Autoimmune diseases are said to have high female/male (F/M) ratios, but these ratios are imprecise. Published definitions and classifications of autoimmune diseases differ substantially, as do the F/M ratios themselves. Imputed causality of autoimmune diseases requires better precision. Some thyroid, rheumatic and hepatic diseases consistently have high F/M ratios, but marked differences exist in the reported quantity of the ratios. Other autoimmune diseases have low F/M ratios. Because F/M ratios reflect incidence and not severity of disease, gonadal hormones, if they play a role, must do so through a threshold or permissive mechanism. Sex differences related to environmental exposure, X-inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences remain as alternate, theoretical, explanations for sex differences of incidence. The epidemiology of the sex-discrepant autoimmune diseases--young, female--suggests that an explanation for sex discrepancy lies in differential exposure, vulnerable periods, or thresholds, rather than in quantitative aspects of immunomodulation.
