Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS

L. Raz, L. V. Hunter, N. M. Dowling, W. Wharton, C. E. Gleason, M. Jayachandran, L. Anderson, S. Asthana, Virginia M Miller

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)49-59
Number of pages11
JournalClimacteric
Volume19
Issue number1
DOIs
StatePublished - Jan 2 2016

Fingerprint

Blood Vessels
Serotonin
Conjugated (USP) Estrogens
Hormones
Blood Platelets
Therapeutics
Estradiol
Estrone
Placebos
Affective Symptoms
Hostility
Anger
Brain
Gonadal Steroid Hormones
Estrogens
Enzyme-Linked Immunosorbent Assay
Depression

Keywords

  • 17β-estradiol
  • 5-hydroxytryptamine
  • Conjugated equine estrogen
  • Kronos Early Estrogen Prevention Study
  • platelet

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Raz, L., Hunter, L. V., Dowling, N. M., Wharton, W., Gleason, C. E., Jayachandran, M., ... Miller, V. M. (2016). Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS. Climacteric, 19(1), 49-59. https://doi.org/10.3109/13697137.2015.1116504

Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS. / Raz, L.; Hunter, L. V.; Dowling, N. M.; Wharton, W.; Gleason, C. E.; Jayachandran, M.; Anderson, L.; Asthana, S.; Miller, Virginia M.

In: Climacteric, Vol. 19, No. 1, 02.01.2016, p. 49-59.

Research output: Contribution to journalArticle

Raz, L, Hunter, LV, Dowling, NM, Wharton, W, Gleason, CE, Jayachandran, M, Anderson, L, Asthana, S & Miller, VM 2016, 'Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS', Climacteric, vol. 19, no. 1, pp. 49-59. https://doi.org/10.3109/13697137.2015.1116504
Raz L, Hunter LV, Dowling NM, Wharton W, Gleason CE, Jayachandran M et al. Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS. Climacteric. 2016 Jan 2;19(1):49-59. https://doi.org/10.3109/13697137.2015.1116504
Raz, L. ; Hunter, L. V. ; Dowling, N. M. ; Wharton, W. ; Gleason, C. E. ; Jayachandran, M. ; Anderson, L. ; Asthana, S. ; Miller, Virginia M. / Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS. In: Climacteric. 2016 ; Vol. 19, No. 1. pp. 49-59.
@article{5caf19dbf4844adb8206667398f1459b,
title = "Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS",
abstract = "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.",
keywords = "17β-estradiol, 5-hydroxytryptamine, Conjugated equine estrogen, Kronos Early Estrogen Prevention Study, platelet",
author = "L. Raz and Hunter, {L. V.} and Dowling, {N. M.} and W. Wharton and Gleason, {C. E.} and M. Jayachandran and L. Anderson and S. Asthana and Miller, {Virginia M}",
year = "2016",
month = "1",
day = "2",
doi = "10.3109/13697137.2015.1116504",
language = "English (US)",
volume = "19",
pages = "49--59",
journal = "Climacteric",
issn = "1369-7137",
publisher = "Informa Healthcare",
number = "1",

}

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, Virginia M

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

UR - http://www.scopus.com/inward/record.url?scp=84954028100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954028100&partnerID=8YFLogxK

U2 - 10.3109/13697137.2015.1116504

DO - 10.3109/13697137.2015.1116504

M3 - Article

C2 - 26652904

AN - SCOPUS:84954028100

VL - 19

SP - 49

EP - 59

JO - Climacteric

JF - Climacteric

SN - 1369-7137

IS - 1

ER -