Central obesity, depression and the hypothalamo - pituitary - adrenal axisin men and postmenopausal women

OBJECTIVE: We examined the relationship of adiposity to pituitary-adrenal r esponses to corticotrophin-releasing hormone (CRH) in men and postmenopausa l women, controlling for the influence of depression. DESIGN: Studies of CRH responses, cortisol metabolite levels and depression scores in relation to adiposity in men and postmenopausal women. SUBJECTS: Thirteen men: age (median, interquartile range) 62 y (52-63), bod y mass index (BMI) 29.0 kg/m(2) (26.3-33.1), waist circumference (waist) 10 5 cm (97-111), waist:hip ratio (WHR) 1.03 (0.98-1.07), subscapular to trice ps skinfold thickness ratio (STR) 2.0 (1.2-2.4), total body fat (TBF) 25.4 kg (19.8-28.8); and eight women: age 54 y (53-62), BMI 30 kg/m(2) (23-41), waist 86 cm (79-117), WHR 0.94 (0.87-1.10), STR 1.0 (0.85-1.07), TBF 35.0 k g (18.7-48.8). MEASUREMENTS: A standard CRH test was conducted with additional basal sampl es taken for leptin and interleukin 6 (IL-6). Total urine cortisol metaboli tes (TCM) and the ratio of urinary cortisol:cortisone (Fm/Em) metabolites w ere measured. Depression scores were measured by the General Health Questio nnaire (GHQ-30) and Hospital Anxiety and Depression Scale (HAD) questionnai re. All subjects completed an overnight dexamethasone suppression test. RESULTS: The basal to peak percentage increments (%inc.) in adrenocorticotr ophic hormone (ACTH) and cortisol in men correlated directly with SIR (ACTH %inc. r = 0.70, P < 0.01; cortisol %inc. r = 0.55, P = 0.05); this relatio nship was independent of depression scores. In women, the ACTH area under i ncremental curve (AUIC) correlated negatively with STR (r = -0.81, P(0.05). In men, but not in women, there was a significant correlation between GHQ- 30 score and ACTH AUIC (r = 0.62, P < 0.05) and cortisol AUIC (r = 0.72, P < 0.01). Depression scores were consistently and directly related to indice s of obesity and central obesity. There were no significant relationships i n either sex between urinary TCM or Fm/Em ratio and BMI, waist, WHR, TBF, S TR or CRH responses. The urinary Fm/Em ratio was higher in men than in wome n (median 0.74 vs 0.66, P < 0.05). In men, but not in women, GHQ-30 scores correlated positively with urinary TCM (r = 0.57, P = 0.05) and HAD-depress ion scores were inversely related to the urine Fm/Em ratio (r = -0.65, P < 0.05). All subjects suppressed normally with dexamethasone. CONCLUSIONS: Cortisol metabolite levels were increased in depression in men , but were not related to adiposity in either sex. We demonstrate that cent ral obesity in men, but not postmenopausal women, is associated with an enh anced pituitary-adrenal response to CRH and that this relationship is indep endent of depression score.