Schilder C M T, Schagen S B
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Minerva Ginecol. 2007 Aug;59(4):387-401.
(Pre)clinical research suggests that estrogens play a role in brain- and cognitive functioning. It is, among others, hypothesized that estrogens have a beneficial effect on neurotransmitters that are involved in cognitive processes, protect the brain by exerting anti-inflammatory actions after ischemic injury, promote survival of brain cells, and increase cerebral blood flow and glucose transport into the brain. Neuropsychological studies suggest that natural changes in estrogen levels are associated with (small) changes in cognitive functioning, for example during the menstrual cycle. In estrogen substitution studies, however, contradicting results are found, suggesting that substitution can have both beneficial and detrimental effects on cognitive functioning. Hormonal therapy for breast carcinoma lowers estrogen levels or blocks the growth-promoting effects of estrogens. The neuropsychological studies conducted so far give, though they vary highly in design, measures and participants, some indications for effects on cognition: ovariectomy, treatment with LHRH analogues, anastrozole and tamoxifen seem to be associated with (small) negative effects on some tests. It is unclear whether those effects are reversible, and whether time on therapy is associated with the seriousness of the effects. Raloxifene, currently under study for breast cancer prevention, does not seem to have detrimental effects on cognitive functioning. For the aromatase inhibitors letrozole and exemestane no data are available yet. Because the role of hormonal therapy in breast cancer treatment is increasing, the medical grounds for prescribing are expanding and physicians can make a choice from a broad spectrum of hormonal treatments, potential effects on cognitive functioning should be part of long-term drug safety evaluations.
（临床前）研究表明，雌激素在大脑和认知功能中发挥作用。其中，有人推测雌激素对参与认知过程的神经递质具有有益作用，在缺血性损伤后通过发挥抗炎作用保护大脑，促进脑细胞存活，并增加脑血流量和葡萄糖向大脑的转运。神经心理学研究表明，雌激素水平的自然变化与认知功能的（微小）变化有关，例如在月经周期期间。然而，在雌激素替代研究中发现了相互矛盾的结果，表明替代对认知功能可能既有有益影响也有有害影响。乳腺癌的激素疗法可降低雌激素水平或阻断雌激素的促生长作用。迄今为止进行的神经心理学研究，尽管在设计、测量方法和参与者方面差异很大，但给出了一些关于对认知影响的迹象：卵巢切除术、使用促性腺激素释放激素类似物、阿那曲唑和他莫昔芬治疗似乎与某些测试中的（微小）负面影响有关。尚不清楚这些影响是否可逆，以及治疗时间是否与影响的严重程度相关。目前正在研究用于预防乳腺癌的雷洛昔芬似乎对认知功能没有有害影响。对于芳香酶抑制剂来曲唑和依西美坦，目前尚无相关数据。由于激素疗法在乳腺癌治疗中的作用不断增加，开药的医学依据不断扩大，医生可以从广泛的激素治疗方法中进行选择，因此对认知功能的潜在影响应成为长期药物安全性评估的一部分。
