Use of E-Cigarettes Associated With Lower Sperm Counts in a Cross-Sectional Study of Young Men From the General Population

Stine Agergaard Holmboe; Lærke Priskorn; Tina Kold Jensen; Niels Erik Skakkebaek; Anna-Maria Andersson; Niels Jørgensen

Disclosures

Hum Reprod. 2020;35(7):1693-1701. 

In This Article

Abstract and Introduction

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

Introduction

It is estimated that more than 30% of the adult male population use tobacco products with the main type being cigarettes (World Health Organization, 2015). During the past decades, a decline in proportion of tobacco smokers has been observed in the Western world (Islami et al., 2015). However, this decline has to some degree been paralleled by an increase in use of other types of tobacco products, especially among the young generations (Mantey et al., 2019). Alternative tobacco products include smokeless and sometimes flavoured tobacco products such as electronic-cigarettes (e-cigarettes) and snuff. 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).

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). Furthermore, findings from a recent meta-analysis indicated that cigarette smoking has a negative impact on semen quality (Sharma et al., 2016). 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). 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). However, the studies show conflicting results regarding semen quality. 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), 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). Few studies have investigated the association between male reproductive function and alternative tobacco products. In a small group of men (n = 62) attending a fertility clinic, use of snuff was adversely related to semen quality (Pärn et al., 2015). 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). To our knowledge, no human studies have investigated the association between use of e-cigarettes and reproductive function; however, animal studies have shown that intraperitoneal exposure to e-cigarette liquids was associated with impaired testis function including decreased testosterone levels independent of containing nicotine or not (El Golli et al., 2016; Rahali et al., 2018).

Thus, using a cohort of young men from the general population with information on use of various types of smoking/tobacco products, the aim of this study was to investigate whether use of e-cigarettes as well as other smoking habits were associated with reproductive hormone levels and semen quality.

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