LAUSR

Reproductive events, such as ovulation, trigger an inflammatory cascade. Few studies have examined their long-term influence on inflammatory profiles. We included 3,393 premenopausal and 3,915 postmenopausal women with intact ovaries/uterus from the Nurses' Health Studies, and estimated lifetime ovulatory years (LOY) as age at menopause (age at blood collection for premenopausal women) minus age at menarche, years of oral contraceptive (OC) use, and one year per pregnancy. After adjusting for other inflammation-related factors (e.g., BMI, exercise, diet, etc.), every 5-year increase in LOY was associated with lower C-reactive protein (CRP) in premenopausal (-11.5%; 95% CI: -15.0, -8.0; p<0.0001) and postmenopausal women (-7.2%; 95% CI: -10.0, -4.3; p<0.0001). Older age at menopause (p=0.007), earlier menarche (p=0.007), and shorter duration of OC use (p=0.002) were associated with lower CRP levels in postmenopausal women, whereas only OC duration was positively associated in premenopausal women (p<0.0001). LOY was modestly inversely associated with interleukin-6 only in postmenopausal women (p=0.04). Notably, the associations of CRP with LOY were similar in magnitude compared to those with exercise and a healthy diet, although weaker than that with BMI. Although many reproductive events induce acute inflammation, increased LOY was associated with lower chronic systemic inflammation even after menopause.