激素替代疗法对KEEPS研究中血清素、血管功能及情绪的不同影响。
Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS.
作者信息
Raz L, Hunter L V, Dowling N M, Wharton W, Gleason C E, Jayachandran M, Anderson L, Asthana S, Miller V M
机构信息
a Department of Physiology and Biomedical Engineering , Mayo Clinic , Rochester , Minnesota , USA ;
b Department of Biostatistics and Medical Informatics , University of Wisconsin , Madison , WI , USA ;
出版信息
Climacteric. 2016;19(1):49-59. doi: 10.3109/13697137.2015.1116504. Epub 2015 Dec 10.
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.
背景
血清素（5-羟色胺，5-HT）受性类固醇激素调节，并影响血管功能和情绪。在克诺诺斯早期雌激素预防认知与情感辅助研究（KEEPS-Cog）中，随机接受口服结合马雌激素（oCEE）的女性在情感情绪状态方面比随机接受经皮17β-雌二醇（tE2）或安慰剂（PL）的女性获益更大。本研究将这些治疗对血小板5-HT含量的影响作为大脑中5-HT合成和摄取的替代指标进行了检测。
方法
在参与KEEPS-Cog的一部分女性（n = 79）中测量了以下指标：通过酶联免疫吸附测定法检测5-HT，通过超声检测颈动脉内膜中层厚度（CIMT），通过反应性充血指数（RHI）检测内皮功能，以及通过情绪状态量表（POMS）问卷自我报告情感情绪状态症状。
结果
tE2组、oCEE组和PL组的血小板5-HT平均含量分别增加了107.0%、84.5%和39.8%。oCEE组中血小板5-HT与雌酮呈正相关，tE2组中与17β-雌二醇呈正相关。在PL组和oCEE组中，血小板5-HT与RHI呈正相关，但与CIMT无关。仅在oCEE组中，抑郁-沮丧和愤怒-敌意情绪得分的降低与血小板5-HT的升高有关（r = -0.5，p = 0.02）。
结论
与tE2相比，oCEE对RHI和情绪的影响可能与涉及血小板以及可能神经元摄取和释放5-HT的机制有关，并反映了雌酮在血小板和大脑中转化为生物可利用的17β-雌二醇。
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