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.
authors.affiliation: a Department of Physiology and Biomedical Engineering , Mayo Clinic , Rochester , Minnesota , USA ;
authors.forename: L
authors.initials: L
authors.lastname: Raz
authors.affiliation: a Department of Physiology and Biomedical Engineering , Mayo Clinic , Rochester , Minnesota , USA ;
authors.forename: L V
authors.initials: LV
authors.lastname: Hunter
authors.affiliation: b Department of Biostatistics and Medical Informatics , University of Wisconsin , Madison , WI , USA ;|c Department of Medicine , University of Wisconsin and Geriatric Research, Education and Clinical Center, Madison VA Hospital , Madison , WI , USA ;
authors.forename: N M
authors.initials: NM
authors.lastname: Dowling
authors.affiliation: d Department of Neurology , Emory University , Atlanta , GA , USA ;
authors.forename: W
authors.initials: W
authors.lastname: Wharton
authors.affiliation: c Department of Medicine , University of Wisconsin and Geriatric Research, Education and Clinical Center, Madison VA Hospital , Madison , WI , USA ;
authors.forename: C E
authors.initials: CE
authors.lastname: Gleason
authors.affiliation: a Department of Physiology and Biomedical Engineering , Mayo Clinic , Rochester , Minnesota , USA ;
authors.forename: M
authors.initials: M
authors.lastname: Jayachandran
authors.affiliation: a Department of Physiology and Biomedical Engineering , Mayo Clinic , Rochester , Minnesota , USA ;
authors.forename: L
authors.initials: L
authors.lastname: Anderson
authors.affiliation: c Department of Medicine , University of Wisconsin and Geriatric Research, Education and Clinical Center, Madison VA Hospital , Madison , WI , USA ;
authors.forename: S
authors.initials: S
authors.lastname: Asthana
authors.affiliation: a Department of Physiology and Biomedical Engineering , Mayo Clinic , Rochester , Minnesota , USA ;|e Department of Surgery , Mayo Clinic , Rochester , Minnesota , USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D000279:Administration, Cutaneous; D000339:Affect / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D012701:Serotonin / Q000097:blood*
chemical_list: D004966:Estrogens, Conjugated (USP); D012701:Serotonin; D004958:Estradiol
keywords: 17β-estradiol; 5-hydroxytryptamine; Conjugated equine estrogen; Kronos Early Estrogen Prevention Study; platelet