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 years and older from the National Health and Nutrition Examination Survey (NHANES; 1999-2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence ORs (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 years and older, ANA prevalence was associated with parity (P < 0.001; parous vs. 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 vs. 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.

Figure 1. Prevalence of ANA by age depends on parity

Weighted ANA prevalence estimates and 95% confidence intervals

Figure 2. Parity explains age-associated increase in ANA prevalence in women ages 12–59, but not in those ages 60+

Prevalence Odds Ratios (POR) were estimated by survey logistic regression for increasing decade of age; the trend test for age by ANA is shown. ¹Estimates shown in the upper panel are adjusted for race/ethnicity and poverty-index-ratio ²Estimates shown in the lower panel are also adjusted for parity in women ages 12–59 and parity plus age at menarche in women ages 60 and older.