title: ACTH and cortisol response to Dex/CRH testing in women with and without premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian steroid replacement.
abstract: BACKGROUND
  During conditions of ovarian suppression, women with premenstrual dysphoria (PMD) experience abnormal behavioral responses to physiological levels of ovarian steroids. Although hypothalamic-pituitary-adrenal (HPA) axis dysregulation frequently accompanies depression, and ovarian steroids regulate HPA axis responsivity, the role of HPA axis dysregulation in PMD is not known. We hypothesized that women with PMD would show abnormalities of HPA axis function analogous to those reported in depressive illness, and that ovarian steroids would differentially regulate HPA axis function in women with PMD compared with asymptomatic controls (AC).
  
  
  OBJECTIVE
  Our objective was to characterize the HPA axis response to physiological levels of estradiol and progesterone in women with PMD and AC.
  
  
  METHODS
  We conducted an open-label trial of the GnRH agonist depot Lupron with ovarian steroid replacement administered in a double-blind crossover design in an outpatient clinic.
  
  
  METHODS
  Forty-three women (18 with prospectively confirmed PMD and 25 AC) participated.
  
  
  METHODS
  Women received Lupron for 6 months. After 3 months of hypogonadism, women received 5 wk each of estradiol (100-μg patch daily) or progesterone (suppositories 200 mg twice daily). During each condition, combined dexamethasone-suppression/CRH-stimulation tests and 24-h urinary free cortisol levels were performed.
  
  
  METHODS
  Plasma cortisol and ACTH levels were evaluated.
  
  
  RESULTS
  HPA axis function was similar in PMD compared with AC. In all, progesterone significantly increased the secretion of cortisol compared with estradiol [area under the curve (t(74) = 3.1; P < 0.01)] and urinary free cortisol (t(74) = 3.2; P < 0.01) and ACTH compared with hypogonadism [area under the curve (t(74) = 2.4; P < 0.05)].
  
  
  CONCLUSIONS
  HPA axis regulation is normal in PMD, suggesting that the pathophysiology of PMD differs from major depression. As observed previously, progesterone but not estradiol up-regulates HPA axis function in women.
authors.affiliation: Section on Behavioral Endocrinology, National Institute of Mental Health, Bethesda, Maryland 20892-1277, USA.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Lee
authors.forename: Lynnette K
authors.initials: LK
authors.lastname: Nieman
authors.forename: Pedro E
authors.initials: PE
authors.lastname: Martinez
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Harsh
authors.forename: David R
authors.initials: DR
authors.lastname: Rubinow
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D018592:Cross-Over Studies; D003907:Dexamethasone; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage; D005938:Glucocorticoids; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007006:Hypogonadism / Q000097:blood / Q000139:chemically induced*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D016729:Leuprolide / Q000008:administration & dosage*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D011293:Premenstrual Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011374:Progesterone / Q000008:administration & dosage* / Q000097:blood; D055815:Young Adult
chemical_list: D005300:Fertility Agents, Female; D005938:Glucocorticoids; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D016729:Leuprolide; D006854:Hydrocortisone