Cigarette smoking and testosterone in men and women: A systematic review and meta-analysis of observational studies

• Nicotine and/or its metabolites could competitively inhibit androgen disposal.
• Smoking would be expected to increase testosterone.
• Smoking was associated with higher testosterone among men.
• Nicotine products, e.g., e-cigarettes, may raise testosterone.

Recently Health Canada and the Food and Drug Administration warned about the cardiovascular risk of testosterone, making environmental drivers of testosterone potential prevention targets. Cotinine, a tobacco metabolite, inhibits testosterone breakdown. We assessed the association of smoking with testosterone in a systematic review and meta-analysis, searching PubMed and Web of Science through March 2015 using (“testosterone” or “androgen” or “sex hormone”) and (“smoking” or “cigarette”). Two reviewers independently searched, selected, assessed quality and abstracted with differences resolved by consensus or reference to a third reviewer. The initial search yielded 2881 studies; 28 met the selection criteria. In 22 studies of 13,317 men, mean age 18–61 years, smokers had higher mean testosterone than non-smokers (1.53 nmol/L, 95% confidence interval (CI) 1.11 to 1.96) using a random effects model with inverse variance weighting. In 6 studies of 6089 women, mean age 28–62 years, smoking was not clearly associated with testosterone (0.11 nmol/L, 95% CI − 0.08 to 0.30). Fixed effects models provided similar results, but suggested a positive association in women. Whether products which raise cotinine, such as e-cigarettes or nicotine replacement, also raise testosterone, should be investigated, to inform any regulatory action for e-cigarettes, which emit nicotine into the surrounding air, with relevance for both active and passive smokers.