Exogenous female hormones and rheumatoid arthritis: a methodological view of the contradictions in the literature.

The purpose of this review is not to resolve the contradictory findings that are present in the literature. Rather, it considers a selected number of issues that may pertain to some future understanding of the current controversy. Furthermore, certain issues such as biological plausibility and the absence of a definitive dose, duration, or timing relationships are not discussed. If the association of the use of exogenous female hormones with the prevention of rheumatoid arthritis came to be accepted as likely causal, basic scientists might well unravel the biological processes involved. The dose and duration of exposure to the hormones and the timing of the exposure (current use versus past use) in relation to the preventative effect remains unclear. While clearly a point against a causal relationship the possibility exists that this may result from errors in recall or that prior hormone exposure may 'vaccinate' a woman against the disease. A number of studies have been published only in abstract or are still underway. Reanalysis of existing data sets may also provide some insight into the contradictory findings. The issues raised in this review are of relevance to investigators. They may also be used by readers interested in this topic who wish to attempt to resolve the conflicts in the hormone-rheumatoid arthritis literature for themselves.