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, V. M. Miller

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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
Issue number1
StatePublished - Jan 2 2016


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

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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