Isotretinoin, often know by its original brand name Accutane®, acts as an effective treatment for severe cystic acne by decreasing skin oil production, reducing bacteria, lowering inflammation, and increasing skin cell shedding. However, isotretinoin causes numerous permanent and irreversible side effects in the skin, which may impact skin aging.
Scientists have not yet concluded if oral isotretinoin leads to long-term skin aging, but they have discovered that it may cause prolonged reduction in the natural production of skin oil and lingering skin dryness. Whether this will cause the skin to age more quickly will require more research.
On the other hand, two studies have shown an improvement in sun-damaged skin in people taking isotretinoin in the short term. Sun damage is a sign of aging, so in this way, isotretinoin may help reduce this sign of aging in the short term.
Because of these conflicting reports, and a lack of long follow-up studies, researchers will need to perform more long follow-up studies for us to identify if oral isotretinoin affects the aging of skin.
Isotretinoin, often referred to by its original brand name, Accutane®, is a vitamin A derivative that is approved to treat severe cystic acne. It works by causing numerous changes in the skin, including reducing the amount of skin oil, reducing the amount of acne bacteria present in the skin, decreasing the amount of inflammation, and increasing the shedding of dead skin cells. These changes usually cause a dramatic improvement in acne in people taking isotretinoin.
However, isotretinoin can permanently reduce skin oil levels, and can result in dryer skin in the long term. It is unclear whether these effects can cause the skin to age more quickly, but is a concern of many people who are considering the drug or who have taken it in the past.1–4
Characteristics of Aged Skin
Throughout a person’s life, the speed of skin aging is dependent on genetics, which controls the body’s ability to produce important skin proteins, such as collagen and elastin, as well as lifestyle, which includes things like exposure to the sun or to harsh chemicals.5–8
Aged skin characteristics include:
- Increased skin dryness or roughness
- Increased fine and/or coarse wrinkling
- Changes in pigmentation (skin color)
- Decreased sebum (skin oil) production
- Decreased collagen production
- Decreased elasticity of the skin protein, elastin
Isotretinoin Effects on the Skin
Isotretinoin is a serious, systemic oral medication that permanently and irreversibly changes the body. It can also come with severe side effects. For these reasons, the FDA has approved isotretinoin only in cases of severe cystic acne.
Isotretinoin causes numerous changes in the skin, some of which are intended, and some of which are side effects.
Intended skin changes
- Decreased sebum production, which reduces acne bacteria
- Reduced skin inflammation
- Increased skin cell shedding and replacement
Side effects of isotretinoin
- Increased skin dryness (short term & long term)
- Increased skin thickness (short term)
- Inflammation of the lips and eye (short term)
- Dry eyes (usually short term)
- Changes in blood lipid levels (short term)
- Impaired liver function (short term)
- Fetal abnormalities in pregnant women (catastrophic, including death)
Almost all people taking isotretinoin will experience one or more of these side effects while on the medication.1,3,9-14
What Are the Long-Term Effects of Accutane?
Scientists have performed two studies in an attempt to identify how long the effects of isotretinoin last after stopping treatment. The first study followed people for one year and found that isotretinoin continues to reduce the level of sebum the skin produces for one year following treatment, and continues to produce skin dryness. No studies examined if this effect lasts longer than a year, but many people who have taken isotretinoin can attest to permanent changes in their skin, for instance the need to use lip balm for decades after treatment.
The second study followed patients for 4–9 years following isotretinoin treatment. The researchers found that 4–8% of patients reported long-term side effects, but the researchers did not look at signs of skin aging. Unfortunately, because this is the only study with a somewhat lengthy follow-up, we do not know how isotretinoin affects skin aging in the long term.1,3,9,11,12
Many anecdotal accounts of faster skin aging after isotretinoin abound on the Internet. This makes common sense based on the power of isotretinoin to permanently and irreversibly reduce the natural skin oil levels of the skin, but the bottom line is we simply do not have data to determine the long-term effects of isotretinoin on skin aging.
Two Studies Show Isotretinoin May Treat Short-Term Skin Aging
Isotretinoin has been tested in the short term on photoaged skin. “Photoaged skin” is skin that has been aged due to chronic sun exposure. To test the impact of isotretinoin on photoaged skin, scientists compared the pigmentation of patients taking isotretinoin to those not taking it. They found that oral isotretinoin resulted in a short-term improvement in the appearance of photoaged skin, and concluded that isotretinoin may treat photoaging.13 A second study found that isotretinoin may increase the thickness of the skin layer in the short term, which may decrease the appearance of aging.10
Because long follow-up clinical trials are severely limited, the existing studies do not provide a comprehensive view into how isotretinoin may affect long-term skin aging. Therefore, scientists need to perform more research before making any conclusions regarding oral isotretinoin and skin aging.
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- Leyden, J. J., Del Rosso, J. Q. & Baum, E. W. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J. Clin. Aesthet. Dermatol. 7, S3–S21 (2014).
- Mukherjee, S. et al. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin. Interv. Aging. 1, 327–348 (2006).
- Layton, A. The use of isotretinoin in acne. Dermatoendocrinol. 1, 162–169 (2009).
- Nelson, A. M. et al. Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 1, 177–187 (2009).
- Gragnani, A. et al. Review of Major Theories of Skin Aging. Adv. Aging Res. 3, 265–284 (2014).
- Ganceviciene, R., Liakou, A. I., Theodoridis, A., Makrantonaki, E. & Zouboulis, C. C. Skin anti-aging strategies. Dermatoendocrinol. 4, 308–319 (2012).
- Naval, J., Alonso, V. & Herranz, M. A. Genetic polymorphisms and skin aging: The identification of population genotypic groups holds potential for personalized treatments. Clin. Cosmet. Investig. Dermatol. 7, 207–214 (2014).
- Pochi, P. E., Strauss, J. S. & Downing, D. T. Age-related changes in sebaceous gland activity. J. Invest. Dermatol. 73, 108–111 (1979).
- Bagatin, E. et al. A randomized and controlled trial about the use of oral isotretinoin for photoaging. Int. J. Dermatol. 49, 207–214 (2010).
- Tadini, K. A., Gaspar, L. R. & Maia Campos, P. M. Epidermal effects of tretinoin and isotretinoin: Influence of isomerism. Pharmazie 61, 453–456 (2006).
- Goulden, V., Layton, A. M. & Cunliffe, W. J. Long-term safety of isotretinoin as a treatment for acne vulgaris. Br. J. Dermatol. 131, 360–3 (1994).
- Goldstein, J. A. et al. Comparative effect of isotretinoin and etretinate on acne and sebaceous gland secretion. J. Am. Acad. Dermatol. 6, 760–765 (1982).
- Rabello-Fonseca, R. et al. Oral isotretinoin in photoaging: clinical and histopathological evidence of efficacy of an off-label indication. J. Eur. Acad. Dermatol. Venereol. 23, 115–123 (2009).
- Rademaker, M. Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin. Australas. J. Dermatol. 51, 248–253 (2010).