Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS.
Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS.
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DOI：
10.3109/13697137.2015.1116504
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Miller VM
中科院分区：
文献类型：
--
作者：
Raz L;Hunter LV;Dowling NM;Wharton W;Gleason CE;Jayachandran M;Anderson L;Asthana S;Miller VM
血清素（5-羟色胺，5-HT）受性类固醇激素调节，影响血管功能和情绪。在 Kronos 早期雌激素预防认知和情感辅助研究 (KEEPS-Cog) 中，随机接受口服结合马雌激素 (oCEE) 的女性比随机接受透皮 17β-雌二醇 (tE2) 或安慰剂 (PL) 的女性在情感情绪状态方面表现出更大的益处。这项研究检查了这些治疗对血小板 5-HT 含量的影响，作为大脑中 5-HT 合成和摄取的替代指标。对参加 KEEPS-Cog 的女性子集 (n = 79) 进行了以下测量：通过 ELISA 测量 5-HT，通过超声测量颈动脉内膜中层厚度 (CIMT)，通过反应性充血指数 (RHI) 测量内皮功能，以及通过情绪状态概况 (POMS) 问卷自我报告的情感情绪状态症状。 tE2、oCEE 和 PL 组中 5-HT 平均血小板含量分别增加了 107.0%、84.5% 和 39.8%。 oCEE 组中血小板 5-HT 与雌酮呈正相关，tE2 组中血小板 5-HT 与 17β-雌二醇呈正相关。在 PL 和 oCEE 组中，血小板 5-HT 显示与 RHI 呈正相关，但与 CIMT 无关。仅在 oCEE 组中，抑郁-沮丧和愤怒-敌意情绪评分的降低与血小板 5-HT 升高相关（r = -0.5，p = 0.02）。与 tE2 相比，oCEE 对 RHI 和情绪的影响可能与涉及血小板以及神经元 5-HT 摄取和释放的机制有关，并反映了血小板和大脑中雌酮向生物可利用的 17β-雌二醇的转化。
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. 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 hyperemia index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire. 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 associated with elevations in platelet 5-HT only in the oCEE group (r = −0.5, p = 0.02). 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.