Jenifer Sassarini1, Rajeev Krishnadas2, Jonathan Cavanagh2, Alice Nicol3, Sally L Pimlott4, William Ferrell5, Mary Ann Lumsden6. 1. Obstetrics and Gynaecology, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, G11 6NT, United Kingdom. Electronic address: jenifer.sassarini@glasgow.ac.uk. 2. Sackler Institute of Psychobiological Research, Institute of Health and Wellbeing, Southern General Hospital, Glasgow G51 4TF, United Kingdom. 3. Nuclear Medicine Department, South Glasgow, NHS Greater Glasgow and Clyde, United Kingdom. 4. West of Scotland Radionuclide Dispensary, University of Glasgow and Greater Glasgow and Clyde NHS Trust, Glasgow G11 6NT, United Kingdom. 5. Institute of Infection, Immunity and Inflammation, University of Glasgow, G11 6NT, United Kingdom. 6. Obstetrics and Gynaecology, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, G11 6NT, United Kingdom.
Abstract
BACKGROUND: Although 70% of postmenopausal women suffer from hot flashes the pathophysiology is poorly understood. The serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine provides relief of flushing although the mechanism is unknown and could involve a central effect and/or a peripheral effect. Using single photon emission computed tomography (SPECT) we studied the central serotonin transporter (SERT) in vivo using [(123)I]-beta-carbomethoxy-3-β-(4-iodophenyl)tropane (beta-CIT) and, as previous studies have shown that reactivity of the skin blood vessels is enhanced in those who flush, we examined cutaneous microvascular perfusion. METHODS: Cutaneous microvascular perfusion was assessed in 31 postmenopausal women, with flushing, using laser Doppler imaging with iontophoresis (LDI+ION), before and after 8 weeks of treatment with venlafaxine. A sub-group of 14 of these women also had SPECT imaging at both time points to evaluate the availability of SERT in the brain. Flush frequency and score was recorded, and Beck Depression Inventory (BDI) II scores were assessed before and after treatment. RESULTS: Following treatment with venlafaxine, there was a significant reduction in the [(123)I]-beta-CIT binding ratio, BDI scores, flushing and endothelial dependent perfusion response. [(123)I]-Beta-CIT reduction was associated with BDI reduction (r(2)=0.54; F=8.8; p=0.004), but not flushing reduction or perfusion reduction. CONCLUSIONS: Venlafaxine resulted in a decrease in BDI II scores with an associated reduction in [(123)I]-beta-CIT binding in a group of non-depressed women. It also improved flush frequency and severity which may be as a result of decreases seen in enhanced cutaneous microvascular perfusion.
BACKGROUND: Although 70% of postmenopausal women suffer from hot flashes the pathophysiology is poorly understood. The serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine provides relief of flushing although the mechanism is unknown and could involve a central effect and/or a peripheral effect. Using single photon emission computed tomography (SPECT) we studied the central serotonin transporter (SERT) in vivo using [(123)I]-beta-carbomethoxy-3-β-(4-iodophenyl)tropane (beta-CIT) and, as previous studies have shown that reactivity of the skin blood vessels is enhanced in those who flush, we examined cutaneous microvascular perfusion. METHODS: Cutaneous microvascular perfusion was assessed in 31 postmenopausal women, with flushing, using laser Doppler imaging with iontophoresis (LDI+ION), before and after 8 weeks of treatment with venlafaxine. A sub-group of 14 of these women also had SPECT imaging at both time points to evaluate the availability of SERT in the brain. Flush frequency and score was recorded, and Beck Depression Inventory (BDI) II scores were assessed before and after treatment. RESULTS: Following treatment with venlafaxine, there was a significant reduction in the [(123)I]-beta-CIT binding ratio, BDI scores, flushing and endothelial dependent perfusion response. [(123)I]-Beta-CIT reduction was associated with BDI reduction (r(2)=0.54; F=8.8; p=0.004), but not flushing reduction or perfusion reduction. CONCLUSIONS:Venlafaxine resulted in a decrease in BDI II scores with an associated reduction in [(123)I]-beta-CIT binding in a group of non-depressed women. It also improved flush frequency and severity which may be as a result of decreases seen in enhanced cutaneous microvascular perfusion.
Authors: Tom G Bailey; N Timothy Cable; Nabil Aziz; Greg Atkinson; Daniel J Cuthbertson; David A Low; Helen Jones Journal: J Physiol Date: 2015-12-30 Impact factor: 5.182