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15 December 1995 | Volume 123 Issue 12 | Page 962
Despite anecdotal clinical and experimental evidence in various animal models of lupus, which support the belief that estrogens and systemic lupus erythematosus do not mix, the sex hormone hypothesis has not been proved in humans. We agree with Dr. Buyon and colleagues. Our study widens the scope of potential side effects of postmenopausal estrogens and underscores the dilemma of prescribing hormone replacement in normal women and the need to balance the risks and benefits. A distinction must be made between prescribing estrogens to healthy women and prescribing them to women with established lupus. Our study addresses the former and provides the most prospective data on the issue.
Buyon and colleagues mention two potential confounders, which in epidemiology are known as testing bias and bias by indication. Both are possible but are unlikely to be present in a sufficient magnitude to explain the observed risk ratios. That the women who developed systemic lupus erythematosus while receiving hormone replacement therapy did not do so when they were pregnant is interesting. We can only speculate why this occurred. Several sex steroids seen in pregnancy have estrogenic activity; they may not all be of etiologic importance or even important at all.
Dr. Piette and colleagues suggest that premature ovarian failure may have been a potential confounder. In our cohort, natural menopause before the age of 40 years is exceedingly rare and could not explain the association we observed.
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