Retinoids in Skincare: Tretinoin and Tazarotene

Written by Abida Mozid, BSc Biomedical Science

Retinoids are a powerful class of topical treatments championed across the field of dermatology. They are derivatives of Vitamin A, often used for photoaging and anti-aging. ⁽¹⁾ Tretinoin is more commonly known and is established as the gold standard of prescription strength retinoids. There is a lesser-known retinoid called tazarotene, which operates similarly but has different indications.

Both retinoids can effectively transform skin at the molecular level. So how do they work and what are they used for?

The Mechanism of Retinoid Activity

1. Both tretinoin and tazarotene function by attaching themselves to the nuclear retinoic acid receptors (RARs) present in skin cells:

   • RAR-α

   • RAR-β

   • RAR-γ

     
     

2. These receptors operate as transcription factors, which directly turn genes on or off. ^(2,3,4)

   
   

3. The retinoid-receptor complex then binds to specific DNA regions, called retinoic acid response elements (RAREs), which alters the transcription of certain genes. ^(2,3,4)

   
   

4. This triggers the production of messenger RNA (mRNA) from the genes, which instruct the cell to produce different proteins. ^(2,3,4) 

   
   

These are the proteins involved in:

• Skin cell growth

• Collagen production

• Keratinisation

• Wound repair

• Controlling inflammation

How Retinoids Impact the Skin

Increased Epidermal Cell Turnover

Older skin cells shed more consistently, allowing new cells to develop at the surface more effectively. Retinoids also help to regulate keratinisation through RAR activation, reducing excess keratin and cell adhesion inside pores. ^{(2, 3, 4, 5)}

These mechanisms lead to less acne and clogged pores, decreased rough or scaly texture and prevention of comedone formation. In conditions like psoriasis, they can reduce the formation of excess or abnormal plaque/scaling. ^{(1, 2, 3, 4, 5)}

Collagen Synthesis and Wound Repair

Retinoids can gradually improve the appearance of fine lines/wrinkles and boost skin firmness, by stimulating fibroblasts to produce more collagen and extracellular matrix components, necessary for tissue repair.

Retinoids also inhibit transcription factors such as AP-1, which raise collagen-degrading enzymes such as matrix metalloproteinases (MMPs), particularly following UV exposure. Suppressing this pathway can contribute to reduced collagen breakdown over time. ^{(2, 3, 4, 5)}

Inflammatory Regulation

Although retinoids can initially cause skin irritation or sensitivity due to increased skin cell turnover, they gradually lower inflammatory signalling overall. This helps to reduce redness and acne in the skin. ^{(2, 3, 4, 5)}

Tolerability and Application of Tretinoin and Tazarotene

Tretinoin has approximate affinity for all 3 RAR-subtypes (α, β, and γ), binding to them non-selectively. It also degrades more readily with exposure to light, heat and oxygen, compared to tazarotene. Due to this activity, it is frequently regarded as the more tolerated prescribed retinoid for long-term anti-aging. ^{(2, 3, 4, 5)}

Tazarotene exhibits greater selectivity for RAR-β AND RAR-γ specifically, and has a higher resistance to metabolic breakdown compared to tretinoin. This makes it a more potent and biologically direct topical treatment, contributing to a potential increased risk of irritation.

However, these same properties of tazarotene are what makes it more effective to treat plaque psoriasis and in certain cases, resistant acne. There is also evidence suggesting it can produce faster results in skin transformation for photoaging. ^{(1, 2, 3, 4, 5)}

Visible improvements from consistent retinoid use can take 6-12 months to manifest for many users, due to:

• Collagen synthesis being a slow and gradual process

• Skin cells continuing to regenerate in cycles

• Adjusting to the initial disruption of the skin barrier ⁽⁴⁾

Possible Side Effects of Retinoid Use

Common side effects of retinoids include:

• Stinging/burning sensation

• Dry skin

• Peeling skin

• Redness

• Irritated and sensitive skin

These usually occur during the initial months of application. It is recommended to incorporate retinoids slowly at first to allow the skin to adjust, before building up frequency. This will help to reduce the risk of side effects.⁽⁵⁾ Individuals who struggle more with tolerating retinoids can also:

• Apply retinoids on top of moisturisers and barrier creams

• Avoid application on more sensitive areas of the face (such as the mouth or eye area)

Summary

Tretinoin and tazarotene can help with acne, skin texture, hyperpigmentation, and certain indications of photoaging over time. In general, tretinoin is the more commonly used retinoid and is frequently better tolerated. Tazarotene acts more potently which is useful for more targeted treatment of certain conditions, but this can come with an increased risk of irritation. However, tretinoin can still trigger similar side effects, so managing either retinoid with caution is crucial in a skincare routine.

Regarding both retinoids, being consistent and patient is necessary to see any true visible results. Tailoring retinoid use to each individual’s level of skin tolerability and condition, will provide the best results and successful, long-lasting benefits.

References

1. Menezes, M.S.S. and Almeida, C.M.M. (2024). Structural, functional, nutritional and clinical aspects of vitamin A: a review. PharmaNutrition, [online] 27, p.100383. doi:https://doi.org/10.1016/j.phanu.2024.100383.

   
   

2. Milosheska, D. and Roškar, R. (2022). Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations. Advances in Therapy, [online] 39(12), pp.5351–5375. doi:https://doi.org/10.1007/s12325-022-02319-7.

   
   

3. Sitohang, I.B.S., Makes, W.I., Sandora, N. and Suryanegara, J. (2022). Topical tretinoin for treating photoaging: A systematic review of randomized controlled trials. International Journal of Women’s Dermatology, 8(1), p.e003. doi:https://doi.org/10.1097/jw9.0000000000000003.

   
   

4. Balado-Simó, P., Morgado-Carrasco, D., Gómez-Armayones, S., López-Ferrer, A., Barco, D., Ferrándiz-Pulido, C. and Podlipnik, S. (2025). An Updated Review of Topical Tretinoin in Dermatology: From Acne and Photoaging to Skin Cancer. Journal of Clinical Medicine, [online] 14(22), p.7958. doi:https://doi.org/10.3390/jcm14227958.

   
   

5. Khanna, C., Sharma, P., Kaur, S., Singh, S., Rahar, S., Kumar, L., Soni, V., Kaur, C., Kaur, P. and Kaur, C. (2022). TAZAROTENE: A Concise Review of Mechanism of Action and Therapeutic Benefits. International Journal of Life Science and Pharma Research, pp.P207–P219. doi:https://doi.org/10.22376/ijpbs/lpr.2022.12.6.p207-219.

Assessed and Endorsed by the MedReport Medical Review Board