Effects of excessive topical glucocorticoids on ovarian aging

Glucocorticoid drugs (GCs) are widely used in dermatology due to their potent anti-inflammatory and immunosuppressive effects. While numerous studies have demonstrated that exposure to glucocorticoids-whether due to stress or exogenous administration-can lead to severe ovarian aging, direct evidence regarding whether topical glucocorticoid (GC) treatment for dermatologic conditions affects ovarian aging remains limited. In female C57BL/6 mice (n = 6 per group), we established an excessive topical GC exposure model using an intentionally supratherapeutic fluocinolone acetonide regimen, which caused marked epidermal/dermal atrophy and impaired skin barrier function. Skin injury was evaluated by histological and barrier-marker assessments, and ovarian aging was assessed by estrous cyclicity, follicle counts, ovarian fibrosis, and the expression of AMH, p16INK4a, and γH2AX. In the present study, exogenous GCs caused marked atrophy in both the epidermal and dermal layers of the skin, impairing skin barrier function. These findings suggest that the dosage administered exceeded the therapeutic range, resulting in severe skin aging. However, the estrous cycles of the mice remained normal, and there were no significant differences in ovarian follicle counts, tissue fibrosis, or the protein expression of AMH, p16^INK4a, and γH2AX compared to the control group. Under the specific experimental conditions tested, no significant ovarian aging-related differences were detected. However, systemic glucocorticoid exposure was not measured, and the study was not powered to exclude small effects on ovarian function. Therefore, these findings do not establish ovarian safety, and larger and longer-duration studies are required.