Aim: This study compared semen quality, FSH, LH, and Testosterone levels in infertile males among smokers and non-smokers and semen quality among alcoholics and non alcoholics.

Methods: A literature search was conducted across five databases in December 2021. The search for this article uses specific keywords tailored to each search database’s specifications.

Results: A total of 15 studies with 12,503 infertile male participants included in this study. 8,025 were non-smokers, 4,477 were smokers, 210 were alcoholics and 407 were non alcoholics. The effect of tobacco smoking on sperm were more significant in smokers than in non-smokers. Alcohol consumption affects the quality and quantity of semen. Both tobacco smoking and alcohol consumption combined may amplify their negative effects toward semen parameters.

Conclusion: Smoking and alcohol has a detrimental impact on conventional semen characteristics. Due to the harmful effects of both factors, men seeking reproduction should be advised to avoid these habits.

Tobacco smoking, alcohol consumption, semen quality, infertile male, reproductive hormones

Infertility refers to the incapacity of a sexually active couple who do not use contraception to naturally conceive a child within a year, where it can be primary, meaning no previous pregnancies; or secondary, meaning previous successful conceptions but subsequent difficulties. (Bundhun et al. 2019). According to the World Health Organization (WHO), Infertility impacts 48 million couples globally, affecting a total of 186 million individuals across the world. Infertility is a common problem for 8–15% of couples globally and 10–15% of couples in developed countries (Rowe et al. 2000).

In 30–40% of cases, the cause of male infertility remains unknown (idiopathic male infertility), although semen analysis may show abnormalities in the sperm quality (Bundhun et al. 2019). Lifestyle factors that may increase the risk of male infertility include occupational and behavioral factors, including diet, obesity, smoking, alcohol consumption, recreational drug use, and exposure to environmental toxins (Meri et al. 2013). Many studies have proved that cigarette smoking negatively impacts the reproductive systems and fertility of both men and women. The prevalence of smoking is about 37% in men who are in their reproductive age (Tang et al. 2019). These studies indicated that tobacco smoking decreases sperm count, motility, and normal morphology (Rehman et al. 2019 and Mokhtari et al. 2020). However, some studies did not find significant differences in conventional sperm parameters between smokers and non-smokers. Davar et al. 2020 study noted that smokers exhibited reduced semen parameters, including morphology, motility, and concentration. However, these differences among the groups did not reach statistical significance (Davar et al. 2012). Male infertility linked to chronic alcohol use may also result from altered gene expression regulation, affecting the metabolism of proteins crucial for sperm maturation (Finelli et al. 2021). Research by Jensen et al. discovered negative associations between habitual alcohol intake and sperm concentration, total sperm count, and the percentage of sperm with normal morphology (Jensen et al. 2014).

The impact factors on semen quality is still a matter of debate. Therefore, our aim was to assess semen parameters in both individuals who smoke and those who do not, and to examine the impact of tobacco smoking on semen quality, as well as the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone in males experiencing infertility.

The review was done based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. This study aims to analyze the effect of tobacco smoking and alcohol consumption on semen quality in infertile male, so the Patient Interventions Comparisons Outcomes (PICO) used in this systematic review were:

Patients : Infertile male

Interventions : Tobacco smoking and alcohol consumption

Comparisons : -

Outcomes : Semen quality, FSH, LH, Testosteron

Infertility can be influenced by a multitude of factors, encompassing congenital or acquired anomalies in the urogenital system, urogenital tract infections, conditions raising scrotal temperature (such as varicocele), endocrine irregularities, genetic variations, immunological aspects, and lifestyle choices. Interestingly, in 30–40% of instances, the cause of male infertility remains unidentified, termed idiopathic male infertility (Bundhun et al. 2019). Nevertheless, semen analysis may uncover irregularities in the spermogram. Various lifestyle elements, including occupational, environmental, and behavioral factors such as tobacco use and alcohol consumption, have been recognized as potential contributors to male infertility.(Meri et al. 2013)

We found that conventional semen parameters were adversely affected by tobacco smoking. Smokers had a significantly higher prevalence of oligozoospermia, teratozoospermia, and asthenozoospermia than non-smokers. This is consistent with the study by Anane et al. (2016), who reported that the proportions of oligozoospermia (27.8% vs 11.1%, p = 0.00047) and teratozoospermia (76.0% vs 39.8%, p = 0.0010) were higher in smokers than non-smokers. Tobacco smoking also impaired sperm motility (asthenozoospermia) and we observed a significant difference between the two groups. A previous meta-analysis by Bundhun et al. (2019) showed a similar effect of tobacco smoking on oligozoospermia (RR: 1.29, 95% CI: 1.05–1.59; p = 0.02), but not on teratozoospermia (RR: 1.22, 95% CI: 0.96–1.56; P = 0.10) or asthenozoospermia (RR: 1.42, 95% CI: 0.97–2.09; p = 0.07).

Smoking can affect the morphology of spermatozoa, causing defects in the head, neck, and tail regions. In this study, smokers had significantly higher head defects with a mean difference of 2.66 [0.57, 4.74], neck defects with a mean difference of 1.95 [0.46, 3.45], and tail defects with a mean difference of 1.30 [0.28, 2.32] than non-smokers. Bundhun et al. (2019) also found significant increases there is a significant difference of 2.44 (with a 95% confidence interval between 0.99 and 3.89) when comparing smokers to non-smokers. This difference is observed in various aspects of sperm morphology, including the head (with a mean difference of 1.76 and a 95% confidence interval between 0.32 and 3.20, with a significance level of p = 0.02), the neck (with a mean difference of 1.97 and a 95% confidence interval between 0.75 and 3.18, with a significance level of p = 0.002), and the tail (with a mean difference of 1.29 and a 95% confidence interval between 0.35 and 2.22, with a significance level of p = 0.007), when comparing smokers and non-smokers.(Bundhun et al. 2019) The association between smoking and sex-hormone-binding globulin was not independent, as Wang et al. demonstrated, and the number of cigarette packets correlated with sex-hormone binding globulin. A Taiwanese study also found no significant difference in LH and FSH levels among smokers and non-smokers (Bundhun et al. 2019).

How smoking affects semen parameters is not fully elucidated, but cigarette-derived chemical compounds have detrimental effects on the maturation of male germ cells, Leydig cells, and Sertoli cells. Nicotine adversely affected sperm morphology and sperm count, and seminal cotinine impaired sperm motility (Sharma et al. 2016). The reduced sperm volume observed in heavy smokers could be attributed to the disruption of the hypothalamus–pituitary–gonadal axis due to heightened nicotine levels and other harmful substances present in cigarettes, or potentially due to an escalated apoptotic process during spermatogenesis. Although the precise mechanisms underlying the detrimental effects of smoking on semen parameters remain partially elusive, a plausible explanation lies in the direct toxic influence of accumulated nicotine (or other chemical constituents) on the epithelium of the male germ line. (Harlev et al. 2015) Cigarette smoke can mutate and damage cells, and some of its components can interfere with the function of male and female gametes prominent constituents like lead, cadmium, nicotine, and benzopyrene have a significant impact on semen characteristics and sperm functionality. This research has noted a correlation between smoking and diminished sperm concentration and motility. (Mitra et al. 2012 and Sharma et al. 2016) In Fig. 2, potential mechanisms by which smoking influences sperm parameters and overall quality are illustrated. Nicotine predominantly exerts detrimental impacts on male reproductive function by promoting the overproduction of reactive oxygen species (ROS). Smoking leads to irreversible DNA damage in sperm. Additionally, elevated levels of active caspases have been identified within spermatozoa of men experiencing infertility, suggesting that an intensified apoptotic process in spermatozoa contributes to diminished semen motility and an increased proportion of deteriorated spermatozoa post-ejaculation (Komiya et al. 2014). The oxidative effects of nicotine on spermatogenesis damages the membrane structure of the sperm cells, causing reduced motility of sperm. Another possible mechanism is the interference of nicotine with the nicotinic acetylcholine receptor of sperm cells, which affects the intracellular Ca+2 dynamics and reduces motility (Mitra et al. 2012 and Harlev et al. 2015). Smoking may also impair motility by altering the expression of eight nAChR subunits and different proteins (Aldoa, ATP5a1, Gpx4, Cs) in human sperm cells, causing smoking-related sperm damage. Moreover, smoking may decrease the activity of Ca2+ ATPase in sperm cells, which is involved in motility regulation. Creatine kinase is an enzyme that provides energy for cells with high energy demand, such as sperm cells. It participates in the metabolism of adenosine triphosphate (ATP) and adenosine diphosphate. Ghaffari and Rostami et al. found that smoking reduced creatine kinase activity in sperm cells, which affected sperm motility and fertility (Harlev et al. 2015).

Smokers had low-quality sperm shape in the study. Heavy metals in cigarettes lead to high levels of oxidative stress. This can damage the membrane and cause shape defects. Heavy metals can also harm DNA during sperm formation, which can affect the normal development of sperm structure. Previous studies found that DNA damage was higher in regular smokers. Previous studies also have shown that heavy metals can cause DNA damage and prevent DNA repair. When DNA is damaged, the Chk1 is activated and stops or delays the cell cycle at S and G2 phases, and it may help the cells survive when agents damage DNA. The Chk1 activates other molecules to start a cellular response that involves changing gene expression, energy use, cell cycle or DNA repair, or killing the cell if the damage is too much to fix (Mitra et al. 2012; Harlev et al. 2015; Cui et al. 2016).

One of the sources of reactive oxygen species (ROS) such as hydroxyl radical (HO), superoxide radical (O₂), or hydrogen peroxide (H₂O₂) is cigarette smoke, which contains heavy metals like lead and cadmium. When the ROS levels surpass the antioxidant capacity of the cells, oxidative stress occurs (18). The sperm membrane and the sperm DNA are susceptible to oxidative stress damage. The seminal plasma may have low antioxidant levels or high oxidant levels from the smoke, resulting in oxidative stress. Additionally, smoking may cause inflammation in the male genital tract, which can generate more ROS from leukocytes. (Harlev et al. 2015)

A positive association between tobacco smoking and seminal OS markers has been demonstrated, as evidenced by a significant rise in ROS levels and reduced ROS-TAC values. Spermatozoa are especially vulnerable to excessive ROS-induced damage due to the high amount of polyunsaturated fatty acids in the plasma membrane that are targets for ROS and the low amounts of scavenging enzymes in their cytoplasm. The sources of heightened levels of reactive oxygen species (ROS) in the seminal fluid of smokers can originate from either internal or external sources. External factors like smoking, alcohol consumption, and exposure to air pollutants represent the external origins of ROS, while the primary internal sources of ROS are white blood cells, specifically neutrophils and macrophages, along with contributions from immature spermatozoa (Harlev et al. 2015).

This study also investigates FSH, LH, and testosterone levels in patients with infertility due to tobacco smoking. The result shows that the testosterone level lower in smokers than non-smokers, while the FSH and LH levels are higher in smokers than non-smokers, albeit insignificantly. Bundhun et al. (1) reported no significant differences in the levels of testosterone (MD: 0.18, 95% CI: -1.26 – 1.63; P = 0.80), LH (MD: 0.18, 95% CI: -0.47 – 0.83; P = 0.58), or FSH (MD: 0.12, 95% CI: -0.41 – 0.64; P = 0.66) among smokers and non-smokers. This contrasts with the study conducted by Mitra et al. (2012). The study revealed that FSH, LH, and testosterone levels were higher, lower, and lower respectively with increased smoking. This conflicts with earlier research that identified positive links between smoking and testosterone and LH levels, along with elevated LH/free testosterone ratios associated with heightened smoking or increased smoking and testosterone. Nicotine, a toxic substance in cigarette smoke, may be responsible for the reduced testosterone in heavy smokers by impairing androgen production and Leydig-cell development. Primary testicular failure, a condition where the testes’ seminiferous tubules are damaged and cannot produce sperm normally, is usually indicated by a high FSH level (Mitra et al. 2012 and Harlev et al. 2015).

Some articles in this study investigate infertility with the total number of cigarettes smoked daily and the number of years of smoking. The study conducted by Cui et al. (2016) showed that progressive motility of the sperm is significantly decreased in moderate and heavy smokers than non-smokers. No association was found between male infertility and the duration or chronicity of smoking in other investigations (Bundhun et al. 2019).

Our study also found the complexity in alcohol’s impact on sperm. Anifandis et al. (2014) identified a positive association between alcohol intake and sperm abnormalities, emphasizing the importance of moderation when it comes to alcohol consumption. Komiya et al. (2014) research delved into the detrimental effects of chronic alcohol use on sperm DNA fragmentation. Their results demonstrated that continuous alcohol consumption could increase Sperm DNA Fragmentation Index (SDFI), contributing to compromised semen quality. This highlights the need for individuals, particularly those of reproductive age, to be aware of the potential consequences of heavy alcohol consumption on their fertility. These findings are in line with the study conducted by Joo et al. (Joo et al. 2012), which found that individuals with high alcohol consumption had fewer morphologically normal sperm cells than those with moderate alcohol consumption. Moderate and high alcohol consumption were associated with fewer normally shaped nuclei compared to very low alcohol consumption. Furthermore, the low alcohol consumption group had fewer sperm cells with normal plasma membranes than the very low alcohol group (p < 0.05). On the other hand, Keskin et al. (2016) found no substantial differences in semen parameters among groups with varying alcohol consumption levels when compared to a control group of non-drinkers. This suggests that moderate alcohol use may not have a significant impact on semen quality, although it’s crucial to remember that individual factors can vary. Additionally, it has been observed to cause damage to sperm morphology, particularly in the sperm head. Hence, it can be observed that there exists a positive correlation between the amount of alcohol use and the decline in sperm quality. The impact of both moderate and heavy smoking on spermmotility is evident, leading to a decline in sperm quality (Amor et al. 2022).

While reversible changes in morphology may occur, heavy alcohol use is associated with decreased sperm volume and concentration. (Boeri et al. 2019) Even short-term alcohol consumption can impact semen quality due to the hormonal imbalance affecting the reproductive axis. Some studies found no impact on sperm parameters, but chronic alcohol consumption may increase DNA fragmentation and apoptosis. Apart from differences in sperm volume (between moderate and non-alcohol consumers) and the percentage of small halos (between heavy and moderate alcohol consumers), no other significant distinctions were identified among the groups. Variations in sperm volume could relate to hypo-testosteronemia in heavy alcohol users. Elevated alcohol consumption may promote apoptosis during spermatogenesis.(Anifandis et al. 2014; Keskin et al. 2016; Joo et al. 2012).

Combining smoking and alcohol amplifies their negative impact on sperm parameters. Despite separate actions, substantial DNA fragmentation differences were seen. Reduced semen volume in combined users points to synergistic impact. The mechanisms remain unclear, but the study by Anifandis et al.(2014) suggests that alcohol may hinder the reproductive axis, impacting LH and FSH secretion, while smoking may trigger apoptosis. These results align with Martini et al.’s observations, indicating that dual exposure of tobacco smoking and alcohol consumption impairs sperm quality, especially the sperm’s volume and concentration. (Martini et al. 2004). We believe our study would be very beneficial for the importance of other proffesional practices and education purposes as it clearly highlight the relevances of smoking and alcohol consumption in the impact of sperm quality.

On average, smoking has a detrimental impact on conventional semen characteristics. Increased risk of oligozoospermia, teratozoospermia, asthenozoospermia, and sperm morphological defects were all linked to tobacco use. Alcohol consumption may harm the sperm’s quality. Combining smoking and alcohol amplifies their negative impact on sperm parameters. Due to the harmful effects of both factors, men seeking reproduction should be advised to avoid these habits.