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Cited by 51Sperm and Testicular FunctionSmoking Behavior and CessationHormonal and reproductive studies

Use of e-cigarettes associated with lower sperm counts in a cross-sectional study of young men from the general population

Open access
Holmboe, Stine Agergaard, Priskorn, Lærke, Jensen, Tina Kold, Skakkebaek, Niels Erik, Andersson, Anna-Maria, Jørgensen, Niels·2020·Human Reproduction
DOI 10.1093/humrep/deaa089
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Abstract

STUDY QUESTION: Are use of e-cigarettes and snuff associated with testicular function as previously shown for conventional cigarettes and marijuana? SUMMARY ANSWER: Use of e-cigarettes is associated with reduced semen quality but not with higher serum testosterone level as observed for conventional cigarette use. Snuff use was not associated with markers of testicular function. WHAT IS KNOWN ALREADY: Cigarette smoking has previously been associated with higher testosterone levels and impaired semen quality, whereas it is unresolved whether use of e-cigarettes or snuff influence the testicular function. STUDY DESIGN, SIZE, DURATION: This cross-sectional population-based study included 2008 men with information on cigarette and marijuana use (enrolled between 2012 and 2018), among whom 1221 men also had information on e-cigarette and snuff use (enrolled between 2015 and 2018). PARTICIPANTS/MATERIALS, SETTING, METHODS: Men (median age 19.0 years) from the general population provided a semen and blood sample and filled out a questionnaire on lifestyle including information on smoking behaviour. Associations between different types of smoking (e-cigarettes, snuff, marijuana and cigarettes) and reproductive hormones (total and free testosterone, sex hormone-binding globulin, LH, oestradiol and ratios of inhibin B/FSH, testosterone/LH and free testosterone/LH) and semen parameters (total sperm count and sperm concentration) were examined using multiple linear regression analyses adjusted for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Approximately half of the men (52%) were cigarette smokers, 13% used e-cigarettes, 25% used snuff and 33% used marijuana. Users of e-cigarettes and marijuana were often also cigarette smokers. Compared to non-users, daily e-cigarette users had significantly lower total sperm count (147 million vs 91 million) as did daily cigarette smokers (139 million vs 103 million), in adjusted analyses. Furthermore, significantly higher total and free testosterone levels were seen in cigarette smoking men (6.2% and 4.1% higher total testosterone and 6.2% and 6.2% higher free testosterone in daily smokers and occasional smokers, respectively, compared to non-smoking men), but not among e-cigarette users. Daily users of marijuana had 8.3% higher total testosterone levels compared to non-users. No associations were observed for snuff in relation to markers of testicular function. LIMITATIONS, REASONS FOR CAUTION: We cannot exclude that our results can be influenced by residual confounding by behavioural factors not adjusted for. The number of daily e-cigarette users was limited and findings should be replicated in other studies. WIDER IMPLICATIONS OF THE FINDINGS: This is the first human study to indicate that not only cigarette smoking but also use of e-cigarettes is associated with lower sperm counts. This could be important knowledge for men trying to achieve a pregnancy, as e-cigarettes are often considered to be less harmful than conventional cigarette smoking. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the Danish Ministry of Health (1-1010-308/59), the Independent Research Fund Denmark (8020-00218B), ReproUnion (20200407) and the Research Fund of the Capital Region of Denmark (A6176). The authors have nothing to disclose. TRIAL REGISTRATION NUMBER: NA

AI snapshot

Written from the paper’s full text.

TL;DR

In a cross-sectional study of young Danish men from the general population, daily e-cigarette use was associated with lower sperm counts, similar in magnitude to daily cigarette smoking, but without the higher testosterone levels seen with cigarette smoking. Snuff use was not associated with markers of testicular function.

Key findings

  • Daily e-cigarette users had lower total sperm count than non-users (91 million vs 147 million) and lower sperm concentration (33 million/ml vs 45 million/ml) in adjusted analyses; daily cigarette smokers also had lower total sperm count (103 million vs 139 million) and sperm concentration (33 million/ml vs 44 million/ml).
  • Cigarette smoking was associated with higher total testosterone (6.2% higher in daily smokers and 4.1% higher in occasional smokers vs non-smokers) and higher free testosterone (6.2% higher in both daily and occasional smokers vs non-smokers); e-cigarette users did not show higher testosterone.
  • Daily marijuana users had 8.3% higher total testosterone than non-users, but no differences in sperm counts across marijuana use groups in main analyses.
  • Snuff use showed no associations with reproductive hormones or semen quality.

Methods

  • Cross-sectional population-based study of 2008 men with information on cigarette and marijuana use (enrolled 2012–2018), of whom 1221 also had information on e-cigarette and snuff use (enrolled 2015–2018); median age was 19.0 years.
  • Participants completed a questionnaire, provided a semen sample and blood sample, and underwent physical examination; smoking categories were non-users, occasional users, and daily users.
  • Associations with reproductive hormones and semen parameters were examined using multiple linear regression adjusted for examination year, BMI, alcohol intake, self-rated physical fitness, and daily cigarette smoking for non-cigarette exposures; hormone outcomes also adjusted for time of blood sampling, and sperm outcomes for abstinence period.

Limitations

  • The authors state that residual confounding by behavioural factors not adjusted for cannot be excluded, that the number of daily e-cigarette users was limited, and that findings should be replicated.
  • The text also makes evident that the cross-sectional design precludes causal inference, smoking exposure was questionnaire-based without objective measures such as cotinine, and categorization into daily/occasional/non-users was crude.
  • Frequent co-use of smoking products limited analyses of single-users, and because most daily e-cigarette users reported nicotine-containing e-liquid, the impact of daily nicotine-free e-cigarette use could not be examined.

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

Integrity signals

Registry

Crossref · 10.1093/humrep/deaa089

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

6 of 33 cited sources checked · 5 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    In a Swedish study of men comparable to those in the present study, snuff was not associated with reproductive parameters.

    “Nor was snuff associated with reproductive parameters in a Swedish study of men comparable to those in the present study (Richthoff et al., 2008).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Richthoff et al., 2008 source
  • Findingown data

    In the main analyses, we observed no differences in sperm counts in daily or occasional users of marijuana compared to non-users.

    “In our main analyses, we observed no differences in sperm counts in daily or occasional users of marijuana compared to nonusers.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Cigarette smoking is associated with lower total sperm count compared to non-smoking.

    “total sperm counts (103 million, 136 million and 139 million for daily smokers, occasional smokers and non-smokers, respectively, P-trend <0.01) in adjusted analyses”
    • Also stated in: § Abstract · plain
      “daily cigarette smokers (139 million vs 103 million)”
    Quote in the paperSubstantial claim
  • Findingown data

    The majority of daily e-cigarette users reported that the e-liquid contained nicotine.

    “The majority of daily e-cigarette users reported that the e-liquid contained nicotine and thus, the impact of daily e-cigarette use without nicotine content could not be examined.”
    Quote in the paperSubstantial claim
  • Findingown data

    Cigarette smoking is associated with higher free testosterone levels compared to non-smoking.

    “6.2% and 6.2% higher free testosterone in daily smokers and occasional smokers, respectively, compared to non-smoking men”
    • Also stated in: § Cigarette smoking · plain
      “6.2% and 6.2% higher free testosterone level (P-trend <0.01)”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 42
  • May combine two claims. 17

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Marijuana users have higher testosterone levels compared to men with no use.

    “Recent studies on marijuana use and testicular function indicate that also marijuana users have higher testosterone levels compared to men with no use (Gundersen et al., 2015;Nassan et al., 2019).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Gundersen et al., 2015 source
    • cites Nassan et al., 2019 source

      The Results report no association between marijuana-smoking status and reproductive hormone concentrations other than FSH, contrary to the claimed testosterone difference between users and never-users. They do report higher testosterone with more intense use, but that analysis was restricted to men who had smoked marijuana and did not compare them with never-users. (LLM, conf=0.85)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Male cigarette smokers have higher testosterone levels compared to non-smokers.

    “It is well known that male cigarette smokers have higher testosterone levels compared to non-smokers, however, the mechanism behind this is debated (Shiels et al., 2009;Holmboe et al., 2015).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Shiels et al., 2009 source
    • cites Holmboe et al., 2015 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Among American sub-fertile men, marijuana users were characterized by higher sperm concentration and total sperm count compared to never users.

    “whereas among American sub-fertile men, marijuana users were characterized by higher sperm concentration and total sperm count compared to never users (Nassan et al., 2019).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Nassan et al., 2019 source

  • May combine two claims.

    Premisecitation

    It has previously been shown that testosterone levels were different for smokers and non-smokers but within the group of smokers, testosterone levels did not differ according to number of cigarettes smoked per day.

    “However, it has previously been shown that testosterone levels were different for smokers and non-smokers but within the group of smokers, testosterone levels did not differ according to number of cigarettes smoked per day (Shiels et al., 2009)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Shiels et al., 2009 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Use of multiple nicotine products is frequent, with the most common combination being cigarettes and e-cigarettes.

    “Use of multiple nicotine products is frequent, with the most common combination being cigarettes and e-cigarettes (Agaku et al., 2014;Kasza et al., 2017).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Agaku et al., 2014 source
    • cites Kasza et al., 2017 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In our study, 33% of daily e-cigarette users were co-using cigarettes.

    “which is in accordance with our study (33%).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Users of e-cigarettes and marijuana were often also cigarette smokers.

    “Users of e-cigarettes and marijuana were often also cigarette smokers.”
    • Also stated in: § Basic characteristics · plain
      “Users of other smoking types frequently also smoked cigarettes corresponding to 33% of e-cigarette users, 9% of snuff users and 71% of marijuana users (Fig. 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Daily marijuana users had higher free testosterone levels compared to non-smokers (6.2% higher, P-trend = 0.29).

    “and 6.2% higher free testosterone level compared to non-smokers (P-trend ¼ 0.29).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared to non-users, users of e-cigarettes (adjusted for cigarette smoking) had lower sperm concentration and total sperm count.

    “we observed that compared to non-users, both daily cigarette smokers and users of e-cigarettes (adjusted for cigarette smoking) were characterized by lower sperm concentration and total sperm count with effect sizes of similar magnitude.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    We observed frequent co-use of smoking products with cigarette smoking being the most frequent one.

    “In general, we observed frequent co-use of smoking products with cigarette smoking being the most frequent one”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In sensitivity analyses using the alternative categorization, weekly users, but not daily users, were characterized by lower sperm counts.

    “However, in sensitivity analyses using the alternative categorization, weekly users, but not daily users, were characterized by lower sperm counts (Supplementary Fig. S1)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Supplementary Fig. S1

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    In the present study, median alcohol intake in daily users of marijuana was similar to that of non-users (5 units per week and 4 units per week, respectively), whereas the median alcohol intake for occasional users was 10 units per week.

    “In fact, in the present study, median alcohol intake in daily users of marijuana was similar to that of non-users (5 units per week and 4 units per week, respectively), whereas the median alcohol intake for occasional users was 10 units per week.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    The finding that e-cigarette use is associated with lower sperm counts could be important knowledge for clinicians and men trying to achieve a pregnancy as e-cigarettes are often considered to be less harmful than conventional cigarette smoking.

    “This could be important knowledge for clinicians and men trying to achieve a pregnancy as e-cigarettes are often considered to be less harmful than conventional cigarette smoking.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In adult rats, exposure to e-cigarette liquid with tobacco flavour, with or without nicotine, reduced sperm concentration and caused histopathological changes in the testes.

    “Compared to controls, adult rats exposed to e-cigarette liquid with tobacco flavour with or without nicotine both showed reduced sperm concentration and histopathological changes in the testes suggesting adverse effects of the e-liquid per se.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites El Golli et al., 2016 source
    • cites Rahali et al., 2018 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a small group of men attending a fertility clinic, use of snuff was adversely related to semen quality.

    “In a small group of men (n ¼ 62) attending a fertility clinic, use of snuff was adversely related to semen quality (Pa ¨rn et al., 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pärn et al., 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    We adjusted for cigarette smoking in fully adjusted models.

    “and, for that reason, we adjusted for cigarette smoking in fully adjusted models.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Men using smokeless tobacco have higher testosterone levels compared to men with no use.

    “As seen for conventional cigarette smoking men, it has been observed that men using smokeless tobacco have higher testosterone levels compared to men with no use (Shah et al., 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shah et al., 2019 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Due to lack of power regarding number of single-users, it was not possible to study effects of different types of smoking in larger groups of single-users only to eliminate the effect from coexposure.

    “Due to lack of power regarding number of single-users, this was however not possible in the present study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Detailed information on potentially related lifestyle factors was obtained, and the men were unaware of their testis function at time of recruitment.

    “Furthermore, detailed information on potentially related lifestyle factors was obtained, and the men were unaware of their testis function at time of recruitment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    The categorization into daily, occasional and non-users is a rather crude categorization but could be used consistently across the different smoking types.

    “Furthermore, the categorization into daily, occasional and non-users is a rather crude categorization but on the other hand, these categories could be used consistently across the different smoking types.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Findings were reported according to STROBE guidelines.

    “Findings were reported according to STROBE guidelines.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a study of young Danish men, regular users of marijuana had a lower sperm concentration and total sperm count compared to men with no use.

    “In a study of young Danish men, similar to the population in the present study but with no overlap between cohorts, regular users of marijuana had a lower sperm concentration and total sperm count compared to men with no use (Gundersen et al., 2015)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gundersen et al., 2015 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In adjusted regression models, we adjusted for alcohol intake.

    “In adjusted regression models, we adjusted for alcohol intake”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Maternal cigarette smoking during pregnancy is negatively associated with semen quality in offspring.

    “Maternal cigarette smoking during pregnancy is also negatively associated with semen quality in offspring (Storgaard et al., 2003;Jensen et al., 2004;Ramlau-Hansen et al., 2007;Ravnborg et al., 2011).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Storgaard et al., 2003 source
    • cites Jensen et al., 2004 source
    • cites Ramlau-Hansen et al., 2007 source

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study adjusted for relevant confounders in multiple linear regression analyses.

    “were examined using multiple linear regression analyses adjusted for relevant confounders.”
    • Also stated in: § Statistical analyses · plain
      “Adjusted models all included examination year (continuous variable), BMI (continuous variable), units of alcohol the week prior to study participation (continuous variable) and self-rated physical fitness (poor, fair and good).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    An association between e-cigarette use and testosterone cannot be excluded based on the present study, which had limited power.

    “However, an association between e-cigarette use and testosterone cannot be excluded based on the present study, which had limited power.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies show conflicting results regarding marijuana use and semen quality.

    “However, the studies show conflicting results regarding semen quality.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    This is the first human study to indicate that not only cigarette smoking but also use of e-cigarettes is associated with lower sperm counts.

    “This is the first human study to indicate that not only cigarette smoking but also use of e-cigarettes is associated with lower sperm counts.”
    • Also stated in: § Discussion · hedged
      “This is the first human study to indicate that not only cigarette smoking but also use of e-cigarettes is associated with lower sperm counts, although the mechanisms are unknown.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: No human studies have investigated the association between use of e-cigarettes and reproductive function.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In fully adjusted analyses, individuals with missing data on one or more of the included covariates were excluded (<3.5%).

    “In fully adjusted analyses, individuals with missing data on one or more of the included covariates were excluded (<3.5%).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The overall participation rate was 25%.

    “The overall participation rate was 25% (Priskorn et al., 2018).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Priskorn et al., 2018 source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Semen analysis was conducted according to World Health Organization guidelines.

    “The semen sample was kept at 37 C until analysis, which was conducted according to the World Health Organization (WHO) guidelines ( World Health Organization, 2010 ).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites World Health Organization, 2010

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Exposed rats showed lower plasma testosterone levels.

    “Exposed rats also showed lower plasma testosterone levels (El Golli et al., 2016;Rahali et al., 2018)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites El Golli et al., 2016 source
    • cites Rahali et al., 2018 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    PAHs are a class of ubiquitous toxic compounds produced by the incomplete combustion of organic materials and are highly present in tobacco smoke.

    “PAHs are a class of ubiquitous toxic compounds produced by the incomplete combustion of organic materials and accordingly are highly present in tobacco smoke (Suwan-ampai et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Suwan-ampai et al., 2009 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The mechanisms behind the association between e-cigarette use and lower sperm counts are unknown.

    “although the mechanisms are unknown.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several PAHs have been shown to exert antiandrogenic effects by modifying human androgen receptor activation.

    “Furthermore, several PAHs have been shown to exert antiandrogenic effects by modifying human androgen receptor activation (Vinggaard et al., 2000).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Vinggaard et al., 2000 source

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Analyses with primary exposure other than cigarettes were adjusted for daily cigarette smoking.

    “Analyses with primary exposure other than cigarettes were furthermore adjusted for daily cigarette smoking (yes/no).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    A strength of the study is the rather large sample size with information on various smoking behaviours, although the number of daily e-cigarette users was limited.

    “A strength of the study is the rather large sample size with information on various smoking behaviours, although the number of daily e-cigarette users was limited.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    We cannot exclude that our results can be influenced by residual confounding by behavioural factors not adjusted for.

    “We cannot exclude that our results can be influenced by residual confounding by behavioural factors not adjusted for.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A population-based study including 1102 adult men from NHANES observed that urinary PAH metabolites were positively associated with higher total testosterone level.

    “In line with this, a population-based study including 1102 adult men from NHANES (Wang et al., 2017) observed that urinary PAH metabolites were positively associated with higher total testosterone level.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang et al., 2017 source

  • Classified as probably not a substantial claim.

    Interpretationown data

    If nicotine was the cause of higher testosterone, higher testosterone would be expected in e-cigarette users.

    “which would be expected if nicotine was the cause of higher testosterone.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    A competitive inhibition of the binding of testosterone to the androgen receptor by PAHs could lead to an attenuated negative feedback of circulating testosterone on LH release, resulting in an increase of LH and subsequently higher circulating testosterone levels, which could explain the observed higher levels of testosterone in smoking men.

    “Thus, a competitive inhibition of the binding of testosterone to the androgen receptor by PAHs could lead to an attenuated negative feedback of the circulating testosterone on the LH release, resulting in an increase of LH, and subsequently higher circulating testosterone levels which could explain the observed higher levels of testosterone in smoking men.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    We cannot rule out that our results can be influenced by confounding by behavioural factors not included in the statistical analyses, including information on previous smoking habits.

    “and furthermore we cannot rule out that our results can be influenced by confounding by behavioural factors not included in the statistical analyses, including information on previous smoking habits.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Regression analyses were checked for interaction between cigarette smoking and each of the other products.

    “Regression analyses were checked for interaction between cigarette smoking and each of the other products by including the interaction term in the adjusted models and furthermore by stratifying on daily cigarette smoking (yes/no) due to the frequent co-use of this product.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cigarette smoking has a negative impact on semen quality.

    “Furthermore, findings from a recent meta-analysis indicated that cigarette smoking has a negative impact on semen quality (Sharma et al., 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sharma et al., 2016 source

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Covariates were selected a priori based on the literature using causal diagrams.

    “Covariates were selected a priori based on the literature using causal diagrams including potential confounders for the association (lifestyle factors) as well as covariates closely related to variation in the outcome measurements (time of blood sampling, period of abstinence and examination year).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Data on e-cigarette and snuff use was available from 2015 and onwards, leaving 1221 men in these analyses.

    “Data on e-cigarette and snuff use was available from 2015 and onwards, leaving 1221 men in these analyses.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    A total of 2017 men participated between 2012 and 2018, but nine men were excluded due to current use of anabolic steroids leaving 2008 men eligible for analyses.

    “A total of 2017 men participated between 2012 and 2018, but nine men were excluded from the present study due to current use of anabolic steroids (self-reported or indicated from reproductive hormone profile) leaving 2008 men eligible for analyses.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In vitro studies of testis tissue from fish have shown an inverse U-shaped association between PAH levels and testosterone levels, indicating that lower doses of PAH can have a stimulatory effect on testosterone production, whereas inhibition was seen at high doses.

    “In vitro studies of testis tissue from fish have shown an inverse U-shaped association between PAH levels and testosterone levels, indicating that lower doses of PAH can have a stimulatory effect on testosterone production, whereas inhibition was seen at high doses (Evanson and Van Der Kraak, 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Evanson and Van Der Kraak, 2001 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The difference in findings between the previous study and the present study could be explained by daily and weekly use being categorized into the same group in the previous study.

    “which could explain the differences in findings as daily and weekly use was categorized into the same group in the previous study.”
    Quote in the paperNot a substantial claim
49 of 49

  • The authors state this as an assumption.

    No human studies have investigated the association between use of e-cigarettes and reproductive function.

    “To our knowledge, no human studies have investigated the association between use of ecigarettes and reproductive function”

  • The authors state this as an assumption.

    The included men represent the general population in their age group regarding reproductive function and smoking habits.

    “The included men are assumed to represent the general population in their age group regarding reproductive function and smoking habits.”

  • The paper relies on this without support.

    The literature on reproductive effects of e-cigarette use is very limited.

    “The literature on reproductive effects of e-cigarette use is very limited.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Numerous studies have examined the impact of smoking on male reproductive hormone levels, yielding conflicting results.

    “Numerous studies have examined the impact of smoking on male reproductive hormone levels, yielding conflicting results.”

    From Association between serum cotinine and total testosterone in adult males based on NHANES 2011–2016 (2024) · cites this paper as [17]

    The Introduction (page unavailable) cites several studies of cigarette smoking and male hormone levels, supporting that the topic has been studied. It does not characterize their hormone findings as conflicting; instead, it says smokers are well known to have higher testosterone levels, and the Discussion says this study’s findings accord with other population-based studies. The Introduction’s reference to conflicting results concerns marijuana and semen quality, not smoking and hormones. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • 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 [16]

    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

  • A study in Danish men found that both daily cigarette and e-cigarette users had decreased sperm counts.

    “A similar result was found in Danish men (of whom 68 used snuff daily), in whom both daily cigarette and e‐cigarette users had decreased sperm counts. 7”

    From Decreased sperm counts in Swedish users of oral tobacco (2022) · cites this paper as [7]

  • No association was found between snuff use and reproductive hormones in the Richthoff and Danish studies.

    “No association was found between snuff use and reproductive hormones in either of these two studies.”

    From Decreased sperm counts in Swedish users of oral tobacco (2022) · cites this paper as [7]

  • Our article included a higher number of snuff-users than the articles by Pärn et al., Richthoff et al., and Holmboe et al., and thus possibly had a greater statistical power.

    “In comparison to the articles by Pärn et al., 8 Richthoff et al. 16 and Holmboe et al., 7 our article included a higher number of snuff‐users, and thus possibly had a greater statistical power.”

    From Decreased sperm counts in Swedish users of oral tobacco (2022) · cites this paper as [7]

Self-check

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

  • Daily cigarette smokers' sexually transmitted disease percentage does not match its count

    Minor

    The reported 53 men among 467 daily cigarette smokers represent 11.3%, not 11.1%. A smaller denominator due to missing responses would make the percentage higher, not lower.

    Reported 11.1 · recomputed 11.349036

  • Overall good-physical-fitness percentage does not match its count

    Minor

    Table I reports 1126 men with good physical fitness among 2008 participants, which is 56.1%, not 55.1%.

    Reported 55.1 · recomputed 56.075697

2 of 2

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1016/j.addbeh.2018.12.028

    Major

    The cited work was retracted on 2019-04-22 (notice 10.1016/j.addbeh.2019.04.013), before this paper was published (2020-06-19). Its authors could have known.

    Cited work 10.1016/j.addbeh.2018.12.028 · retracted 2019-04-22 · notice 10.1016/j.addbeh.2019.04.013 · this paper published 2020-06-19

1 of 1

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. 2010, WHO laboratory manual for the Examination and processing of human semen

Cited by

Sorted by citations

Related

Authors
Holmboe, S. A., Priskorn, L., Jensen, T. K., Skakkebaek, N. E., Andersson, A.-M., & Jørgensen, N.
Affiliations
  • University of Copenhagen (DK)
  • Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark
Corresponding author
Holmboe, Stine Agergaard
ORCID
Venue
Human Reproduction
Publisher
Oxford University Press (OUP)
Published
2020-06-19
Volume
35
Issue
7
Pages
1693-1701
ISSN
  • 0268-1161 (ISSN-L)
  • 1460-2350
DOI
10.1093/humrep/deaa089
OpenAlex
W3035893856
Cited by
51
References
30
Citations by year
2026: 10 · 2025: 10 · 2024: 10 · 2023: 10 · 2022: 3 · 2021: 6 · 2020: 2
FWCI
4.50
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Human Reproduction (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
Funders
  • Danish Ministry of Health (1-1010-308/59)
  • Independent Research Fund Denmark (8020-00218B)
  • ReproUnion (20200407)
  • Research Fund of the Capital Region of Denmark (A6176)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
electronic cigarettes, snuff, sperm count, semen quality, testicular function, testosterone, reproductive hormones, cannabis, cigarette smoking, young men, sex hormone-binding globulin, inhibin B, luteinizing hormone, estradiol, tobacco use
MeSH terms
Adult, Cross-Sectional Studies, Female, Humans, Male, Pregnancy, Sperm Count, Spermatozoa, Testosterone, Semen Analysis, Young Adult, Electronic Nicotine Delivery Systems

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-05.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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