Association of baseline peripheral sex hormone profiles and metabolic parameters with recurrence after oral isotretinoin treatment in patients with severe acne.

Background: Acne recurrence after oral isotretinoin remains common, but the clinical, treatment-related, hormonal, and metabolic factors associated with recurrence are not well defined. Methods: This retrospective cohort study included 351 patients (185 males and 166 females) with severe acne who received oral isotretinoin treatment between April 2021 and April 2025. Patients were classified into recurrence and non-recurrence groups according to follow-up outcomes after isotretinoin discontinuation. Baseline demographic characteristics, acne-related clinical features, isotretinoin treatment variables, peripheral sex hormone profiles, and metabolic parameters were collected. Univariate and multivariable logistic regression analyses were used to identify factors associated with recurrence. The combined prediction model was derived from the final multivariable logistic regression model and subsequently evaluated using receiver operating characteristic curve analysis, calibration assessment, and bootstrap internal validation. Results: During a median follow-up of 20.0 months, 91 patients developed recurrence, with an overall recurrence rate of 25.9%. Multivariate analysis showed that longer disease duration, lower cumulative isotretinoin dose, higher free androgen index, higher dehydroepiandrosterone sulfate, lower sex hormone-binding globulin, higher homeostatic model assessment of insulin resistance, higher triglyceride levels, and lower high-density lipoprotein cholesterol were independently associated with recurrence. Individual hormonal and metabolic indicators showed limited discriminatory ability. The combined prediction model demonstrated better performance, with an area under the curve of 0.824, sensitivity of 76.9%, and specificity of 76.2%. Bootstrap internal validation yielded a corrected area under the curve of 0.812. Conclusions: Individual hormonal and metabolic markers had limited discriminatory value, whereas a combined model integrating disease duration, cumulative isotretinoin dose, free androgen index, dehydroepiandrosterone sulfate, sex hormone-binding globulin, HOMA-IR, triglycerides, and high-density lipoprotein cholesterol showed better internal performance. Because cumulative dose becomes available during treatment, the model is best regarded as an exploratory dynamic risk-stratification tool; external prospective validation and a clearly defined management pathway are required before routine clinical use.