Cortisol response to d-fenfluramine in patients with obsessive-compulsive disorder and in healthy subjects: evidence for a gender-related effect

In order to evaluate serotonergic function in obsessive-compulsive disorder (OCD), plasma cortisol response to d-fenfluramine (30 mg p.o.) was examined in 20 drug-free obsessive-compulsive patients (10 males and 10 females) and in 20 age- and sex-matched healthy subjects, under double-blind, placebo-controlled conditions. We found that: (a) baseline plasma cortisol secretion was significantly increased in patients with OCD; (b) in healthy subjects, the cortisol response to d-fenfluramine was evident in women, but no in men, (c) plasma cortisol response to the serotonergic challenge did not differ between patients and controls, but it was significantly reduced in female patients as compared to healthy women. These results demonstrate a hyperactivity of the hypothalamo-pituitary-adrenal axis in obsessive-compulsive patients and suggest a dysfunction of 5-HT transmission in female patients.