Sulfobromophthalein clearance tests before and after ethinyl estradiol administration, in women and men with familial history of intrahepatic cholestasis of pregnancy.

To test the hypothesis that intrahepatic cholestasis of pregnancy represent an abnormal reaction to estrogens in genetically predisposed individuals, the sulfobromophthalein disappearance curve from blood was compared before and after ethinyl estradiol administration (0.1 mg/day, during 6 days) in multiparous women with or without a past history of intrahepatic cholestasis of pregnancy, and in nulliparous women and men with or without a familial history of the disease. BSP concentration in blood, from 5 to 65 min after a single i.v. injection of the dye (5 mg/kg body wt), was fitted into biexponential curves using a computerized program. Ethinyl estradiol administration decreased the slope of the second component of the curve (k2) in most subjects and in both sexes. This effect was greater in multiparous women with a past history of intrahepatic cholestasis of pregnancy than in their controls. An exaggerated response to ethinyl estradiol was more frequently found in nulliparous women, and in men, with a familial history of the disease than in those without it. These observations suggest the presence of a constitutional abnormality in the metabolic interactions between estrogens and the liver, independent from pregnancy itself. This abnormality could be genetically transmitted by individuals from either sex, determining a predisposition to develop intrahepatic cholestasis of pregnancy in their female descendants.