A large population analysis has found no clinically meaningful reduction in adult height among teenagers treated with isotretinoin, despite longstanding concerns over premature growth plate closure.
Fears that isotretinoin treatment during adolescence could stunt growth appear unsupported by new evidence from one of the largest studies yet conducted on the issue, with Danish researchers finding no clinically meaningful association between acne treatment and reduced adult height.
The nationwide cross-sectional study, published in JAMA Dermatology, analysed data from 379,196 adolescents and young adults with acne who underwent military conscription assessments in Denmark between 2001 and 2015.
Researchers linked conscription height measurements with national prescription and hospital registries to examine whether isotretinoin exposure before adulthood affected final linear growth.
The findings directly address a longstanding concern surrounding isotretinoin, a highly effective therapy for moderate to severe acne that has carried warnings about potential skeletal effects for decades.
Retinoic acid influences endochondral ossification pathways, and isolated case reports have described premature epiphyseal closure in adolescents treated with retinoids, particularly at high oncologic doses.
But in the Danish cohort, isotretinoin users reached virtually identical adult heights to peers without acne treatment exposure.
Among men, the adjusted mean difference in adult height compared with the no-acne reference group was 0.31 cm (95% CI, 0.20-0.41 cm). Among women, the adjusted difference was 0.25 cm (95% CI, −0.47 to 0.96 cm).
Both estimates fell far below the study’s predefined threshold of 5cm for clinical significance.
The analysis included 16,739 male isotretinoin users and 278 female users. Mean adult height among isotretinoin-treated participants was 180.6cm in men and 168.3cm in women, closely mirroring heights recorded among participants treated with prolonged tetracycline therapy for acne.
The researchers also examined whether earlier treatment exposure during puberty altered outcomes.
In boys who initiated isotretinoin before age 13 years, adjusted adult height was approximately 1.7cm lower than the reference population, while boys beginning treatment at age 13 years were around 1.8cm shorter.
However, the authors emphasised these differences remained well below the prespecified threshold for clinical relevance and may reflect normal biological variation or confounding factors linked to acne severity and pubertal timing.
No significant differences were identified among girls treated before age 15 years, although the number of female participants treated at very young ages was small, limiting statistical precision, the researchers noted.
Importantly, they found no evidence of a dose-response relationship between cumulative isotretinoin exposure and adult height.
Even participants receiving higher cumulative doses showed no clinically meaningful reduction in final stature, including analyses restricted to treatment before age 15 years.
The study also evaluated stunting as a secondary outcome. Among male participants, isotretinoin users actually demonstrated a slightly lower prevalence of stunting than the no-acne group, although absolute differences were small.
The researchers said the results strengthened a limited but growing evidence base suggesting isotretinoin did not adversely affect ultimate growth outcomes.
Related
Earlier studies from the United States and analyses using TriNetX data similarly failed to identify reduced adult height among isotretinoin users, although those studies were considerably smaller and lacked detailed dose-response analyses.
“Our study extends this evidence base by incorporating detailed analyses of both age at treatment initiation and cumulative isotretinoin dose,” the researchers wrote.
“Neither analysis suggested an adverse association, and all estimates compatible with our data were smaller than the prespecified 5-cm threshold for clinical relevance.
“Even if a 3cm reduction in adult height were considered clinically relevant, our findings would not support an adverse association.
“However, the minimally important difference in height is inherently context dependent and may vary between individuals, which should be considered in shared decision-making between clinicians and patients.”
The researchers acknowledged several limitations, including the relatively small number of younger female isotretinoin users and the absence of repeated anthropometric measurements that could assess transient changes in growth velocity during adolescence.
They also noted the findings may not apply to prolonged high-dose retinoid regimens used in oncology or severe keratinisation disorders.
Despite this, they concluded the data should reassure clinicians, patients and families considering isotretinoin for moderate to severe acne during adolescence.
“Given the substantial psychosocial burden of moderate to severe acne, these findings may provide reassurance for clinicians, patients, and families and support shared evidence-based decision-making when isotretinoin therapy is considered during adolescence,” the researchers concluded.
