Haase Gino, Liu Jason, Jordan Timothy, Rapkin Andrea, London Edythe D, Petersen Nicole
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Hum Brain Mapp. 2025 Aug 1;46(11):e70318. doi: 10.1002/hbm.70318.
Neuroimaging studies have reported that oral contraceptive pills (OCPs) alter brain connectivity, but findings have varied widely and are often derived from observational designs. Here, we used a randomized, double-blind, placebo-controlled crossover design to test for conceptual replication of three prior studies and to explore broader network-level effects of OCPs. Replication analyses largely did not confirm previously reported seed-based connectivity changes in edges containing amygdala, putamen, or dorsal anterior cingulate nodes (ps > 0.05). In the absence of a clear replication, we pursued exploratory analyses using functional connectome fingerprinting, a multivariate, data-driven method that allows parsimonious interrogation of connectivity changes simultaneously across the whole by detecting whole-brain connectivity patterns that distinguish individuals from one another. This approach revealed network-level changes during OCP use, especially within subcortical, executive, and somatomotor circuits. OCPs also increased between-subject similarity in functional connectomes (I, p < 0.001), suggesting a loss of individual idiosyncrasy while using OCPs. Intraclass correlations indicated that idiosyncrasy was significantly lowered in the default mode, executive, limbic, salience, somatomotor, and subcortical networks (all p < 0.05). Finally, changes in functional connectivity were significantly associated with increases in negative affect, with 13 connectivity edges showing significant (p < 0.001) correlations with DRSP symptom scores. These findings suggest that OCPs induce widespread and individually meaningful alterations to brain network organization, which may underlie mood-related side effects and should be considered in future neuroimaging research involving hormonal contraceptive users.
神经影像学研究报告称，口服避孕药（OCPs）会改变大脑的连通性，但研究结果差异很大，且往往来自观察性设计。在此，我们采用随机、双盲、安慰剂对照的交叉设计，对之前的三项研究进行概念性重复验证，并探索OCPs更广泛的网络层面效应。重复分析在很大程度上并未证实先前报道的在包含杏仁核、壳核或背侧前扣带回节点的边缘基于种子点的连通性变化（p>0.05）。在缺乏明确重复验证的情况下，我们采用功能连接组指纹识别法进行探索性分析，这是一种多变量、数据驱动的方法，通过检测区分个体的全脑连通性模式，能够简洁地同时探究整个大脑的连通性变化。这种方法揭示了使用OCPs期间的网络层面变化，尤其是在皮质下、执行和躯体运动回路中。OCPs还增加了功能连接组之间的个体间相似性（I，p<0.001），表明使用OCPs时个体特质有所丧失。组内相关性表明，在默认模式、执行、边缘、突显、躯体运动和皮质下网络中，特质显著降低（所有p<0.05）。最后，功能连通性的变化与负面影响的增加显著相关，有13条连通性边缘与DRSP症状评分显示出显著（p<0.001）相关性。这些发现表明，OCPs会引起大脑网络组织广泛且具有个体意义的改变，这可能是与情绪相关的副作用的基础，在未来涉及激素避孕使用者的神经影像学研究中应予以考虑。
