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.

Plasma Homoarginine Concentrations According to Use of Hormonal Contraception.

Estrogen is a potent vasodilator through activation of endothelial nitric oxide synthase (eNOS). Arginine and its homologue homoarginine are substrates for NOS, while asymmetric dimethylarginine (ADMA) is a NOS inhibitor. Healthy, never-pregnant women aged 18 to 40 years (n = 158) were categorized according to use of hormonal contraception into non-users (n = 76), users of estrogen contraceptives (EC-users, n = 58) and users of progestins-only contraceptives (PC-users, n = 24). Plasma homoarginine, arginine, ADMA and SDMA concentrations were assayed using a LC-MS/MS method. Compared to non-users, EC users had higher plasma homoarginine (median (interquartile range) 1.63 (1.24, 2.04) vs. 2.39 (2.05, 2.85) µmol/L, p < 0.001), lower arginine (80.8 (72.4, 94.3) vs. 72.1 (62.9, 85.1) µmol/L, p = 0.008) and ADMA (0.52 (0.46, 0.59) vs. 0.48 (0.42, 0.54) µmol/L, p = 0.003) concentrations. The lowest median plasma homoarginine concentration (1.34 (0.92, 1.75) µmol) was seen in PC-users. No differences were seen in SDMA concentrations according to use of hormonal contraception. In healthy, never-pregnant women aged 18 to 40 years, use of estrogen containing contraception was associated with significantly higher plasma concentrations of homoarginine and lower plasma concentrations of arginine and ADMA as compared to non-users, while the lowest plasma homoarginine concentrations were seen in progestin-only users. Whether the observed changes in relation to use of hormonal contraception have an impact on cardiovascular status, should be evaluated in an intervention study.

Predictors of mercury, lead, cadmium and antimony status in Norwegian never-pregnant women of fertile age.

BACKGROUND: The toxic trace elements mercury (Hg), lead (Pb), cadmium (Cd) and antimony (Sb) are transferred over the placenta to the fetus and secreted into the breastmilk. All four elements bioaccumulate in the body and as maternal age at delivery is increasing in industrialized countries, the burden of toxic trace elements in never-pregnant women of fertile age is of concern. METHODS: Healthy, never-pregnant women aged 18 to 40 years (n = 158) were recruited between June 2012 and March 2015 in Bergen, Norway. Clinical data were collected and non-fasting venous blood samples were analyzed for whole blood Hg, Pb and Cd and serum Sb by ICP-MS and related to diet and life style factors. RESULTS: In a multiple linear regression model, increasing age was associated with higher levels of Hg and Sb, but diet and life style factors were more important predictors. Median whole blood Hg was increased by a factor of 70 in women who had fish for dinner ≥1/week, compared to women who rarely or never ate fish (p<0.001). Alcohol intake was the strongest predictor for whole blood Pb, while use of tobacco was the strongest predictor for whole blood Cd. Being a vegetarian was associated with lower levels of both Hg and Sb. CONCLUSIONS: As toxic trace elements tend to bioaccumulate in the body, increasing maternal age at delivery may represent a threat to the next generation. In a group of healthy Norwegian never-pregnant women, age contributed to Hg and Sb levels, but diet and life style factors were stronger determinants of whole blood Hg, Pb, Cd and serum Sb levels. Continuous public actions are needed to reduce modifiable and preventable sources of potentially deleterious toxins to minimize the exposure in children and fertile women.