Effect of ovarian hormones and oral contraceptives on tryptophan metabolism

Abstract

Women taking oral contraceptives excrete in urine increased amounts of tryptophan metabolites of the nicotinic acid ribonucleotide pathway. After an oral tryptophan load of 5 gm 15 women on pills excreted several fold higher amounts of kynurenine 3-hydroxykynurenine xanthurenic acid and 3-hydroxyanthranilic acid the same metabolites usually increased in pyridoxine deficiency. When large doses of pyridoxine were given before tryptophan load these substances were excreted in normal amounts. The estrogen in the pill was responsible as shown by tests in 7 women and 1 man given ethinyl estradiol or stilbestrol. Even without tryptophan loading increased amounts of 3-hydroxyanthranilic acid could be detected by thin layer electrophoresis in urine from pill users; and nul-methylnicotinamide was also found raised in another group of Enovid users. 2 mechanisms are proposed for these increased metabolites. Liver enzymes particularly tryptophan oxygenase are known to be induced by mestranol-norethynodrel in rats possibly preempting all available pyridoxine a cofactor for several enzymes in the pathway. Alternatively ester sulfates could competitively bind the cofactor but this suggestion is controversial. Clinically abnormal tryptophan metabolism is significant because the product of another tryptophan pathway 5-hydroxytryptamine is low in depression. There is evidence that induction of rat liver tryptophan oxygenase is accompanied by decrease in brain 5-hydroxytryptamine.