title: Response to flumazenil in the late luteal phase and follicular phase of the menstrual cycle in healthy control females.
abstract: BACKGROUND
  Animal studies of short-term progesterone administration and withdrawal model the natural increase and abrupt decrease in progesterone levels which occur in the late luteal phase (LP) of the human menstrual cycle (MC). Previously, studies in animals have shown that abrupt cessation of chronic or short-term progesterone administration results in pharmacological changes at the GABAA receptor, resulting in altered sensitivity to GABAA receptor neuromodulators such as benzodiazepines and flumazenil, a GABAA receptor antagonist.
  
  
  OBJECTIVE
  This study's goal was to compare the response to flumazenil in the follicular phase (FP) and late LP in female healthy controls (HCs). We postulated that HC females would exhibit a greater psychological and somatic response to flumazenil in the late LP, a period of progesterone withdrawal, compared to the FP.
  
  
  METHODS
  Twelve healthy females, without history of psychiatric disorder, were randomized to receive two injections of a 2 mg bolus injection of flumazenil (one in the late LP and one in the FP) and two injections of placebo (one in the late LP and one in the FP). Following injection, subjects were asked to rate the occurrence and intensity of panic symptoms on the panic symptom scale (PSS).
  
  
  RESULTS
  A main treatment effect was detected for the PSS score response after flumazenil injection (P=0.008). However, there was no significant treatment-by-phase interaction observed (P=0.449).
  
  
  CONCLUSIONS
  These findings indicate that MC phase did not affect the response to flumazenil in HC females. This result is contrary to our hypothesis of altered sensitivity to flumazenil in the late LP.
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Bell
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.forename: Christina
authors.initials: C
authors.lastname: Poag
authors.forename: Francois
authors.initials: F
authors.lastname: Bellavance
authors.forename: Janisse
authors.initials: J
authors.lastname: Khudabux
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Le Mellédo
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D005498:Follicular Phase / Q000187:drug effects* / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D008183:Luteal Phase / Q000187:drug effects* / Q000378:metabolism; D016584:Panic Disorder / Q000139:chemically induced; D011963:Receptors, GABA-A / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000097:blood
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid