Metcalf Christina A, Johnson Rachel L, Freeman Ellen W, Sammel Mary D, Epperson C Neill
University of Colorado Anschutz Medical Campus, USA.
University of Pennsylvania School of Medicine, USA.
Brain Behav Immun Health. 2021 Jun 1;15:100280. doi: 10.1016/j.bbih.2021.100280. eCollection 2021 Aug.
To characterize the influence of early life stress on peripheral basal inflammatory markers across the menopause transition.
Participants from the longitudinal Penn Ovarian Aging study were assessed for childhood adversity at study end (14 years) using the Adverse Childhood Experiences (ACE) questionnaire. Responses were categorized as low (0-1) or high (≥2) ACE exposure. The stored blood sample catalogue was reviewed to exclude those samples collected during use of medications that could impact immune status or medications suggestive of infection or allergies. Remaining blood samples (n = 640) from 167 participants were assayed for interleukin-6 (IL-6), interleukin 1-beta (IL-1β), high sensitivity C-reactive protein (hsCRP), and tumor necrosis factor alpha (TNF-α). Menopause staging (premenopause, early transition, late transition, and postmenopause) was determined by questionnaire and menstrual diaries at yearly assessments. Generalized linear models for repeated measures were used to quantify the association between outcomes of interest (i.e., IL-6, IL-1β, hsCRP, and TNF-α) and exposures (i.e., menopause stage, ACE status, their interaction) while controlling for relevant covariates (i.e., BMI, smoking, age at first blood sample, and race). Inflammatory marker levels were log-transformed for modeling.
Log IL-6 levels were higher in the late perimenopause versus premenopause (p = 0.035). Menopause stage × ACE interaction was observed for log IL-6, IL-1β, and TNF-α (p = 0.042, p = 0.054, p = 0.053, respectively); for individuals with high (≥2) ACE exposure, IL-6 was higher in the late perimenopause (p = 0.015) while IL-1β and TNF-α were lower in the postmenopause versus premenopause (p = 0.019 and p = 0.020).
Results from this investigation indicate that the late perimenopause stage may be a window of risk for inflammation, particularly for individuals with greater childhood adversity. Prospective studies designed to address childhood stress and inflammation across the menopause transition are needed to confirm these findings. Heightened inflammation, even if transitory, may have negative impact on healthy aging.
描述生命早期应激对绝经过渡期间外周基础炎症标志物的影响。
来自宾夕法尼亚卵巢衰老纵向研究的参与者在研究结束时（14岁）使用儿童期不良经历（ACE）问卷评估童年逆境情况。回答被分类为低（0 - 1）或高（≥2）ACE暴露。审查储存的血样目录，以排除在使用可能影响免疫状态的药物期间或提示感染或过敏的药物期间采集的样本。对167名参与者的剩余血样（n = 640）进行白细胞介素-6（IL-6）、白细胞介素1-β（IL-1β）、高敏C反应蛋白（hsCRP）和肿瘤坏死因子α（TNF-α）检测。通过问卷和每年评估时的月经日记确定绝经分期（绝经前、早期过渡、晚期过渡和绝经后）。使用重复测量的广义线性模型来量化感兴趣的结果（即IL-6、IL-1β、hsCRP和TNF-α）与暴露因素（即绝经阶段、ACE状态及其相互作用）之间的关联，同时控制相关协变量（即体重指数、吸烟、首次采血时的年龄和种族）。炎症标志物水平进行对数转换以进行建模。
围绝经期晚期的对数IL-6水平高于绝经前（p = 0.035）。在对数IL-6、IL-1β和TNF-α方面观察到绝经阶段×ACE相互作用（分别为p = 0.042、p = 0.054、p = 0.053）；对于ACE暴露高（≥2）的个体，围绝经期晚期IL-6更高（p = 0.015），而绝经后IL-1β和TNF-α低于绝经前（p = 0.019和p = 0.020）。
本研究结果表明，围绝经期晚期可能是炎症风险的一个窗口，特别是对于童年逆境较大的个体。需要设计前瞻性研究来探讨童年应激与绝经过渡期间炎症的关系以证实这些发现。炎症加剧，即使是短暂的，也可能对健康衰老产生负面影响。
