Psychoneuroendocrinology 26 (2001) 493–502 www.elsevier.com/locate/psyneuen Prolactin response to d-fenﬂuramine in postmenopausal women on and off ERT: comparison with young women Therese A.M.J. van Amelsvoort a,* , Kathryn M. Abel a , Dene M.R. Robertson a , Eileen Daly a , Hugo Critchley a , Malcolm Whitehead b , Declan G.M. Murphy a a Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK b Menopause Clinic, King’s College Hospital, London, UK Received 20 July 2000; received in revised form 21 December 2000; accepted 22 December 2000 Abstract Estrogen is thought to have an impact on both psychological well being and cognitive func- tion. The biological basis to this is not fully understood, but may involve estrogen’s interac- tions with central serotonergic (5-HT) systems. Therefore, we studied the effect of long-term estrogen hormone replacement therapy (ERT) on central 5-HT tone in healthy postmenopausal women and made comparisons with young women. Prolactin (PRL) responses to the speciﬁc 5-HT releasing and re-uptake inhibiting agent, d-fenﬂuramine, were measured in three groups of healthy women: 11 young, 11 postmenopausal on long-term ERT, and 11 postmenopausal ERT naı ¨ve. PRL responses were signiﬁcantly decreased in ERT naı ¨ve women compared to young healthy women. In contrast, PRL responses were not different between estrogen-treated and young women. Overall, there was a signiﬁcant relationship between older age and lower PRL responsivity. These results suggest that central 5-HT tone is reduced in healthy postmeno- pausal women who are ERT naı ¨ve, but not in postmenopausal women who have received prolonged estrogen treatment. Estrogen may modulate age-related changes in 5-HT tone. This may partly explain why estrogen can decrease vulnerability to mood disorders and cognitive changes in postmenopausal women.  2001 Elsevier Science Ltd. All rights reserved. Keywords: Serotonin; Estrogen; Menopause; Ageing; Gender * Corresponding author: Tel.: +44-20-7848-0785; fax: +44-20-7848-0650. E-mail address: spjutva@iop.kcl.ac.uk (T.A.M.J. van Amelsvoort). 0306-4530/01/$ - see front matter  2001 Elsevier Science Ltd. All rights reserved. PII:S0306-4530(01)00008-7