更年期激素治疗和神经精神疾病的风险:一种药物向的门德尔随机化研究
Louise S Schindler1,2, Dipender Gill3, Hannah Oppenheimer4,5
1Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
npj women's health
|March 3, 2026
概括
针对雌激素受体 (ERα和ERβ) 的更年期激素治疗 (MHT) 对阿尔茨海默病风险或大脑结构没有影响. 然而,ERβ扰动与抑郁症风险增加有关.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 内分泌学 在内分泌学.
背景情况:
- 关于更年期激素治疗 (MHT) 对神经和精神疾病的影响存在相互矛盾的证据.
- 通过与雌激素受体 (ERα和ERβ) 相互作用,MHT的功能.
研究的目的:
- 研究雌激素受体 (ERα和ERβ) 干扰与阿尔茨海默病 (AD) 的风险,大脑结构,抑郁和焦虑之间的因果关系.
- 使用药物标孟德尔随机化 (MR) 评估ERα和ERβ活性的遗传代理.
主要方法:
- 使用两个样本的门德尔随机化 (MR) 分析.
- 利用了大型全基因组关联研究 (GWAS).
- 用ESR1和ESR2基因中的遗传变异作为ERα和ERβ扰动的仪器变量.
主要成果:
- 基因代理的ERα和ERβ扰动没有对阿尔茨海默病风险产生影响.
- 在ERα或ERβ扰动和皮质灰质,海马体积或白质超强度之间没有发现显著的关联.
- 基因代理的ERβ扰动与抑郁症风险增加有显著的关联 (β = -0.66,p = 0.002),但与焦虑症无关.
结论:
- 该研究没有证据表明MHT会影响阿尔茨海默病风险或大脑结构.
- 雌激素受体β (ERβ) 的扰动与抑郁症的风险增加有关.
- 强调需要在MHT向雌激素受体时考虑精神病学因素.
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