Lower levels of the neuroprotective tryptophan metabolite, kynurenic acid, in users of estrogen contraceptives

Changes in kynurenine metabolites are reported in users of estrogen containing contraception. We have assessed kynurenines, vitamin B6, vitamin B2 and the inflammation markers, C-reactive protein (CRP) and neopterin, in healthy, never-pregnant women between 18 and 40 years (n = 123) and related this to their use of hormonal contraception. The population included 58 women, who did not use hormonal contraceptives (non-users), 51 users of estrogen-containing contraceptives (EC-users), and 14 users of progestin only contraceptives (PC-users). EC-users had significantly lower plasma kynurenic acid (KA) and higher xanthurenic acid (XA) levels compared to non-users. Serum CRP was significantly higher and negatively associated with both vitamin B6 and B2 status in EC-user compared to non-users. No significant differences in any parameters were seen between PC-users and non-users (p > 0.1). The low KA and high XA concentration in users of estrogen containing contraception resemble the biochemical profile observed in vitamin B6 deficiency. The hormonal effect may result from interference with the coenzyme function of vitamin B6 and B2 for particular enzymes in the kynurenine metabolism. KA has been suggested to be neuroprotective and the significantly reduced concentration in EC-users may be of importance in the observed increased risk of mood disorders among users of oral contraceptives.