A decrease in serum liver enzyme levels in patients with primary biliary cirrhosis during treatment with ethinyl estradiol [1] led to a study of this drug in six women with chronic inflammatory liver disease. Patient ages ranged from 28 to 72 years (mean, 60 years). All aspartate aminotransferase and other serum enzyme levels were greater than twice the normal level for more than 6 months. Examination of liver biopsy specimens showed inflammation, piecemeal necrosis, or fibrosis. One patient was positive for the antibody to hepatitis C virus, 1 had autoimmune chronic active hepatitis, 1 was positive for hepatitis B surface antigen and hepatitis e antigen, and 3 had cryptogenic hepatitis. Patients were studied for 6 months to 7 years.

After pretreatment control periods (>3 months), 0.02 mg of ethinyl estradiol was given using a 21-day on-treatment and 7-day off-treatment cycle, with intermittent control periods during the off-treatment cycle. In all patients, enzyme levels after treatment were significantly lower than levels before treatment: Alkaline phosphatase decreased from 459 IU/L to 236 IU/L; glutamyl transferase, from 162 IU/L to 50 IU/L; and aspartate aminotransferase, from 103 IU/L to 61 IU/L (P = 0.05; Wilcoxon signed-rank test). The response was characterized by an initial decrease in enzyme levels, usually within 4 weeks; return to elevated levels when the drug was withheld; improvement on re-treatment; and enhancement of the enzyme-lowering effect with prolonged treatment.

The patient with autoimmune chronic active hepatitis responded in two treatment periods; liver biopsy indicated that inflammation almost completely resolved. All patients showed similar decreases in enzyme levels while receiving ethyl estradiol. In three patients, therapy was subsequently discontinued because of gallstones, withdrawal bleeding, or alcohol abuse, respectively.

Alteration of an autoimmune process by ethyl estradiol may be proposed as the mechanism of these effects. A similar theory has been proposed by McFarlane [2] and Lunel [3].