Serum gonadal steroid reactivity to acute psychosocial stress in panic disorder patients

Knowledge on the hypothalamic-pituitary-gonadal (HPG) axis reactivity to acute psychosocial stress remains limited. The current study evaluated whether testosterone, progesterone, and estradiol increase in response to the Trier Social Stress Test (TSST), and whether these responses are attenuated in panic disorder (PD) patients compared to healthy controls (HC), given the reported hypothalamic-pituitary-adrenal (HPA) axis hyporesponsiveness in PD. Two sex- and age-matched groups (n = 30 HC, n = 30 PD; n = 19 women and n = 11 men per group) underwent the TSST. Serum gonadal steroids were measured 15 min pre- and 1, 10, and 20 min post-TSST. Mixed models revealed significant post-TSST increases in testosterone (F(3, 174) = 5.43, p = .001) and progesterone (F(3, 168) = 5.39, p = .002), but not in estradiol (F(3, 169) = 2.52, p = .06). PD patients displayed higher estradiol levels than HCs (F(1, 56) = 10.11, p = .002). Men showed higher testosterone (F(1, 57) = 675.89, p < .001) and lower progesterone (F(1, 56) = 5.38, p = .024) than women. Exploratory analyses suggested distinct temporal patterns across groups for all three gonadal steroids. These findings indicate a potential role of gonadal steroids in psychosocial stress regulation and highlight its relevance as an understudied mechanism in panic disorder. Potential factors masking main effects and interactions such as interindividual variability and sex imbalances are discussed. Future studies including larger, more sex-balanced samples are needed to clarify these patterns.