Smoking and Male infertility:

Fact or Fiction

By

Dr. Taymour Mostafa

Prof. Andrology & STDs

Cairo University

History of Tobacco Smoke :

Tobacco plant was named Nicotina tabacum in the honor of Jean Nicot, the French ambassador to Portugal who brought it back with him as a medicine in 1560. Tobacco belongs to the nightshade family, genus Nicotine. The most two common species are Nicotina Tabacum, which is milder and more aromatic and Nicotina Rustica, which is stronger.

Later in 1800, tobacco was used for smoking and distributed by Spanish sailors who carried it with them, wherever they went and planted its seeds in a variety of places around the world leading to its popularity on a worldwide basis.

The way, in which tobacco has been used varied, starting with pipe smoking, snuff taking and then in the form of cigarettes. Tobacco has also been chewed in some countries.

Smoking Behavior :

There is strong evidence that starting smoking is related to social factors, particularly the influence of parents and peer groups. Smoking is a mean of taking substance that excites sensory organs in the lips, mouth and throat, which provide sensations of touch, taste and irritation. Freud argued that smoking and drinking are primitive autoerotic activities in which there is a constitutional intensification of the erotogenic significance of the labial region.

Smoking Index :

Smoking index (SI) of a smoker is the product of multiplying the number of cigarettes smoked per day by the numbers of smoking. It is categorized into ; mild smoker < 200 SI , moderate smoker 200 - 600 SI and heavy smoker > 600 SI.

Composition of Cigarette Smoke :

Cigarette smoke consists of gases, vaporized liquids and particles, many of which are in minute droplets. About 4000 compounds are generated by a lighted cigarette through many processes such as hydrogenation, pyrolysis, oxidation, decarboxylation , dehydration,...etc. Smoke is separated into two phases; gaseous phase and particulate phase. Aldhydes, ketones, organic acid and alcohol are found in the particulate phase. The gas phase consists mainly of nitrogen, oxygen, carbon monoxide and carbon dioxide with traces of nitrogen oxide, ammonia, cyanides. The tar contains all the particulate phase of the smoke as well as the condensable part of the gas phase. The amount of tar from the smoke of one cigarette is between 3-40 mg depending on the burning and condensing conditions, the length of the cigarette, the use of a filter, porosity of paper, the content of tobacco, its weight and kind.

Collectively, the major constituents which severely cause health hazards of the smokers are: i- Nicotine and Tar in the particulate phase.

ii- Carbon monoxide in the gas phase.

Main-stream and Side-stream Smoke :

Main-stream smoke emerges into environment after it is drawn through the cigarette, filtered by smoker's own lungs, and then exhaled outside. Side-stream smoke arises from the burning end of the cigarette and enters directly into the environment. Many potentially toxic gas phase constituents are in higher concentration in side-stream smoke than in main-stream smoke and nearly 85% of smoke in a room results from side-stream smoke. Side-stream smoke is generally diluted in a considerably larger volume of air. Thus, passive smokers are exposed to a quantitatively smaller and potentially qualitatively different smoke exposure than active smokers.

Passive Smoking

Passive smoking refers to the involuntary inhalation of tobacco smoke present in the air that people breath. A short-term increase in blood pressure was reported in passive smokers with acute exposure to cigarette smoke . Increase in carboxyhaemoglobin level , functional residual capacity, residual volume, heart rate together with eye irritation, nasal discharge and cough were also reported.

Smoking and Male Infertility

Health or smoking is a well-known statement facing smoking, because of its confirmed hazardous effect on health. The risks associated with tobacco smoking appeared to be closely related to the amount of smoke inhaled as well as the constituents of the cigarettes. It is confirmed that smokers are at risk for cardiovascular diseases , lung disorders , complications of pregnancy , gastrointestinal complications , osteoporosis and altered drug metabolism.

However, despite the number of papers which have been published, there is still no clear understanding of the extent to which smoking in general, and various components of cigarette smoke in particular, exert a detrimental effect on the male reproductive potential.

On the other hand, several reports denied a deleterious relation between smoking and male fertility potential on semen parameters putting into consideration that much of fertile males are smokers.

However, it is demonstrated by different scientific papers that smoking has a deleterious effect on male infertility potential through multiple ways. These can be summarized in the following points:

1. Semen picture:

Indeed , cigarette smoking in males has been implicated as a cause of decreased sperm numbers and an increased frequency of abnormal sperm morphology as well as a decrease in sexual performance.

The effect of smoking on conventional semen parameters in men of reproductive age showed that semen volume was smaller in heavy smokers than in non-smokers.

There existed a trend of increase of percentage of men with deviations in motility and morphology with the increase of the cigarettes smoked per day. The rapid decrease in the survival spermatozoa in smokers may be harmful in respect of fertility.

Findings showed that smokers had lower percentages of morphologically normal spermatozoa, poorer morphometric parameters.

In comparison with those who have never smoked, current smokers were at increased risk of dyspermia versus both normozoospermic men of infertile couples and fertile men of unknown semen quality, and the risk increased with number of cigarette smoked per day and duration of smoking. It was shown that the risk of dyspermia increased with number of cups of coffee per day compared with men drinking no or one cup/day.

Also, smokers also demonstrated detached ciliary tufts in semen. It is postulated that these tufts originated from the epididymal epithelium and shed as a part of epididymal involvement , which occurs as a result of testicular pathology caused by several noxious agents.

2. Smoking and Sperm Function Tests

Different sperm function tests demonstrated significant poorer function in smokers versus non-smokers. It was concluded that sperm-fertilizing potential is reduced in men who smoke, possibly because of alterations in the sperm cytoskeleton during either spermatogenesis or sperm maturation in the epididymis. The primary defect may be deficient secretory function of the Leydig and/or Sertoli cells.

3. Smoking and Chromosomal Damage

The hypothesis of diminished fertilizing capacity in smokers is supported also at the chromosomal level. A significantly higher ratio of single-stranded-to-double-stranded DNA spermatozoa was found in smokers. Single stranded DNA spermatozoa have lower fertilizing capacity than do double-stranded DNA spermatozoa.

Therefore , smokers should stop smoking not only in respect to their own health but as a sense of responsibility for the future generations too.

The reason for this conclusion is that tobacco smoke contains numerous mutagenic substances reaching the male gonads via the blood.

4. Effect of Acrosin

Smokers exhibited lower acrosin activity in presence of normal sperm count and motility. The inducibility of the acrosome reaction was significantly lower in semen samples from smokers than fertile group.

5. Smoking and Toxic Materials in Semen

Data indicated that exposure to environmental tobacco smoke resulted in measurable nicotine and cotinine (end product of nicotine) levels in seminal plasma. Seminal plasma cotinine concentration either in active or passive smokers showed a significant positive correlation with degree of reported exposure. Also, seminal plasma cadmium in smokers was elevated with a significant difference to non-smokers if more than 20 cigarettes were consumed daily. The high level of cadmium found in smokers with asthenospermia is an evidence of the toxic effect of this trace element to cause asthenospermia.

6. Smoking and Hormones

Different evidences suggested that nicotine could alter the hypothalamic-pituitary axis through its stimulation of growth hormone, cortisol, vasopressin and oxytocin release, which in turn inhibit luteinizing hormone (LH) and prolactin release. The mean estradiol level was higher in smokers than non-smokers, whereas the levels of testosterone and dehydroepiandrosterone are similar and did not differ significantly in smokers compared to non-smokers. Smokers have also lower mean levels of LH, FSH and prolactin than non-smokers. In addition, smokers had significantly lower testosterone levels in the left testicular vein than non-smoking men, and lower in vitro androgen-binding protein secretion rates.

7. Smoking and Varicocele

The combination of smoking and testicular varicocele was strongly related to the incidence of oligozoospermia. Smokers with testicular varicocele had a disproportionately higher incidence of oligozoospermia. Smokers with testicular varicocele had an incidence of oligozoospermia 10 times greater than in non-smokers with testicular varicocele and 5 times greater than in smokers without testicular varicocele. The pathophysiologic basis of the interaction between smoking and varicocele was theorized to be due to an increased secretion of catecholamine from the adrenal medulla, induced by cigarette smoking. The elevated catecholamine in the renal vein would then reach the testes via retrograde flow down the internal spermatic vein in men with testicular varicocele resulting in seminiferous tubular damage.

8. Smoking and Antioxidants in semen

The fact that human spermatozoa can generate reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide is documented. The mechanism for superoxide anion production appears to be via an NADPH⁺ oxidase located in the sperm plasma membrane. The biological significance of this highly specialized and potentially precious free radical generating system is currently known and its role in the etiology of defective sperm function appears to be significant.

The pathological significance of ROS production by human sperms stems from its considerable capacity to exhibit this activity especially abnormal forms which increased in smoker’s semen. The clinical significance of this variability rests in the inverse relation between it and the integrity of human sperm function. Combination of antioxidants present in seminal plasma including superoxide dismutase, vitamin C, selenium, transferrin, glutathione peroxidase, albumin and uric acid would protect the sperm by their concentration in normal condition, and when present in balanced formulation.

Ascorbic acid (vit.C) is the most essential factor of these antioxidants in semen. The human seminal plasma contains ascorbic acid more than nine times its concentration in human blood plasma. Seminal plasma ascorbic acid level is demonstrated to decreas in smokers versus non-smokers pointing to the hazardous effect of smoking since the addition of reactive oxidants from exogenous sources to the semen exerted a matching requirement for increased ascorbic acid.

Therefore, several reports had indicated that heavy smoking in men (20 cigarettes/day) is associated with 20% to 40% decrease in serum ascorbic acid levels as well as increased sperm abnormalities. Hence, it is suggested to supplement ascorbic acid tablets to heavy smokers with demonstration of improvement regarding sperm quality.

Finally, because of the large number of men worldwide who smoke the fact that cigarette smoke contains known mutagens and carcinogens, there has been concern that smoking may have adverse effects on male reproduction. A review of the epidemiological literature indicated that cigarette smoking is associated with modest reductions in semen quality including sperm concentration, motility and morphology. Smoking has also been associated with alterations in hormone levels in males. However, despite modest reduction in semen quality and altered hormone levels among smokers compared to non-smokers, studies have not shown a reduction in male fertility in association with paternal smoking. Also, smoking has not been shown to be mutagenic to human spermatozoa.

It is concluded that, men with marginal semen quality , infertile men with varicocele and those with asthenospermic semen who wish to have children may benefit from quitting smoking, since several studies indicating the potential for improved semen quality after quitting smoking.

Therefore, Please Quit Smoking ,,,