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A Systematic Review and Meta-Analysis of Smoking and Circulating Sex Hormone Levels Among Premenopausal Women

Ihenacho, Ugonna, Sriprasert, Intira, Mack, Wendy J, Hamilton, Ann S, Unger, Jennifer B, Press, Michael F, Wu, Anna H·2022·Nicotine & Tobacco Research
DOI 10.1093/ntr/ntac066
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Abstract

Introduction: It is established that higher prediagnostic circulating androgen and estrogen levels are associated with increased breast cancer risk in premenopausal and postmenopausal women. Pooled analyses in postmenopausal women report higher androgen and estrogen levels in current heavy cigarette smokers compared to nonsmokers. However, evidence among premenopausal women has been inconsistent. Aims and Methods: We conducted a systematic review and meta-analysis to estimate differences in standardized mean hormone levels among current premenopausal smokers compared to nonsmokers. We reviewed and collated publications with sex hormone levels by smoking status among healthy, premenopausal women who were nonusers of exogenous hormones, including oral contraceptives, using PubMed through December 2019. A random effects meta-analysis was conducted to combine the standardized mean differences (SMD) and 95% confidence intervals (CIs) for estradiol, progesterone, testosterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and sex hormone-binding globulin by smoking status. Findings were summarized by menstrual cycle phase and overall. Results: Nineteen published peer-reviewed articles were included. Significantly increased testosterone levels among smokers compared to nonsmokers were identified from cross-sectional studies with varied menstrual phase timing (SMD 0.14; 95% CI 0.0005, 0.29) and significantly increased dehydroepiandrosterone-sulfate levels were found over all phases (SMD 0.12; 95% CI 0.01, 0.22). However, substantial heterogeneity existed in these studies. Conclusions: This meta-analysis suggests that smoking may increase blood androgen levels in healthy premenopausal women which may increase breast cancer risk; however, the differences were modest. Larger and covariate-adjusted studies with standardized collection over the menstrual cycle are needed to better understand this relationship and to reduce heterogeneity. Implications: Existing research has described associations between high prediagnostic estradiol and androgen levels with breast cancer risk among premenopausal women and has established active smoking as a breast cancer risk factor. However, the smoking and circulating sex hormone associations among premenopausal women remain inadequately studied. In this meta-analysis, we identified an association between smoking and higher mean testosterone and dehydroepiandrosterone-sulfate levels with consideration of menstrual phase, providing additional information on smoking’s potential pathway to premenopausal breast cancer.

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  • Previous studies have shown that smokers have significantly higher levels of TST and EST than non-smokers.

    “previous studies have shown that smokers have significantly higher levels of TST and EST than non-smokers [16–19]”

    From Associations between smoking, sex steroid hormones, trouble sleeping, and depression among U.S. adults: a cross-sectional study from NHANES (2013–2016) (2024) · cites this paper as [18]

    The Association between smoking and hormone levels section (p. 13) reports significantly higher testosterone only in the subgroup with varied sample-collection timing; the overall testosterone difference was not significant. The same section (p. 12) reports no significant overall difference in estradiol between smokers and nonsmokers, so the claim that both hormones are significantly higher is not supported for the premenopausal women studied. (LLM, conf=0.90)

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Authors
Ihenacho, U., Sriprasert, I., Mack, W. J., Hamilton, A. S., Unger, J. B., Press, M. F., & Wu, A. H.
Affiliations
  • Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California , Los Angeles, CA , USA
  • Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California , Los Angeles, CA , USA
  • Department of Pathology, Keck School of Medicine, University of Southern California , Los Angeles, CA , USA
ORCID
Venue
Nicotine & Tobacco Research
Publisher
Oxford University Press (OUP)
Published
2022-03-15
Volume
24
Issue
11
Pages
1705-1713
ISSN
1469-994X
DOI
10.1093/ntr/ntac066
Cited by
19
References
2
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Funders
  • Tobacco-Related Disease Research Program
  • University of California (T29DT0375)
  • Breast Cancer Research Foundation (BCRF-21-132)
  • Tower Cancer Research Foundation (006886-0001)

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