Hair cortisol/cortisone in combined oral contraceptive users: An exploratory analysis

Contraception. 2025 Nov 20:111310. doi: 10.1016/j.contraception.2025.111310. Online ahead of print.

Abstract

Objective: To determine whether combined oral contraceptives (COCs) containing ethinyl estradiol and drospirenone are associated with higher chronic biological stress, indicated by hair cortisol and cortisone, among White South African women.

Methods: In this cross-sectional study, proximal hair segments (1 cm) from COC users (n = 24) and non-users (n = 24) were analyzed by LC-MS/MS.

Results: No significant group differences were observed for hair cortisol (median 2.22 vs 2.59 pg/mg), cortisone (6.58 vs 6.95 pg/mg), total glucocorticoids (8.66 vs 8.98 pg/mg), or cortisol/cortisone ratio (0.38 vs 0.38). In controls, cortisol and cortisone correlated negatively with age and sample storage time. Excluding women with hair treatments revealed modestly higher glucocorticoids in COC users (effect size ≈ 0.3) and stronger correlations with BMI and body fat, suggesting such treatments may mask glucocorticoid signals.

Conclusion: COC use was not associated with higher hair glucocorticoids, though hair treatments may influence detection.

Implications: These findings suggest that COC use does not increase hair glucocorticoid levels, while underscoring the need to consider hair treatments as a potential confounder in biomarker-based stress assessments.

Keywords: Chronic stress; Combined oral contraceptives; Cortisone; Drospirinone; Hair cortisol; LC-MS/MS.