A study of visuospatial working memory pre- and post-Gonadotropin Hormone Releasing Hormone agonists (GnRHa) in young women.
Gonadotropin Hormone Releasing Hormone agonists (GnRHa) produce an acute decline in ovarian hormone production leading to a 'pseudo' menopause. This is therapeutically useful in the management of a variety of gynaecological conditions but also serves as a powerful model to study the effects of ovarian hormones on cognition. Animal and human behavioral studies report that memory is particularly sensitive to the effects ovarian hormone suppression (e.g. post GnRHa). Further, it has recently been reported that ovariectomy in young women increases the risk of cognitive impairment in later life. However, the underlying brain networks and/or stages of memory processing that might be modulated by acute ovarian hormone suppression remain poorly understood. We used event-related fMRI to examine the effect of GnRHa on visual working memory (VWM). Neuroimaging outcomes from 17 pre-menopausal healthy women were assessed at baseline and 8 weeks after GnRHa treatment. Seventeen matched wait-listed volunteers served as the control group and were assessed at similar intervals during the late follicular phase of the menstrual cycle. We report GnRHa was associated with attenuation of left parahippocampal (BA 35) and middle temporal gyri (BA 21 ,22, 39) activation, with a significant group-by-time interaction at left precuneus (BA 7) and posterior cingulate cortex (PCC) (BA 31) at encoding, and with cerebellar activation at recognition in the context of unimpaired behavioral responses. Our study suggests that acute ovarian hormone withdrawal following GnRHa, and perhaps at other times, (e.g. following surgical menopause and postpartum) alters the neural circuitry underlying performance of VWM.
Craig
Michael C
MC
Section of Brain Maturation (PO50), Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK. m.craig@iop.kcl.ac.uk
Fletcher
Paul C
PC
Daly
Eileen M
EM
Picchioni
Marco M
MM
Brammer
Mick
M
Giampietro
Vincent
V
Rymer
Janice
J
McGuire
Philip K
PK
Maki
Pauline M
PM
Murphy
Declan G M
DG
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018231:Leiomyomatosis / Q000188:drug therapy; D008279:Magnetic Resonance Imaging; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D010364:Pattern Recognition, Visual / Q000187:drug effects* / Q000502:physiology; D011859:Radiography; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D014594:Uterine Neoplasms / Q000188:drug therapy
D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone