Steroid-type cholestasis is a pure reaction with little or no hepatocellular inflammation. Gradual onset of cholestasis without systemic symptoms is usual. Alkaline phosphatase is elevated, but aminotransferase levels are usually unimpressive, and liver biopsy shows only centrizonal bile stasis with little portal reaction or hepatocellular disarray. Complete resolution follows drug withdrawal. This type of cholestasis is produced by oral contraceptives, methyltestosterone, and related drugs, most of which are C-17 alkylated steroids. About 1 to 2% of women taking oral contraceptives develop the syndrome; worldwide figures vary, possibly because of genetic factors. The reaction appears to be an exaggeration of the physiologic effect of sex hormones on bile formation, rather than an immunologic sensitivity or membrane cytotoxicity. Interference with canalicular water flow, microfilament dysfunction, and altered membrane fluidity may be responsible, but the exact mechanism of cholestasis is uncertain.
Steroid-related cholestasis is closely related to
cholestasis of pregnancy (see
Hepatic Disorders in Ch. 251). Women with cholestasis of pregnancy may subsequently develop cholestasis with oral contraceptive use; likewise, women who develop cholestasis while taking oral contraceptives may subsequently develop cholestasis of pregnancy.