Genazzani A R, Spinetti A, Gallo R, Bernardi F
Department of Obstetrics and Gynecology, University of Pisa, Italy.
Maturitas. 1999 Jan 4;31(2):103-10. doi: 10.1016/s0378-5122(98)00112-1.
The central nervous system is an important target for sex steroid hormones. During the climateric period the rapid decline of gonadal steroids causes neuroendocrine changes in different areas of the brain. The failure of gonadal hormone production brings specific symptoms due to the central nervous system derangement. At the hypotalamic level estrogen withdrawal gives rise to vasomotor symptoms, eating behavior disorders and altered blood pressure control. Psychological disturbances such as depression, anxiety, irritability and mood fluctuation are related to estrogen-induced changes in the lymbic system. The hypothesis of specific neuroanatomical and neurophysiological effects of estrogen on the brain may also explain the correlation between estrogen deficiency and cognitive disturbances such as Alzheimer's type dementia (AD). The increasing interest in the influence of sex steroids on brain function has focused attention on hormonal replacement therapy. Clinical and epidemiological studies have demonstrated that estrogen therapy exerts a positive effect on vasomotor instability and improves psychological disturbances. The positive effects of estrogen on mood are probably related to its stimulatory action on adrenergic and serotoninergic tone. Estrogen may influence the cognitive function through different biological actions. Estrogen administration increases total cerebral and cerebellar blood flow, cerebral glucose administration and improves cholinergic tone, a key neurotransmitter in learning and memory. The evidence suggests that hormone replacement therapy may reduce the relative risk of developing AD. Progestagens and androgen may also have a role in the control of mood disorders. At present, few data are available regarding the influence that selective estrogen receptor modulators, a new class of compounds, can exert on the brain.
中枢神经系统是性类固醇激素的重要作用靶点。在更年期,性腺类固醇激素的迅速下降会导致大脑不同区域的神经内分泌变化。性腺激素分泌功能的衰退会因中枢神经系统紊乱而引发特定症状。在丘脑水平,雌激素撤退会引发血管舒缩症状、饮食行为紊乱以及血压控制改变。诸如抑郁、焦虑、易怒和情绪波动等心理障碍与雌激素引起的边缘系统变化有关。雌激素对大脑具有特定神经解剖学和神经生理学效应的假说,或许也能解释雌激素缺乏与认知障碍(如阿尔茨海默病型痴呆,即AD)之间的关联。对性类固醇激素对脑功能影响的兴趣日益浓厚,使得人们将注意力集中在了激素替代疗法上。临床和流行病学研究表明,雌激素疗法对血管舒缩不稳定具有积极作用,并能改善心理障碍。雌激素对情绪的积极作用可能与其对肾上腺素能和5-羟色胺能张力的刺激作用有关。雌激素可能通过不同的生物学作用影响认知功能。给予雌激素可增加大脑和小脑的总血流量、大脑葡萄糖摄取,并改善胆碱能张力,而胆碱能张力是学习和记忆中的关键神经递质。有证据表明,激素替代疗法可能会降低患AD的相对风险。孕激素和雄激素在控制情绪障碍方面或许也有作用。目前,关于一类新型化合物——选择性雌激素受体调节剂对大脑的影响,可用数据较少。