TY - JOUR
T1 - Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS
AU - Raz, L.
AU - Hunter, L. V.
AU - Dowling, N. M.
AU - Wharton, W.
AU - Gleason, C. E.
AU - Jayachandran, M.
AU - Anderson, L.
AU - Asthana, S.
AU - Miller, V. M.
N1 - Funding Information:
The Aurora Foundation to the Kronos Longevity Research Institute, NIH HL90639, NS066147, HD65987, AG029624, P50 AG033514, UL1 RR024150 and the Mayo Foundation. Study medications for KEEPS were supplied in part by Bayer Health Care and by Abbott Pharmaceuticals. UL1 RR024150 is from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.
Publisher Copyright:
© 2015 International Menopause Society.
PY - 2016/1/2
Y1 - 2016/1/2
N2 - Background Serotonin (5-hydroxytryptamine, 5-HT) is modulated by sex steroid hormones and affects vascular function and mood. In the Kronos Early Estrogen Prevention Cognitive and Affective Ancillary Study (KEEPS-Cog), women randomized to oral conjugated equine estrogens (oCEE) showed greater benefit on affective mood states than women randomized to transdermal 17β-estradiol (tE2) or placebo (PL). This study examined the effect of these treatments on the platelet content of 5-HT as a surrogate measure of 5-HT synthesis and uptake in the brain.Methods The following were measured in a subset (n = 79) of women enrolled in KEEPS-Cog: 5-HT by ELISA, carotid intima-medial thickness (CIMT) by ultrasound, endothelial function by reactive hyperemic index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire.Results Mean platelet content of 5-HT increased by 107.0%, 84.5% and 39.8%, in tE2, oCEE and PL groups, respectively. Platelet 5-HT positively correlated with estrone in the oCEE group and with 17β- estradiol in the tE2 group. Platelet 5-HT showed a positive association with RHI, but not CIMT, in the PL and oCEE groups. Reduction in mood scores for depression-dejection and anger-hostility was associated with elevations in platelet 5-HT only in the oCEE group (r = -0.5, p = 0.02).Conclusions Effects of oCEE compared to tE2 on RHI and mood may be related to mechanisms involving platelet, and perhaps neuronal, uptake and release of 5-HT and reflect conversion of estrone to bioavailable 17β-estradiol in platelets and the brain.
AB - Background Serotonin (5-hydroxytryptamine, 5-HT) is modulated by sex steroid hormones and affects vascular function and mood. In the Kronos Early Estrogen Prevention Cognitive and Affective Ancillary Study (KEEPS-Cog), women randomized to oral conjugated equine estrogens (oCEE) showed greater benefit on affective mood states than women randomized to transdermal 17β-estradiol (tE2) or placebo (PL). This study examined the effect of these treatments on the platelet content of 5-HT as a surrogate measure of 5-HT synthesis and uptake in the brain.Methods The following were measured in a subset (n = 79) of women enrolled in KEEPS-Cog: 5-HT by ELISA, carotid intima-medial thickness (CIMT) by ultrasound, endothelial function by reactive hyperemic index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire.Results Mean platelet content of 5-HT increased by 107.0%, 84.5% and 39.8%, in tE2, oCEE and PL groups, respectively. Platelet 5-HT positively correlated with estrone in the oCEE group and with 17β- estradiol in the tE2 group. Platelet 5-HT showed a positive association with RHI, but not CIMT, in the PL and oCEE groups. Reduction in mood scores for depression-dejection and anger-hostility was associated with elevations in platelet 5-HT only in the oCEE group (r = -0.5, p = 0.02).Conclusions Effects of oCEE compared to tE2 on RHI and mood may be related to mechanisms involving platelet, and perhaps neuronal, uptake and release of 5-HT and reflect conversion of estrone to bioavailable 17β-estradiol in platelets and the brain.
KW - 17β-estradiol
KW - 5-hydroxytryptamine
KW - Conjugated equine estrogen
KW - Kronos Early Estrogen Prevention Study
KW - platelet
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U2 - 10.3109/13697137.2015.1116504
DO - 10.3109/13697137.2015.1116504
M3 - Article
C2 - 26652904
AN - SCOPUS:84954028100
SN - 1369-7137
VL - 19
SP - 49
EP - 59
JO - Climacteric
JF - Climacteric
IS - 1
ER -