Relevance of serum copper elevation induced by oral contraceptives: a meta-analysis

Contraception. 2013 Jun;87(6):790-800. doi: 10.1016/j.contraception.2012.10.006. Epub 2012 Nov 13.


Background and study design: It is well documented that copper (Cu) blood levels are elevated in combination oral contraceptive (COC) users. The aim of this study was to establish the range of Cu increase in OC users compared to nonusers through a systematic literature overview and quantitative data analysis.

Results: Twenty-six articles were included in the meta-analysis. The increase in Cu level exponentially decreased in COC users over time, with a rapid decline through the 1960s and 1970s. After controlling for the publication year, use of COC increases the mean serum/plasma Cu level by 0.57 mg/L (95% confidence interval 0.49-0.66 mg/L).

Conclusion: COCs commonly raise serum Cu to levels between 1.5 and 2 mg/L, which are above reference levels. Although these levels are not considered toxic, there are suggestions that such Cu increase could be implicated in oxidative pathophysiological processes in the body. Further research on safety of COCs use, including oxidative-stress-related effects, is warranted.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Contraceptives, Oral / administration & dosage
  • Contraceptives, Oral / adverse effects*
  • Copper / blood*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Reproducibility of Results
  • Up-Regulation / drug effects*


  • Contraceptives, Oral
  • Copper