title: Sex-related differences in stimulated hypothalamic-pituitary-adrenal axis during induced gonadal suppression.
abstract: BACKGROUND
  Sex-related differences in the stress response are well described in the animal literature but in humans are inconsistent and appear to reflect both the method used to stimulate the hypothalamic-pituitary-adrenal (HPA) axis and the age of the subjects. Sex-related differences in reproductive steroid levels further confound efforts to define the specific role of the sex of the individual in stress axis responsivity.
  
  
  OBJECTIVE
  The aim of this study was to address this role independent of differences in reproductive steroid levels. We compared HPA axis response to pharmacological (CRH) and physiological (exercise) stressors in two groups of young to middle-aged (18-45 yr) men (n = 10 and 8) and women (n = 12 and 13) undergoing gonadal suppression with leuprolide acetate (monthly im injection of 7.5 mg in men and 3.75 mg in women).
  
  
  METHODS
  Exercise and CRH stimulation tests were performed during induced hypogonadal conditions.
  
  
  METHODS
  The study was conducted at a National Institutes of Health Clinical Center Outpatient Clinic. PATIENT OR OTHER PARTICIPANTS: Male and female normal volunteers participated in the study.
  
  
  METHODS
  The main outcome measures were stimulated ACTH and cortisol levels.
  
  
  RESULTS
  Both CRH (1 microg/kg) stimulation and graded treadmill exercise stimulation occurred in the month after the second leuprolide injection to ensure gonadal suppression. Despite the absence of sex differences in estradiol or testosterone at the time of testing, men showed increased stimulated ACTH (repeated-measures ANOVA for CRH, P < 0.005) and cortisol (repeated-measures ANOVA for exercise, P < 0.05) compared with women. Among the summary measures, area under the curve (AUC) for cortisol was significantly greater in men than women after exercise. Although the AUC for ACTH was not significantly different across sexes, the initial AUC (0-30 min) was significantly greater in men for both procedures. No significant sex differences were found in a measure of adrenal responsivity, the cortisol to ACTH ratio, for either procedure. Cortisol-binding globulin levels did not differ between men and women and were not correlated with stimulated HPA axis measures. These data confirm earlier reports of sex differences in stimulated HPA axis activity and demonstrate that these differences exist even under induced hypogonadal conditions (i.e. in the absence of characteristic differences in reproductive steroids).
authors.affiliation: Office of Special Populations, National Institute of Mental Health, Rockville, Maryland 20857, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Roca
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schmidt
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Deuster
authors.forename: Merry A
authors.initials: MA
authors.lastname: Danaceau
authors.forename: Margaret
authors.initials: M
authors.lastname: Altemus
authors.forename: Karen
authors.initials: K
authors.lastname: Putnam
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Lynnette K
authors.initials: LK
authors.lastname: Nieman
authors.forename: David R
authors.initials: DR
authors.lastname: Rubinow
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002352:Carrier Proteins / Q000032:analysis; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D015444:Exercise; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012727:Sex Characteristics
chemical_list: D002352:Carrier Proteins; C027091:cortisol binding globulin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone