Cited by 13Smoking Behavior and CessationSleep and related disordersChronic Obstructive Pulmonary Disease (COPD) Research

Associations between smoking, sex steroid hormones, trouble sleeping, and depression among U.S. adults: a cross-sectional study from NHANES (2013–2016)

Open access
Huang, Jing, Shi, Peiwen, Zhao, Yuan, Zhang, Huinan, Gao, Tian, Wang, Xing·2024·BMC Public Health

Abstract

Background: Dose-response and nonlinear relationships of cigarette exposure with sleep disturbances and depression are warranted, and the potential mechanism of sex hormones in such associations remains unclear. Methods: Cigarette exposure, trouble sleeping, and depression were assessed by standard questionnaires, and the levels of cotinine and sex steroid hormones were determined among 9900 adults from the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression, logistic regression, and mediation models were conducted to evaluate the associations between smoking, sex steroid hormones, trouble sleeping, and depression. Results: With never smokers as a reference, current smokers had a higher prevalence of trouble sleeping (OR = 1.931, 95% CI: 1.680, 2.219) and depression (OR = 2.525, 95% CI: 1.936, 3.293) as well as testosterone level (β = 0.083, 95% CI: 0.028, 0.140). Pack-years of smoking and cigarettes per day were positively associated with the prevalence of trouble sleeping and depression as well as testosterone level (Ptrend <0.05). The restricted cubic spline model showed linear relationships of cotinine with trouble sleeping, depression, and testosterone. The positive associations of cigarettes per day with trouble sleeping and depression were greater in females than that in males (Pmodification <0.05). However, the potential role of sex hormones was not observed in the association of cotinine with trouble sleeping or depression (Pmediation >0.05). Conclusion: Smoking may induce sex hormone disturbance and increase the risk of sleep problems and depression symptoms, and ceasing smoking may reduce the risk of such complications.

AI snapshot

Written from the paper’s full text.

TL;DR

In a cross-sectional NHANES 2013–2016 sample of 9,900 U.S. adults, current smoking was associated with higher prevalence of trouble sleeping and depression and with higher testosterone levels. Sex steroid hormones did not mediate the associations between cotinine and trouble sleeping or depression.

Key findings

  • With never smokers as reference, current smokers had higher odds of trouble sleeping (OR = 1.931, 95% CI: 1.680, 2.219) and depression (OR = 2.525, 95% CI: 1.936, 3.293), and higher testosterone (β = 0.083, 95% CI: 0.028, 0.140). Former smokers also had higher trouble sleeping (OR = 1.578, 95% CI: 1.368, 1.821) and depression (OR = 1.334, 95% CI: 1.003, 1.773).
  • Pack-years and cigarettes per day were positively associated with trouble sleeping and depression (Ptrend < 0.05). Each 1 cigarette/day increase among current smokers was associated with higher testosterone (+0.5%, 95% CI: 0.2%, 0.7%) and SHBG (+0.3%, 95% CI: 0.1%, 0.6%).
  • Associations of cigarettes per day with trouble sleeping and depression were greater in females than males (Pmodification < 0.05). Restricted cubic spline models showed linear relationships of cotinine with trouble sleeping, depression, and testosterone.
  • Mediation analysis did not identify testosterone, estrogens, or SHBG as mediators between cotinine and trouble sleeping or depression (Pmediation > 0.05; proportion mediated 0.10%–0.40% where calculable).

Methods

  • Cross-sectional analysis of 9,900 adults aged ≥18 from NHANES 2013–2016, the only cycles in which sex steroid hormones were quantified. Smoking exposure was assessed by questionnaire and serum cotinine; testosterone, estrogens, and SHBG were measured in serum; trouble sleeping was self-reported; depression was defined as PHQ-9 score ≥10.
  • Multiple linear regression, logistic regression, restricted cubic spline models, gender-stratified analyses, and mediation models were used. Models adjusted for age, gender, BMI, race, educational qualification, physical activity, alcohol consumption, ratio of family income to poverty, regular periods, and survey cycle; missing values were imputed.
  • Analyses were survey-weighted and performed in R.

Limitations

  • The paper states that the cross-sectional design limits inference on temporality and causality; other covariates such as dietary assessment, genes, and environmental pollutants were not considered; and cotinine and sex steroid hormones are relatively unstable over long periods, so repeated-measures trajectory models are warranted.
  • Evident from the text: trouble sleeping and depression were questionnaire-based rather than clinically diagnosed; smoking exposure and hormone levels were measured at a single time point; mediation analysis cannot establish causal mediation; residual confounding remains possible despite adjustment.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s12889-024-19045-0

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

8 of 11 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    NHANES is a representative cross-sectional survey.

    “The NHANES is a representative cross-sectional survey, which has been described elsewhere [20, 21].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [20] Zhang Y, Mustieles V, Sun Y, Oulhote Y, Wang Y-X, Messerlian C. Association between serum per- and polyfluoroalkyl substances concentrations and common cold among children and adolescents in the United States. Environ Int. 2022;164:107239. source
    • cites [21] Chen C, Ye Y, Zhang Y, Pan X-F, Pan A. Weight change across adulthood in relation to all cause and cause specific mortality: prospective cohort study. BMJ. 2019;367:l5584. source
  • Premisecitation

    Disruption of sex steroid hormones has been found to be associated with multiple adverse health effects, including sleep problems and depression.

    “Disruption of sex steroid hormones has been found to be associated with multiple adverse health effects, including sleep problems and depression [14, 15].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [14] Morssinkhof MWL, van Wylick DW, Priester-Vink S, van der Werf YD, den Heijer M, van den Heuvel OA, Broekman BFP. Associations between sex hormones, sleep problems and depression: a systematic review. Neurosci Biobehav Rev. 2020;118:669–80. source
    • cites [15] Slavich GM, Sacher J. Stress, sex hormones, inflammation, and major depressive disorder: extending Social Signal Transduction Theory of Depression to account for sex differences in mood disorders. Psychopharmacology. 2019;236(10):3063–79. source

      The Introduction (page unavailable) links sex-hormone fluctuations and hormonal transitions with depressed mood and risk for depression. It does not link disruption of sex steroid hormones to sleep problems; searches for sleep and sleep disturbances found no supporting passage. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Findingown data

    The difference in testosterone level between current and former smokers was insignificant.

    “with never smokers as a reference, the level of TST increased by 8.3% (95% CI: 2.8%, 14.0%) in current smokers, whereas the difference with former smokers was insignificant.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported questionnaire assessments of smoking, trouble sleeping, and covariates accurately classify participants.
    • Rests on an assumption: The adjusted covariates are sufficient to control confounding for the associations.
  • Findingown data

    The number of cigarettes per day was positively associated with TST levels.

    “the number of cigarettes per day was positively associated with the TST and SHBG levels”
    Quote in the paperSubstantial claim
  • Findingown data

    The RCS models yielded a linear relationship between serum cotinine concentrations and SHBG levels (P for total < 0.05 and P for nonlinear > 0.05).

    “the RCS models also yielded a linear relationship between serum cotinine concentrations and TST and SHBG levels (figure S3, P for total < 0.05 and P for nonlinear > 0.05).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported questionnaire assessments of smoking, trouble sleeping, and covariates accurately classify participants.
    • Rests on an assumption: The adjusted covariates are sufficient to control confounding for the associations.
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 10
  • Classified as probably not a substantial claim.

    Premisecitation

    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]”
    Quote in the paperSubstantial claim4 of 4 sources checked
    • cites [16] Holmboe SA, Priskorn L, Jensen TK, Skakkebaek NE, Andersson A-M, Jørgensen N. Use of e-cigarettes associated with lower sperm counts in a cross-sectional study of young men from the general population. Hum Reprod. 2020;35(7):1693–701. source

      The Cigarette smoking section reports significantly higher total testosterone in cigarette smokers than non-smokers (P-trend <0.01). The Discussion describes oestradiol as only “slightly higher” in daily smokers and does not establish that this difference was significant. Thus, the claim that both TST and EST were significantly higher overstates the paper. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [17] Kimblad A, Ollvik G, Lindh CH, Axelsson J. Decreased sperm counts in Swedish users of oral tobacco. Andrology. 2022;10(6):1181–8. source

      The Results table (page not available) reports significantly higher testosterone in snuff users than non-users, but it does not compare smokers with non-smokers; the oestradiol difference between snuff groups was not significant (P = 0.19). The Discussion reports a significant positive association of urinary cotinine with both hormones, which lends partial support to the hormone association but does not establish the claimed smoker-versus-non-smoker comparison. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [18] Ihenacho U, Sriprasert I, Mack WJ, Hamilton AS, Unger JB, Press MF, Wu AH. A systematic review and meta-analysis of smoking and circulating sex hormone levels among premenopausal women. Nicotine Tob Res. 2022;24(11):1705–13. source

      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)

      Experimental — accuracy not yet measured
    • cites [19] Shiels MS, Rohrmann S, Menke A, Selvin E, Crespo CJ, Rifai N, Dobs A, Feinleib M, Guallar E, Platz EA. Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men. Cancer Causes Control. 2009;20(6):877–86. source
  • May combine two claims.

    Findingown data

    Smoking status was positively associated with the prevalence of trouble sleeping and depression.

    “smoking status was positively associated with the prevalence of trouble sleeping and depression.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Self-reported questionnaire assessments of smoking, trouble sleeping, and covariates accurately classify participants.
    • Rests on an assumption: The adjusted covariates are sufficient to control confounding for the associations.
    • Rests on an assumption: The single questionnaire item validly measures trouble sleeping.
  • May combine two claims.

    Findingown data

    Females had lower levels of cotinine and TST than males (P < 0.05).

    “Females seemed to have higher levels of BMI, EST, and SHBG, as well as prevalence of trouble sleeping and depression, but lower levels of cotinine and TST than males (P < 0.05).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Among sex steroid hormones, there were very weak positive correlations between TST and EST and between EST and SHBG, and a very weak negative correlation between TST and SHBG.

    “Among sex steroid hormones, very weak positive correlations were presented between TST and EST, and EST and SHBG, whereas a very weak negative correlation was presented between TST and SHBG.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    4728 (47.76%) of the 9900 participants were male.

    “with 4728 (47.76%) male.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The proportions of never, former, and current smokers were 59.89%, 18.79%, and 21.32%, respectively.

    “The proportions for never smokers, former smokers, and current smokers were 59.89%, 18.79%, and 21.32%, respectively.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported questionnaire assessments of smoking, trouble sleeping, and covariates accurately classify participants.
  • May combine two claims.

    Findingown data

    Both former and current smoking were positively associated with the prevalence of depression.

    “In this study, we found that cigarette exposure, both former and current smoking, was positively associated with the prevalence of trouble sleeping and depression”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The mean age of all subjects was 42.68 years (SD 15.11).

    “The mean age of all subjects was 42.68 (standard deviation (SD) 15.11) years”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Females had higher levels of BMI, EST, and SHBG than males (P < 0.05).

    “Females seemed to have higher levels of BMI, EST, and SHBG, as well as prevalence of trouble sleeping and depression, but lower levels of cotinine and TST than males (P < 0.05).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Trouble sleeping and depression rates were 25.49% and 8.17%, respectively.

    “Trouble sleeping and depression rates were 25.49% and 8.17%, respectively.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported questionnaire assessments of smoking, trouble sleeping, and covariates accurately classify participants.
    • Rests on an assumption: The single questionnaire item validly measures trouble sleeping.
  • Classified as probably not a substantial claim.

    Study design and conductown data

    Survey-weighted multiple linear and logistic regression analyses were performed.

    “survey-weighted multiple linear and logistic regression analyses were performed with the “survey” package by R software.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Serum total TST and EST were measured using an ID-LC-MS/MS method that demonstrates high accuracy and precision.

    “The concentrations of serum total TST and EST were measured using isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) method which was created for high sample throughput and demonstrates high accuracy and precision.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A longitudinal study based on 7960 US adolescents showed a positive association between smoking status and the development of sleep problems.

    “A longitudinal study based on 7960 US adolescents showed a positive association between smoking status and the development of sleep problems [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Patten CA, Choi WS, Gillin JC, Pierce JP. Depressive symptoms and cigarette smoking predict development and persistence of sleep problems in US adolescents. Pediatrics. 2000;106(2):E23. source
  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Covariates were adjusted for age, gender, BMI, race, educational qualification, physical activity, alcohol consumption, ratio of family income to poverty, regular periods, and batch (survey cycle) in all models.

    “Covariates were adjusted for age, gender, BMI, race, educational qualification, physical activity, alcohol consumption, ratio of family income to poverty, regular periods, and batch (survey cycle) in all models.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The adjusted covariates are sufficient to control confounding for the associations.
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Cotinine is a major product of nicotine primary metabolism and is a widely used biomarker for the assessment of cigarette exposure, including active and passive smoking.

    “Cotinine, a major product of nicotine primary metabolism, is a widely used biomarker for the assessment of cigarette exposure, including active and passive smoking [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Silva AI, Camelo A, Madureira J, Reis AT, Machado AP, Teixeira JP, Costa C. Urinary cotinine assessment of maternal smoking and environmental tobacco smoke exposure status and its associations with perinatal outcomes: a cross-sectional birth study. Environ Res. 2022;203:111827. source
  • May combine two claims.

    Interpretationown data

    Never smoking or smoking cessation may reduce the risk of depression symptoms.

    “These findings indicate that never smoking or smoking cessation may prevent diseases related to sex hormone disorders and reduce the risk of sleep problems and depression symptoms.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Cotinine and sex steroid hormones in biological samples are relatively unstable over long periods of time.

    “Third, cotinine and sex steroid hormones in biological samples are relatively unstable over long periods of time, and a trajectory model with repeated measurement is warranted.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationown data

    Never smoking or smoking cessation may reduce the risk of sleep problems.

    “These findings indicate that never smoking or smoking cessation may prevent diseases related to sex hormone disorders and reduce the risk of sleep problems and depression symptoms.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Missing values for BMI, educational qualification, ratio of family income to poverty, trouble sleeping, and cotinine were imputed using multiple imputation.

    “Missing values for BMI, educational qualification, ratio of family income to poverty, trouble sleeping, and cotinine were imputed with the use of the multiple imputation approach.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Missing data for the imputed variables are missing at random.
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Other covariates (dietary assessment, gene, environmental pollutants, etc.) that may affect sex steroid hormones, trouble sleeping, and depression were not considered.

    “Second, other covariates (dietary assessment, gene, environmental pollutants, etc.) that may affect sex steroid hormones, trouble sleeping, and depression were not considered.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Reported results for all assays meet the Division of Laboratory Sciences quality control and quality assurance performance criteria for accuracy and precision.

    “Reported results for all assays meet the Division of Laboratory Sciences quality control and quality assurance performance criteria for accuracy and precision.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationown data

    Never smoking or smoking cessation may prevent diseases related to sex hormone disorders.

    “These findings indicate that never smoking or smoking cessation may prevent diseases related to sex hormone disorders and reduce the risk of sleep problems and depression symptoms.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All quality control procedures recommended by the manufacturers were followed for serum cotinine measurement.

    “All quality control procedures recommended by the manufacturers were followed.”
    Quote in the paperNot a substantial claim
23 of 23
  • The paper relies on this without support.

    The observed cross-sectional associations reflect a causal effect of smoking on trouble sleeping, depression, and sex hormones rather than reverse causation or confounding.

    “Smoking may induce sex hormone disturbance and increase the risk of sleep problems and depression symptoms”
  • The paper relies on this without support.

    Self-reported questionnaire assessments of smoking, trouble sleeping, and covariates accurately classify participants.

    “Cigarette exposure, including age started smoking, whether smoking now, time since quitting smoking, cigarettes per day during the past 30 days, and cigarettes per day when smoking cessation, were collected using standard questionnaires.”
  • The paper relies on this without support.

    Missing data for the imputed variables are missing at random.

    “Missing values for BMI, educational qualification, ratio of family income to poverty, trouble sleeping, and cotinine were imputed with the use of the multiple imputation approach.”
  • The paper relies on this without support.

    The adjusted covariates are sufficient to control confounding for the associations.

    “Covariates were adjusted for age, gender, BMI, race, educational qualification, physical activity, alcohol consumption, ratio of family income to poverty, regular periods, and batch (survey cycle) in all models.”
  • The paper relies on this without support.

    The single questionnaire item validly measures trouble sleeping.

    “Trouble sleeping was defined by a questionnaire item “Have you ever told a doctor or other health professional that you have trouble sleeping”.”
  • The paper relies on this without support.

    Serum cotinine concentration is a valid biomarker of cigarette exposure.

    “The mediating effects of sex steroid hormones in the associations between serum cotinine and the prevalence of trouble sleeping and depression are presented in Table 5.”
  • The paper relies on this without support.

    The assumptions required for mediation analysis (such as no unmeasured confounding of the mediator-outcome relationship) hold.

    “The mediating effects of sex steroid hormones in the associations between serum cotinine and the prevalence of trouble sleeping and depression are presented in Table 5.”
7 of 7

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract claims a testosterone trend for pack-years that Table 4 does not show

    Major

    The abstract says pack-years were positively associated with testosterone with Ptrend <0.05, but Table 4 reports a testosterone Ptrend of 0.080 for pack-years.

  • Female current-smoker percentage does not match the count

    Minor

    Table 1 lists 922 current smokers among 5,172 females. That is 17.83%, not the reported 19.18%.

    Reported 19.18 · recomputed 17.826759

  • Reported female testosterone values are below the stated assay limit

    Minor

    The stated testosterone detection limit is 0.750 ng/mL, with lower values replaced by about 0.530 ng/mL (530 ng/L). Yet Table 1 reports a female median of 206 ng/L and quartiles of 141 and 295 ng/L, all below that replacement value.

3 of 3

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Authors
Huang, J., Shi, P., Zhao, Y., Zhang, H., Gao, T., & Wang, X.
Affiliations
Tang Du Hospital (CN)
Corresponding author
  • Gao, Tian
  • Wang, Xing
Venue
BMC Public Health
Published
2024-06-07
Volume
24
Issue
1
Pages
1541-1541
ISSN
1471-2458 (ISSN-L)
OpenAlex
W4399438860
Cited by
13
References
39
Citations by year
2026: 5 · 2025: 5 · 2024: 3
FWCI
3.36
Type
journal article
Language
en
Open access
Locations
  • BMC Public Health (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • the General Project of Key Research and Development Plan of Shaanxi (2023YBSF424)
  • the General Project of Basic Research Plan of Shaanxi (2024JC-YBMS-700)
  • the “Phoenix Introduction Plan” Project of Tangdu Hospital, Air Force Military Medical University (2022YFJH007)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Keywords
cigarette smoking, sex hormones, testosterone, sleep disorders, depression, cotinine, pack-years, sex differences, mediation, dose-response relationship, NHANES
MeSH terms
Adult, Aged, Cotinine, Cross-Sectional Studies, Depression, Female, Humans, Male, Middle Aged, Nutrition Surveys, Gonadal Steroid Hormones, Sleep Wake Disorders, Smoking, Testosterone, United States, Prevalence, Young Adult

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