Effect of cigarette smoking on serum testosterone level among male smokers: a cross-sectional study
Mohamed A.A El Salam1, Shady Zaki1, Mohamed S Mousa2, Ahmed Motawi1
1 Department of Andrology, Sexology and STDs, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Pulmonary Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
Correspondence Address:
MD Mohamed S Mousa
Department of Pulmonary Medicine, Faculty of Medicine, Cairo University, Cairo 11421
Egypt
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ejcdt.ejcdt_61_20
Objective Smoking is considered as a growing epidemic worldwide, and it was found to have negative influence on health, causing a variety of diseases in both sexes, such as pulmonary fibrosis, chronic obstructive pulmonary disease, cerebrovascular and cardiovascular disorders, pulmonary and extrapulmonary malignancies, infertility, erectile dysfunction, recurrent abortions, and teratogenicity. In addition, several studies have been conducted owing to concerns on its effect on the endocrinal system in males, especially its effects on testosterone levels; however, this concern is still debatable, and all reported results were conflicting.
Patients and methods Herein, the cohort study was conducted on a subgroup of smoking males (n=155) to evaluate its effect on serum total testosterone (T), estradiol (E2), as well as T/E2 ratio compared with a non-smoking control group (n=134).
Results Our results have shown that there was a significant statistical difference between smoker and non-smoker groups concerning serum total testosterone (T), estradiol (E2), and subsequently T/E2 ratio, with P values of 0.002, less than 0.001, and less than 0.001, respectively. In addition, there was a statistically significant negative correlation between the duration of smoking and T. However, there was no correlation between duration of smoking and either E2 or T/E2 ratio.
Conclusion Thus, the current study added further evidence to the unsettled debate suggesting negative harmful effects of smoking on serum testosterone level.
Keywords: cigarette smoking, estradiol, hormones, hypogonadism, testosterone
Smoking is a globally prevailing epidemic that is responsible for a variety of both non-communicable health hazards and mortalities. According to the WHO statistics, each year ∼4 million deaths are due to smoking-related diseases [1],[2]. It is estimated that there is approximately one billion tobacco smokers worldwide, being more prevalent among males than female [3]. In addition, tobacco smoking is consumed in different forms, including cigarettes, cigar, e-cigarettes, and water-pipe [4].
Regardless of the pattern of smoking, it was found that more than 7000 toxic chemicals were produced from tobacco, whereas ∼70 of them are potentially carcinogenic [5],[6].
Several health hazards had been related to smoking, which include chronic bronchitis, bronchial asthma, emphysema, ischemic heart diseases, stroke, peripheral vascular diseases, increased incidence of various cancers, and osteoporosis [7],[8].
Besides that, smoking has been mentioned as a negative influencer of embryogenesis, as it may cause recurrent abortions, intrauterine growth retardation, fetal distress, preterm labor, low-birth weight, as well as potential teratogenicity [9],[10].
In other perspective, cigarette smoking has been found to negatively influence the endocrinal system, causing pituitary, thyroid, adrenal, testicular, and ovarian dysfunctions [11]. Specifically, there were a lot of unsettled debates concerning the potential effects of smoking on male sex hormones, especially testosterone levels. Notably, some clinical trials have demonstrated evidence suggesting no significant difference in testosterone levels (between smoker and nonsmokers) or association between tobacco smoking and testosterone levels [12]. On the contrary, others have demonstrated significant difference and association between smoking and testosterone on comparing smokers compared with nonsmokers, where some reported higher levels of testosterone [13],[14],[15], whereas others reported lower levels [16],[17],[18]. Therefore, the aim of this study was to evaluate the effect of cigarette smoking on levels of serum testosterone (T), estradiol (E2), as well as T/E2 ratio among smokers and nonsmokers.
Patients and methodsThis cross-sectional study enrolled 289 participants. All participants were recruited from Kasr Al-Ainy outpatient clinics during the period from June to December 2019. They were divided into two groups: a case group of smokers (n=155) and a control group of apparently healthy nonsmokers (n=134). Both groups were matched for age, which ranged from 20 to 40 years as, well as BMI less than 25.
The selected participants were subjected to certain exclusion criteria that could affect hormone levels, including being an elderly male, those who have partial androgen-deficiency symptoms, those with testicular atrophy or small sized testes, those with hepatic or renal dysfunction, patients receiving hormonal therapy, alcohol intake patients, those with addiction, or those using recreational drugs.
All included participants have been subjected to full medical history taking and clinical examination (general and local). It is to be mentioned that the smoker group was referred to pulmonary medicine outpatient clinic for full pulmonary assessment to exclude any preexisting chronic lung diseases. Their assessment included history taking and clinical assessment for any chest complaint, smoking history and calculation of smoking index (SI), chest radiography, spirometry to exclude obstructive lung disease due to smoking, and measurement of oxygen saturation by pulse oximetry.
Moreover, 3 ml of a venous blood sample was collected from each participant between 8:00 and 11 a.m. for measuring serum levels of total testosterone and estradiol. Hormonal levels were measured using an electro-chemiluminescence immunoassay analyzer (Roche Co., Cobas e 602, Japan). The normal reference values were as follow: testosterone (total)=2.5–8.4 ng/ml, estradiol (E2) less than 40 pg/ml, as well as estimated T/E2 ratio greater than or equal to 10.
In addition, smokers were stratified according to the pattern of smoking into mild, moderate, and heavy smokers using the SI. Notably, the SI was calculated using the number of cigarettes smoked daily multiplied by the years of smoking. We considered mild smoking when SI ranged between 0 and less than or equal to 200, whereas moderate smokers whose SI is greater than 200 and less than or equal to 400, and heavy smokers whose SI was more than 400 [19]. Furthermore, approval of the Local Ethical Committee was obtained to conduct the current study. Besides that, a written informed consent from all participants about the purpose of the study that conforms to Helsinki declaration (1964) was collected.
By the end of the study, all collected data were coded and entered using the statistical package SPSS V.25 (statistical package for the social sciences version 25), IBM SPSS Statistics, USA. Data were summarized using mean, SD, median, minimum and maximum for quantitative variables and frequencies (number of cases) and relative frequencies (percentages) for categorical variables. Comparisons between groups were done using unpaired t-test when comparing two groups and analysis of variance with multiple comparisons post-hoc test when comparing more than two groups [20]. Correlations between quantitative variables were done using Pearson correlation coefficient [21]. P values less than 0.05 were considered as statistically significant.
ResultsThe current study included 289 participants who were recruited from Kasr Al-Ainy outpatient clinics at the Faculty of Medicine, Cairo University, during a 6-month interval from June to December 2019. They were divided into two groups that were age matched (20–40 years) as follows: cases (n=155) who were smokers and control group (n=134) who were nonsmokers. According to the pattern of smoking, the case group included mild (n=49, 31.6%), moderate (n=39, 25.2%), and heavy (n=67, 43.2%) smokers, with a mean duration of smoking of 11.46±5.40 years.
Both groups were evaluated for serum levels of testosterone (T), estradiol (E2) and estimated testosterone to estradiol ratio (T/E2), as shown in [Table 1]. Our results showed statistically significant difference concerning serum testosterone level, being lower among smokers, with mean testosterone of 4.09±2.04 ng/ml, compared with nonsmokers, with mean testosterone of 5.61±5.62, with P value 0.002. In addition, the serum estradiol level was found to be significantly higher among smokers compared with nonsmokers, with mean levels of 49.18±18.84 and 35.97±12.39 pg/ml, respectively, with P value less than 0.001. Subsequently, there was a high statistically significant difference in estimated T/E2 ratio, being lower among smokers compared with nonsmokers, with mean levels of 8.11±3.32 and 14.69±6.18, respectively, with P value less than 0.001.
Table 1 The mean levels of serum total testosterone (T), estradiol (E2), and T/E2 ratio among smokers and nonsmokersOn the contrary, results showed a statistically significant negative correlation between duration of smoking and serum T level, with P value 0.036 and correlation coefficient of −0.169. However, there was no significant correlation between duration of smoking with either E2 or T/E2 ratio, with P values of 0.970 and 0.182, respectively ([Table 2]).
DiscussionSmoking is considered as a globally rising epidemic all over the world, affecting both developed as well as developing countries, and has been related to many health hazards that include a lot of non-communicable diseases. In addition, smoking has been found to have a negative influence on various endocrine glands, including the gonadal function that may predispose to hypogonadism [11].
However, up till now, there are a lot of conflicting results concerning the effect of smoking on testosterone levels as evident in animal and human studies. Therefore, the current study was aiming at evaluating the effect of smoking on serum level of testosterone, E2, as well as T/E2 ratio among smokers and nonsmokers.
Our results showed that serum testosterone levels among smokers were significantly lower compared with nonsmokers. This agrees with a previous research work conducted by Shaarawy and Mahmoud [16], who had evaluated the endocrinal status as well as semen parameters among smokers. Their results demonstrated significant decrease in total testosterone levels in serum among smokers compared to non-smokers. Similarly but not identically, Olayaki et al. [17] have conducted a study regarding the effect of cigarette smoking on urinary testosterone levels, and they found a reduced concentration of urinary testosterone in male smokers compared to nonsmokers. Finally, Abdrabo [18] conducted a study that was aimed at assessing the effect of cigarette smoking on leutinizing hormone (LH), prolactin, and testosterone hormones among Sudanese males. Their results have demonstrated a significant decrease of serum testosterone level among smokers compared with nonsmokers; however, there was no significant difference concerning LH and prolactin levels among both groups.
Several theories have been hypothesized regarding the mechanisms by which smoking lowers testosterone levels owing to Leydig cell dysfunction by various mechanisms such as chronic hypoxia, smoke-induced oxidative stress (ROS), neuroendocrinal effect of nicotine on hypothalamo-pituitary-gonadal axis, direct cytotoxic effect on Leydig cells either causing downregulation of key enzymes of steroidogenesis (NR5A1, CYP11A1, and 3b-HSD1) or by inducing apoptosis (by increase in Bax (proapoptotic protein) and caspase-3 expression, and a decrease in Bcl-2 (an antiapoptotic protein) expression [22],[23],[24].
On the contrary, other studies evaluating the effect of smoking on serum testosterone levels have found higher levels among smokers. Notably, most of these studies have included the evaluation of testosterone (total and free) as well as sex hormone-binding globulin (SHBG), whereas their results have reported that both (free and total) testosterone as well as SHBG levels were increased among smokers compared with nonsmokers [25].
Interestingly, English et al. [13] have suggested that the higher levels of total testosterone among smokers could be attributed to SHBG increase. In addition, SHBG levels were correlated with the serum nicotine level. Moreover, a study conducted by Svartberg and Jorde [14] has found a positive association between testosterone levels and smoking even when adjusted to SHBG levels values.
In the same context, Wu et al. [15] have conducted a study to evaluate the effect of several variables, including age, obesity, comorbidity, as well as smoking on reproductive hormones in elderly males. They have found that smoking was associated with higher SHBG, LH, and total testosterone but not free testosterone. These findings were related to the increase in SHBG with a compensatory rise in LH.
Although these studies have found increased testosterone levels among smokers, but the mechanism by which smoking increases testosterone levels remains unclear. However, this increase in testosterone levels could be related to increase levels of SHBG in smokers. Besides that, nicotine-mediated inhibition of aromatase activity with subsequent increase in testosterone levels has also been suggested [25],[26].
This study adds to the previously conducted research studies evaluating the influence of smoking on testosterone levels, whereas it showed significant decline in serum testosterone levels. In the same context, it showed elevation in serum estradiol levels with subsequent disturbance of T/E2 ratio among smokers compared with nonsmokers. Moreover, further studies are needed to be conducted deploying larger cohorts to figure out this potential association.
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Conflicts of interest
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