Tryptophan Metabolism in Women Using Steroid Hormones for Ovulation Control

Abstract

This is an extension of work recently reported by Rose regarding young women using a combination of progesterone and estrogen for ovulation control. The 10 subjects studied had an abnormal xanthurenic acid excretion after a loading dose of tryptophan. After treatment with 2.5 mg norethynodrel and .1 mg mestranol (Enovid-E) from Days 5 to 24 of the the cycle, 24-hour urine specimens were collected before and after administration of 2 gm of L-tryptophan. They were then given 25 mg of pyridoxine hydrochloride 4 times a day during the 48 hours required to repeat the tryptophan loading test. Controls were 18 healthy women not taking drugs. Metabolites of trytophan determined were indican, anthranilic acid glucuronide, 0-aminohippuric acid, kynurenic acid, acetylkynurenine, kynurenine, 3-hydroxykynurenine, xanthurenic acid, and N-methyl-2-pyridone-5-carboxamide. Urine specimines were analyzed for these and for 4-pyridoxic acid taking usual precautions to avoid dietary factors or drugs which might vitiate the results. At first the ingestion of the steroid had no significant effect on the basal excretion of urinary tryptophan metabolites. However, after the loading dose of tryptophan, the subjects taking Enovid E- excreted a mean level of 697 micro-moles of xanthurenic acid compared with a mean level of 29.8 micro-moles in controls. Some of the other metabolites were also excreted in increased quantities: 3-hydroxykynurenine, kynurenine, kynurenic acid, and acetylkynurenine. The others were excreted in normal quantities. When experimental subjects were given 100 mg/day of supplemental pyridoxine hydrochloride, tryptophan metabolism was essentially normal. These results should be considered in human metabolic studies of pyridoxine-requiring enzyme systems.