Environmental Epidemiology and Risk Factors for Autoimmune Disease

M. A. Dooley, MD, MPH, S. L. Hogan, PhD, MPH


Curr Opin Rheumatol. 2003;15(2) 

In This Article

Hormonal Exposures

A number of hormonal and reproductive factors were found not to be associated with the onset of SLE in the CLU study. The unassociated factors include early menarche, early natural menopause, number of pregnancies or live births, and current use or duration of use of hormone replacement therapy or oral contraceptives.[19*] Hormonal variability has been evaluated in the setting of established SLE in both mice and humans as risk factors for disease severity and progression. No prior human studies have evaluated these specific factors in terms of the risk of onset of SLE. Studies evaluating a posible association between the use of oral contraceptives and the onset of SLE[42,43,44] were negative; one study reported only a weak association.[43] A variety of hormonal factors have been associated with severity and progression of SLE but few associations have been observed with the onset of SLE.[19*] However, a strong association has been noted in observational studies between the use of hormone replacement therapy and the onset of SLE,[45,46,47] not observed in the CLU study.[19*]

The lack of expected hormonal associations observed in the CLU study should be confirmed by exploration of other study samples. Differences in control of potential confounding measures, age at menopause, and in the types of replacement therapies available for evaluation may account for the inconsistency in results. Furthermore, the CLU study had limited sample size in specific subgroups by type of hormone replacement therapy, duration of its use, and among former users. A large sample that focuses on post-menopausal women and collects detailed and validated use of hormone replacement therapies will be needed. Such a study of women with established SLE (SELENA study) has recently completed enrollment.[47]

The strongest hormonal-related associations seen in the CLU study were that a history of breast-feeding was associated with a decreased risk of developing SLE, while a history of pre-eclampsia was associated with an increased risk of developing SLE.[19*] These provocative results have not been previously observed in SLE, but have been reported in RA.[48]


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