title: Gonadotropin hormone releasing hormone agonists alter prefrontal function during verbal encoding in young women.
abstract: Gonadotropin hormone releasing hormone agonists (GnRHa) are commonly used in clinical practice to suppress gonadal hormone production in the management of various gynaecological conditions and as a treatment for advanced breast and prostate cancer. Animal and human behavioural studies suggest that GnRHa may also have significant effects on memory. However, despite the widespread use of GnRHa, the underlying brain networks and/or stages of memory processing that might be modulated by GnRHa remain poorly understood. We used event-related functional magnetic resonance imaging to examine the effect of GnRHa on verbal encoding and retrieval. Neuroimaging outcomes from 15 premenopausal healthy women were assessed at baseline and 8 weeks after Gonadotrophin Releasing Hormone analogue (GnRHa) treatment. Fifteen matched wait-listed volunteers served as the control group and were assessed at similar intervals during the late follicular phase of the menstrual cycle. GnRHa was associated with changes in brain response during memory encoding but not retrieval. Specifically, GnRHa administration led to a change in the typical pattern of prefrontal activation during successful encoding, with decreased activation in left prefrontal cortex, anterior cingulate, and medial frontal gyrus. Our study suggests that the memory difficulties reported by some women following GnRHa, and possibly at other times of acute ovarian hormone withdrawal (e.g. following surgical menopause and postpartum), may have a clear neurobiological basis; one that manifest during encoding of words and that is evident in decreased activation in prefrontal regions known to sub-serve deep processing of to-be-learned words.
authors.affiliation: Section of Brain Maturation (PO50), Department of Psychological Medicine, Institute of Psychiatry, 16 De Crespigny Park, Denmark Hill, London SE5 8AF, UK. m.craig@iop.kcl.ac.uk
authors.forename: Michael C
authors.initials: MC
authors.lastname: Craig
authors.forename: Paul C
authors.initials: PC
authors.lastname: Fletcher
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Daly
authors.forename: Janice
authors.initials: J
authors.lastname: Rymer
authors.forename: William J
authors.initials: WJ
authors.lastname: Cutter
authors.forename: Mick
authors.initials: M
authors.lastname: Brammer
authors.forename: Vincent
authors.initials: V
authors.lastname: Giampietro
authors.forename: Harvey
authors.initials: H
authors.lastname: Wickham
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Maki
authors.forename: Declan G M
authors.initials: DG
authors.lastname: Murphy
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000494:pharmacology*; D006728:Hormones / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects; D014705:Verbal Behavior / Q000187:drug effects*
chemical_list: D006728:Hormones; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone