Influences of the menopause transition and adverse childhood experiences on peripheral basal inflammatory markers.
Level 3 - non-randomized controlled study
Non-randomized longitudinal cohort study with repeated measures.
PubMed 34589780 · doi:10.1016/j.bbih.2021.100280
What was done
This study evaluated the relationship between adverse childhood experiences (ACEs) and peripheral inflammatory markers across the menopause transition in 167 women from the longitudinal Penn Ovarian Aging Study (14-year follow-up). Childhood adversity was retrospectively assessed at study completion using the ACE questionnaire and classified as low (0–1) or high (≥2). A total of 640 stored blood samples (screened to exclude immunomodulating medications, acute infections, or allergies) 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). Generalized linear models for repeated measures evaluated the effects of menopause stage, ACE exposure, and their interaction on log-transformed inflammatory markers, adjusting for body mass index, smoking, age at initial sample, and race.
What was found
Log IL-6 levels were significantly higher in late perimenopause compared with premenopause (p = 0.035). Significant or borderline menopause stage × ACE interactions occurred for log IL-6 (p = 0.042), IL-1β (p = 0.054), and TNF-α (p = 0.053). Among women with high ACE exposure (≥2), IL-6 was elevated during late perimenopause compared with premenopause (p = 0.015), while IL-1β (p = 0.019) and TNF-α (p = 0.020) were lower in postmenopause compared with premenopause. hsCRP results were not reported with specific statistics in the abstract.
Why it matters
The findings suggest that the late perimenopausal transition represents a vulnerable period for heightened systemic inflammation (specifically IL-6), which may be pronounced in women who experienced early life adversity.
Limits
Childhood adversity was assessed retrospectively at the end of a 14-year study period, introducing potential recall bias. The sample size was modest (167 participants), absolute baseline/follow-up cytokine concentrations and confidence intervals were not provided in the abstract, and several interaction p-values were borderline (p ~ 0.05).
Cited by
- context Women entering perimenopause experience a significant increase in systemic inflammatory markers including hs-CRP, IL-6, and TNF-alpha.