Depression in premenopausal women: gonadal hormones and serotonergic system assessed by D-fenfluramine challenge test

Purpose: The aim of the study was to compare the activity of gonadal hormones and serotonergic system in premenopausal women with or without depression in relation to clinical and hormonal indices of menopause. Methods: The sample included 60 women with single or recurrent major depressive episode with disease onset after 38 year of age (mean age 43 years) and 30 healthy control women (mean age 41 years). Psychometric assessment was done by means of 17-item Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI). The presence of menopausal symptoms was assessed by Kupperman Menopause Index (KMI). Activity of gonadal axis was measured by estimating estradiol and follicle-stimulating hormone (FSH) levels. For the assessment of central serotonergic activity, the D-fenfluramine test was used. Results: Depressed women had higher intensity of menopausal symptoms, significantly lower concentration of estradiol, and higher of FSH than control women. Severity of depression correlated with both the intensity of menopausal symptoms and the concentration of FSH. Baseline levels of prolactin were not different in both groups. Following D-fenfluramine administration, there was a significant increase in prolactin concentration in healthy women and a transient decrease in depressed ones. Baseline cortisol level was significantly higher in depressed women and correlated with the severity of depression. D-Fenfluramine challenge caused a significant increase of cortisol secretion in healthy women and a significant decrease in depressed ones. A relationship was observed between baseline estradiol, FSH, and cortisol level and the magnitude of prolactin and cortisol response to D-fenfluramine. Conclusions: In premenopausal women, a high degree of interconnections was demonstrated between symptoms of depression and symptoms of menopause on both clinical and hormonal level. The results confirm the association between depressive and menopausal symptoms as well as an involvement of gonadal hormones, cortisol, and serotonin deficiency in this process. (C) 2003 Elsevier Science Inc. All rights reserved.