Abstract
OBJECTIVE: To characterize the influence of early life stress on peripheral basal inflammatory markers across the menopause transition. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.