Short-term and prolonged treatment with oral contraceptives and liver function

Experiments on female rats were performed to observe the effects of progesterone and two synthetic progestens: ethinodiol-diacetate and methylestrenolone on liver function. In acute experiments animals were treated for the duration of one sexual cycle. All three compounds prolonged the hexobarbital biotransformation time. This effect is reversible and normalised 48 h after stopping treatment. The testosterone inducement of microsomal mixed function oxydases remained at the level of controls after methylestrenolone pretreatments and was even higher in the ethinodiol-diacetate and progesterone pretreated animals. Subacute and chronical treatments lasting for two or more sexual cycles resulted in the same slight inhibition of hexobarbital biotransformation when performed with the two progestogens. Chronical progesterone administration prolonged significantly hexobarbital biotransformation time. This impairement is also reversible. Our results pertain to a moderate, transitive inhibition of hexobarbital metabolism during short-term and prolonged progesterone and progestogen treatment. This effect may be easily suspended by interrupting drug administration or inducing microsomal enzymes with a single dosage of testosterone. In our progesterone experiments the inhibition of liver function increased with dosage and exposition time. In case of the two examined progestogens exposition time has not been proven as a predisposing factor for impairing liver function.