Study Reveals Key Biochemical Risks of Isotretinoin in Acne Treatment

A new five-year retrospective analysis has reinforced isotretinoin’s reputation as the gold standard for severe acne—while also shedding light on several underappreciated biochemical risks associated with its use. Published in the Journal of Clinical Medicine, the study evaluated 370 patients treated between 2020 and 2025 and offers one of the most detailed real-world portraits of isotretinoin’s safety profile to date.

Oral isotretinoin has been a cornerstone of dermatologic care for more than four decades. Its ability to shrink sebaceous glands and normalize keratinocyte turnover makes it uniquely effective against acne that fails to respond to conventional therapy. Yet, its potency comes with a well-known constellation of side effects, from dryness and photosensitivity to teratogenicity.

The Polish research team, led by Dr. Igor Jarosław Feszak of the Pomeranian University in Słupsk, sought to quantify how often these effects occur in routine practice and to what degree they correlate with dose, age, and biochemical parameters.

Among the cohort—whose average age was 28 years—skin dryness (xerosis) was the most common complaint, affecting 70% of patients. Retinoid dermatitis occurred in one in five participants, while cheilitis, or inflammation of the lips, affected 15.5%. Other cutaneous effects such as pruritus (8.4%) and hand eczema (3.5%) were comparatively rare.

Interestingly, the study found subtle but significant links between dosing and symptom patterns: higher daily isotretinoin doses correlated with more frequent hand eczema, while higher cumulative doses were paradoxically associated with less itching. Younger patients were more prone to retinoid dermatitis, whereas older individuals experienced more skin peeling.

While mucocutaneous symptoms remain expected, the study’s most notable finding lay in its metabolic data. Compared with age- and sex-matched controls, patients on isotretinoin were twice as likely to develop dyslipidemia overall. LDL cholesterol rose more than threefold, triglycerides nearly doubled, and HDL cholesterol decreased significantly.

Perhaps the study’s most surprising observation was an eightfold increase in elevated prolactin levels among isotretinoin users compared with controls. This finding diverges from earlier literature, which has typically shown decreased prolactin during treatment.

In contrast to its lipid and endocrine impacts, isotretinoin’s influence on liver and thyroid function appeared limited. Although mild elevations in aminotransferases (AST and ALT) were observed, these changes did not reach statistical significance. Similarly, while TSH levels were 1.5 times higher among treated patients, this difference was not significant, echoing prior findings that true hepatotoxicity or hypothyroidism remains uncommon with standard dosing.

While isotretinoin continues to offer unparalleled efficacy for acne vulgaris, the findings from this Polish cohort reinforce the drug’s need for careful metabolic surveillance. Lipid monitoring should remain routine, and clinicians may wish to broaden endocrine vigilance, especially in patients exhibiting hormonal symptoms.