Changes in Menopause Stage, Body Mass, and Fat Mass as Drivers of Midlife Changes in C-reactive Protein Levels: A Prospective Cohort Study

Abstract Background. Serum levels of C-reactive protein (CRP), a marker of chronic inflammation, increase in many, but not all, women going through the menopause transition (MT). It is not known whether this is driven entirely by changes in body mass and fat mass in midlife or by other physiological changes during the MT. Methods. We use individual fixed effects analysis of repeated measurements across the MT, in a multi-ethnic cohort of 1681 women followed for over two decades (1996–2018), to address this knowledge gap; we also test whether associations between body mass increase (likewise fat mass increase) and CRP increase differ by race/ethnicity. Results. Adjusted for changes in body mass index (BMI), change in menopause stage was not associated with change in CRP. Every kg/m 2 within-woman increase in BMI was associated with 16% increase in serum CRP (p<.0001). Similarly, every kg/m 2 within-woman increase in fat mass index (total fat mass divided by square of height, FMI) was associated with 23% increase in serum CRP (p<.0001). The association of BMI increase with CRP increase was smaller in Black than in White women: 12% vs. 18% per kg/m 2 (p = 0.03 for test of difference), but not statistically different in Chinese and Japanese women relative to White women. On the other hand, race/ethnicity did not modify the association of FMI increase with CRP increase, but the association was modestly smaller in natural and surgical postmenopause than in premenopause: 20% and 15% vs. 22% per kg/m 2 , respectively (p = 0.001 and 0.05 for tests of difference). Conclusions. Midlife increases in CRP levels in women are not directly related to menopause stage but appear to be driven by increases in body mass, particularly fat mass. While changes in body mass have different implications for CRP changes in Black vs. White women, increases in fat mass have similar associations with CRP increases in Black and White women. However, changes in fat mass have modestly smaller associations with CRP changes in postmenopause than before the MT.