Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women

Abstract

Background Autoantibodies are of growing interest in cancer research as potential biomarkers; yet the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population, and are more prevalent in women and older adults. Here we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women. Methods We analyzed data on reproductive history and exogenous hormone use in relation to serum ANA in 2,037 females ages 12 and older from the National Health and Nutrition Examination Survey (NHANES; 1999–2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were adjusted for age, race and poverty-income-ratio, and models were stratified by menopause status. Results In premenopausal women ages 20 and older, ANA prevalence was associated with parity (p<0.001; parous versus nulliparous POR=2.0; 95%CI 1.2, 3.4), but in parous women ANA did not vary by number of births, age at first birth, years since last birth or breastfeeding. In postmenopausal women, ANA prevalence was associated with an older age at menarche (p=0.019; age 16–20 versus 10–12 years POR=3.0, 95%CI 1.6, 5.9), but not with parity. Oral contraceptives and estrogen therapy were not associated with a higher ANA prevalence. Conclusions Childbearing (having had one or more births) may explain age-associated elevations in ANA prevalence seen in premenopausal women. Impact These findings highlight the importance of considering reproductive history in studies of autoimmunity and cancer in women.

Association between Vitamin D Deficiency and Antinuclear Antibodies in Middle-Aged and Older U.S. Adults

“…In this sample restricted to middle age and older U.S. adults, ANA was not observed to increase with age in contrast to previous reports using NHANES data (14, 25). These prior analyses that showed ANA increasing with age included a broader age range covering the life course from 12-70+ years (14).…”

Recent Approaches To Optimize Laboratory Assessment of Antinuclear Antibodies

“…The ANA prevalence observed in the U.S. study was comparable to that observed in a recently published report from Germany (5). As in other previous reports, women had higher frequencies of ANA positivity than did men in both studies (5,6,37), which could be related to reproductive and hormonal factors (38). While increasing frequency of ANA positivity with increasing age and according to gender has been reported, there are likely other factors involved.…”

Associations Between Selected Xenobiotics and Antinuclear Antibodies in the National Health and Nutrition Examination Survey, 1999–2004

“…Among the most commonly measured biomarkers of autoimmunity are antinuclear antibodies (ANA), which are traditionally assessed by indirect immunofluorescence and are a heterogeneous group of autoantibodies targeting both nuclear and cytoplasmic components of cells ( Tan 1989 ). Although ANA are associated with a number of autoimmune diseases, they can also develop in apparently healthy individuals after infections or following the use of medications; furthermore, their prevalence tends to be higher in parous females and the elderly ( Hollingsworth et al 1996 ; Parks et al 2014 ; Satoh et al 2007 , 2012 ). Many persistent organic pollutants (POPs) exhibit hormone-disruption properties that could lead to increased ANA, and exposure to POPs has been hypothesized to increase the risk of systemic lupus erythematosus ( Cooper et al 1998 ).…”