Key result
Transdermal 17β-estradiol and oral conjugated equine estrogens increased mean platelet serotonin by 107.0% and 84.5%, respectively, compared to 39.8% with placebo.
Why the study?
Does oral conjugated equine estrogens or transdermal 17β-estradiol affect platelet serotonin, vascular function, and mood in women?
RCT (n=79)
Does oral conjugated equine estrogens or transdermal 17β-estradiol affect platelet serotonin, vascular function, and mood in women?
Oral conjugated equine estrogens may improve mood and endothelial function through mechanisms involving platelet serotonin uptake and release.
Answers are grounded in this paper and cite their sources.
May mediate mood benefits via platelet serotonin; extends mechanistic RCT evidence for menopausal hormone therapy.
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.
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Raz et al. (2015) reported an RCT. Oral conjugated equine estrogens (oCEE) or transdermal 17β-estradiol (tE2) vs. Placebo was evaluated on Mean platelet content of 5-HT. Transdermal 17β-estradiol and oral conjugated equine estrogens increased mean platelet serotonin by 107.0% and 84.5%, respectively, compared to 39.8% with placebo.
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