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

• Type of Material: Article
• Authors: Limor Raz Limor Raz, Mayo Clinic; Larry Hunter, Mayo Clinic; N. Maritza Dowling, University of Wisconsin; Whitney Wharton, Emory University; Carey Gleason, University of Wisconsin; Muthuvel Jayachandran, Mayo Clinic; Layne Anderson, Mayo Clinic; Sanjay Asthana, University of Wisconsin; Virginia Miller, Mayo Clinic
• Language: English
• Date: 2016-01-02
• Publisher: Taylor
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 International Menopause Society
• Final Published Version (URL): http://dx.doi.org/10.3109/13697137.2015.1116504
• Title of Journal or Parent Work: Climacteric
• ISSN: 1369-7137
• Volume: 19
• Issue: 1
• Start Page: 49
• End Page: 59
• Grant/Funding Information: Study medications for KEEPS were supplied in part by Bayer Health Care and by Abbott Pharmaceuticals.; The Aurora Foundation to the Kronos Longevity Research Institute, NIH HL90639, NS066147, HD65987, AG029624, P50 AG033514, UL1 RR0241501 and the Mayo Foundation.
• Keywords: POSTMENOPAUSAL WOMEN; 5-hydroxytryptamine; EARLY ESTROGEN PREVENTION; DEPRESSIVE SYMPTOMS; BINDING SITES; MESSENGER-RNA LEVELS; RISK-FACTORS; MENOPAUSAL WOMEN; CONSENSUS STATEMENT; PLATELET REACTIVITY; 17-estradiol; Science & Technology; platelet; Conjugated equine estrogen; Kronos Early Estrogen Prevention Study; Life Sciences & Biomedicine; Obstetrics & Gynecology; ENDOTHELIAL FUNCTION
• Research Categories: Biology, Biostatistics; Engineering, Biomedical; Health Sciences, Medicine and Surgery

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.