin, may lend some additional benefit with respect to improvement in lentigines and reduced wrinkles 1. However, the most recent and highest quality study, which is the 2017 guidelines, recommends using adapalene 0.3% as it was significantly more efficacious in achieving AK count reduction after 9 months compared to 0.1% concentration 1. But since the question is about tretinoin, the recommended concentration of tretinoin is 0.3% as it has been shown to be more effective than lower concentrations, such as 0.1%.

From the Research

Tretinoin for Age Spots

• Tretinoin, also known as Retin-A, is a topical treatment that has been shown to be effective in reducing the appearance of age spots and other signs of photoaged skin 2.
• It works by enhancing the appearance of photoaged skin, effacing fine wrinkles, bleaching pigmented "age spots," improving surface texture, and inducing a rosy glow 2.
• Tretinoin is considered the most effective agent with proven antiaging effects on the skin and can be found in formulations approved as medicines for topical treatment of acne, facial wrinkles, and hyperpigmentation 3.

Mechanism of Action

• The development of age spots is strongly related to chronic sun exposure and is associated with photodamage and an increased risk for skin cancer 4.
• The increased expression of keratins 5 and 10, markers of basal and suprabasal keratinocytes, respectively, in age spots suggests that the increased proliferation of basal keratinocytes combined with the decreased turnover of suprabasal keratinocytes leads to the exaggerated formation of rete ridges in lesional epidermis which in turn disrupts the normal processing of melanin upwards from the basal layer 4.

Comparison with Other Treatments

• Tretinoin is currently the gold standard therapy for the treatment of photoaging, but its poor tolerability often limits its use 5.
• Other topical medications and cosmeceuticals have been compared to tretinoin, but most studies found the comparator to be less irritating and better tolerated by patients than tretinoin 5.
• Retinoid precursors, such as retinaldehyde, pro-retinal nanoparticles, and conjugated alpha-hydroxy acid and retinoid (AHA-ret), can be considered a second-line option for anti-aging treatment in patients who cannot tolerate tretinoin 5.

Age Spots as a Medical Issue

• Senile lentigo or age spots are hyperpigmented macules of skin that occur in irregular shapes, appearing most commonly in the sun-exposed areas of the skin such as on the face and back of the hands 6.
• There are discussions on whether senile lentigo represents a melanoma precursor, and if there is a need for a regular follow-up in cases of multiple lesions 6.
• Cryotherapy and laser treatment are common therapeutic approaches for age spots, and sun protection creams may be useful in early lesions 6.