Copper and Liver Function Indicators Vary Depending on the Female Hormonal Cycle and Serum Hormone Binding Globulin (SHBG) Concentration in Healthy Women

Abstract

Previous studies showed that responses to chronic administration of copper were significantly associated with gender, raising the need to better characterize the relation between the effects observed and stradiols. The objective of this study was to measure copper and liver function indicators and the sex hormone binding globulin (SHBG) serum concentrations in healthy adults exposed to copper, grouped by sex and phase of the female hormonal cycle. Healthy females on day 7 (follicular phase, Group 1, n = 39), on day 21 (secretory phase, Group 2, n = 34) and males (comparison group, Group 3, n = 34) received 8 mg Cu/day (as copper sulfate), orally, for 6 months. On days 0, 30, 60, 120, and 180, the serum concentration of copper, ceruloplasmin, liver aminotransferases, and SHBG were measured. Analysis of results included analysis of variance (ANOVA; repeated measures) and the post hoc Bonferroni correction. Participants remained healthy throughout the study period, including aminotransferases below the cut off in all measures. GGT, AST, and ALT activities were significantly different by group and by time (ANOVA repeated measures P < 0.05). Six-month curves of serum copper and ceruloplasmin concentrations were different by group, by time and interaction group x time (all P < 0.001). SHBG curves were different by group and time (P < 0.01), and interaction group x time (P < 0.009). Serum copper, ceruloplasmin, and liver aminotranferases are influenced by estrogens/progesterone, something that should be considered when these indicators are used as outcomes of effects. Time of sampling was also significantly associated with the indicators and deserves further study.