Systemic Lupus Erythematosus (SLE) is a disease in which genetically determined immune abnormalities are potentially triggered by hormonal factors and other environmental stimuli. The female gender predilection of this disease during the childbearing years (F:M, 12:1) infers that sex hormones may play a role in the pathogenesis. Despite conflicting data on the effects of exogenous estrogens and progestins on disease activity in SLE, oral contraceptives and estrogen replacement therapy are generally avoided despite the clear benefit of these preparations in providing effective birth control and in preventing cardiovascular disease and osteoporosis, both which occur prematurely in these patients. In order to clarify the effects of exogenous sex hormones in SLE, we must better understand the relationship between endogenous sex hormones and disease activity. Up to 60% of SLE women report adverse symptoms suggestive of disease activity during certain times of the menstrual cycle. Whether these symptoms represent a true exacerbation of SLE is unclear. If disease activity does parallel menstrual cycling, it is unknown whether this represents a response to normal or abnormal hormonal fluctuations. If hormonal profile are similar in SLE women and age-similar controls, this suggests that SLE women may have an abnormal response to normal levels of sex hormones. One could postulate that this is a hormone receptor or post-receptor phenomenon, or that there are abnormalities in estrogen metabolism. Elevated levels of 16 alpha- hydroxyestrone and estriol (more potent feminizing metabolites) and low levels of the 2 alpha-hydoxylated estrogens have been reported in these patients. Whether these metabolites are associated with disease activity in SLE is unknown. Based on the alterations in estrogen metabolism reported in women with SLE, we will examine the plausible candidate genes in which genetic variation may contribute to SLE phenotype. Our study will determine whether women with SLE have significantly different sex hormone profiles (estradiol/progesterone) during the menstrual cycle than non-SLE women and whether a relationships exists between a given hormonal milieu and disease activity.
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