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ORIGINAL ARTICLE
Lifestyle causes of male infertility
Damayanthi Durairajanayagam
*
Discipline of Physiology, Faculty of Medicine, Sungai Buloh Campus, Universiti Teknologi MARA, Selangor, Malaysia
Received 12 November 2017, Received in revised form 5 December 2017, Accepted 12 December 2017
KEYWORDS
Male infertility;
Lifestyle;
Risk factors;
Semen quality;
Sperm DNA fragmen-
tation
ABBREVIATIONS
AAS, anabolic–
androgenic steroids;
APA, advanced pater-
nal age;
ASIH, anabolic
steroid-induced
hypogonadism;
ART, assisted
reproductive technol-
ogy;
BMI, body mass index;
Chk1, checkpoint
kinase 1;
Abstract Objective: To examine the potential effects of lifestyle factors on male
reproductive health. Evidence of a global decline in human sperm quality over recent
decades has been accumulating. Environmental, occupational, and modifiable life-
style factors may contribute to this decline. This review focuses on key lifestyle fac-
tors that are associated with male infertility such as smoking cigarettes, alcohol
intake, use of illicit drugs, obesity, psychological stress, advanced paternal age, diet-
ary practices, and coffee consumption. Other factors such as testicular heat stress,
intense cycling training, lack of sleep and exposure to electromagnetic radiation
from mobile phone use are briefly discussed.
Materials and method: A comprehensive literature search was performed to iden-
tify and synthesise all relevant information, mainly from within the last decade, on
the major lifestyle factors associated with male infertility and semen quality. Data-
base searches were limited to reports published in English only. A manual search of
bibliographies of the reports retrieved was conducted to identify additional relevant
articles.
Results: In all, 1012 articles were identified from the database search and after
reviewing the titles and abstract of the reports, 104 articles met the inclusion criteria.
Of these, 30 reports were excluded as the full-text could not be retrieved and the
abstract did not have relevant data. The remaining 74 reports were reviewed for data
on association between a particular lifestyle factor and male infertility and were
included in the present review.
Conclusion: The major lifestyle factors discussed in the present review are
amongst the multiple potential risk factors that could impair male fertility. However,
*Address: Discipline of Physiology, Faculty of Medicine, Sungai Buloh Campus, Universiti Teknologi MARA, Jalan Hospital, 47000 Sungai
Buloh, Selangor, Malaysia. Fax: +60 3 6126 5224.
E-mail addresses: damayanthi@salam.uitm.edu.my,damayanthi.d@gmail.com.
Peer review under responsibility of Arab Association of Urology.
Production and hosting by Elsevier
Arab Journal of Urology (2018) xxx, xxx–xxx
Arab Journal of Urology
(Official Journal of the Arab Association of Urology)
www.sciencedirect.com
https://doi.org/10.1016/j.aju.2017.12.004
2090-598X Ó2018 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Ar ab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
ECS, endogenous can-
nabinoid system;
GnIH, gonadotropin-
inhibitory hormone;
HADS, Hospital
Anxiety and Depres-
sion Score;
HPA, hypothalamus–
pituitary–adrenal;
HPG, hypothalamus–
pituitary–gonadal;
IVF, in vitro fertilisa-
tion;
ICSI, intracytoplasmic
sperm injection;
IUI, intrauterine
insemination;
MMP, mitochondrial
membrane potential;
ROS, reactive oxygen
species;
SOD, superoxide
dismutase
their negative impact may well be mostly overcome by behaviour modification and
better lifestyle choices. Greater awareness and recognition of the possible impact of
these lifestyle factors are important amongst couples seeking conception.
Ó2018 Production and hosting by Elsevier B.V. on behalf of Arab Association of
Urology. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
There has been increasing evidence on the global decline
in human sperm quality over the past few decades [1–4].
In the most recent report, Levine’s group performed a
systematic review and meta-regression analysis of the
current trends in sperm counts. The comprehensive
study involved 42 935 men with samples spanning over
40 years. They reported a significant decline of 50–
60% in sperm counts amongst men from North Amer-
ica, Europe, Australia and New Zealand [5]. This latest
finding has sparked even greater concern over the rea-
sons behind the apparent decline in the sperm count of
Western men.
As male fertility can be influenced by a variety of fac-
tors, one possible explanation for the declining trend
would be that there are environmental and/or occupa-
tional factors along with lifestyle practices that con-
tribute to the deterioration of semen quality [6–9].
The present article reviews the available evidence
examining the potential effects of lifestyle factors on
male reproductive health. It focuses on the following
lifestyle factors that are associated with male infertility:
smoking cigarettes, alcohol intake, use of illicit drugs,
obesity, psychological stress, advanced paternal age,
dietary practices, and coffee consumption. Other fac-
tors such as testicular heat stress, intense cycling train-
ing, lack of sleep, and exposure to electromagnetic
radiation from mobile phone use are also briefly
touched upon.
Materials and methods
A systematic review of literature was conducted using
PubMed over the last 10 years (from December 2008
to November 2017) for all published reports on the
major lifestyle factors associated with male infertility
(Fig. 1). The inclusion criterion was English language
studies reporting on the lifestyle factors associated with
male infertility such as ‘smoking’, ‘alcohol’, ‘marijuana’,
‘cocaine’, ‘anabolic steroids’, ‘diet’, ‘obesity’, ‘BMI’,
‘psychological stress, ‘advanced paternal age’, and ‘caf-
feine’. The keyword search terms for each of these fac-
tors were used in combination with the following
search terms: ‘male infertility’, ‘male fertility’, ‘sperm
quality’, ‘semen parameters’, ‘DNA fragmentation’, ‘pa-
ternal’, ‘maternal’, ‘ART’, and ‘IVF’. Pertinent studies
that were published prior to the 10-year timeframe were
included at the discretion of the author, as were some
studies on testicular heat stress, intense cycling training,
lack of sleep, and exposure to electromagnetic radiation
from mobile phone use. Reference lists of the reports
were searched for further relevant citations, which were
subject to the inclusion criteria. All non-English lan-
guage studies and those without a published abstract
were not included.
Results
In all, 1012 articles were identified from the database
search and after reviewing the titles and abstract of the
2 Durairajanayagam
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Arab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
reports, 104 articles met the inclusion criteria. Of these,
30 reports were excluded as the full-text could not be
retrieved and the abstract did not have data on the asso-
ciation between the lifestyle factor of interest and male
infertility. The remaining 74 reports were reviewed for
data on the association between a particular lifestyle fac-
tor and male infertility. Available evidence pertaining to
the potential adverse effects of these lifestyle factors on
male fertility vary in strength. Certain factors, such as
cigarette smoking and alcohol intake are likely to exert
an additive effect, whilst other factors may pose a threat
when exposed along with other environmental and occu-
pational factors.
Smoking
Cigarette smoke contains >7000 chemicals, including
highly carcinogenic tobacco-specific nitrosamines, [e.g.
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-
nitrosonornicotine], polycyclic aromatic hydrocarbons
(e.g. benzo[a]pyrene), and volatile organic compounds
(e.g. benzene) [10]. Cigarette smokers have increased
exposure to hazardous substances such as tar, nicotine
(which is highly addictive), carbon monoxide, and heavy
metals (e.g. cadmium and lead) [11].
Cigarette smoking is a known potential risk factor for
decreased male fertility. Smoking is associated with leu-
cocytospermia, a major endogenous source of reactive
oxygen species (ROS). Moreover, tobacco smoke con-
tains ROS at levels that can overwhelm the endogenous
antioxidant defences. Increased seminal levels of ROS in
smokers expose spermatozoa to oxidative stress, conse-
quently impairing sperm function and ultimately com-
promising male fertility (reviewed in [12]). However,
the mechanisms underlying the effects of smoking on
sperm quality have not been fully clarified.
A large meta-analysis involving males from 26 coun-
tries/regions concluded that smoking causes a decline in
sperm quality in both fertile and infertile men [13].
Sperm concentration in male smokers was reported to
be typically 13–17% lower than that of non-smokers
[14]. Moreover, cigarette smoking has been negatively
associated with sperm count, motility, and morphology.
The decline in semen quality was found to be more
marked in heavy (>20 cigarettes/day) and moderate
(10–20 cigarettes/day) smokers compared to mild smok-
ers (1–10 cigarettes/day). The effect size was higher in
infertile males than in the general population [15].
Besides its association with impaired male fertility,
tobacco smoking is also responsible for increases in
DNA damage, aneuploidies, and mutations in sperm
[16]. One study suggested that the deterioration of
semen quality amongst male smokers was correlated
with increased DNA fragmentation rates and decreased
expression of checkpoint kinase 1 (Chk1). Without the
activation of Chk1 in response to DNA damage, there
would be a decline in sperm repair leading to increased
sperm apoptosis, which could lower semen quality [17].
Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart outlining the process of database
search for study identification, screening, eligibility, and inclusion.
Lifestyle causes of male infertility 3
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Ar ab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
Thus, the general effect of cigarette smoking on male
fertility may result from the combined roles of elevated
oxidative stress, DNA damage, and cell apoptosis,
which could explain not only the reduction in semen
quality, but also impaired spermatogenesis, sperm mat-
uration, and sperm function reported to be present in
smokers compared to non-smokers. Contributing fac-
tors leading to these effects in male smokers include
the presence of nicotine and its metabolite, cotinine,
benzo(a)pyrene, as well as cadmium levels [11]. For
example, a meta-analysis of 13 317 men found that
smoking was associated with higher mean testosterone
levels, which could be attributed to the inhibition of
testosterone breakdown by cotinine [18].
Pre-conception paternal smoking presents an
increased risk of several morbidities in the offspring,
which could perhaps be mediated via epigenetic modifi-
cations transmitted through spermatozoa. Male smok-
ers showed a tendency towards increased alterations in
methylation patterns genome-wide in their sperm
DNA compared with never-smokers [19]. Maternal
smoking during pregnancy and lactation could poten-
tially cause harmful effects on male offspring fertility.
Maternal cigarette smoke exposure during the gestation
and weaning period was shown to cause diminished
germ cell population, germ cell DNA damage, and
defective sperm in the male offspring [20].
With paternal smoking being a significant risk factor
for in vitro fertilisation (IVF) and intracytoplasmic sperm
injection (ICSI) failure, paternal smoking could perhaps
contribute to decreased assisted reproductive technology
(ART) success rates as much as maternal smoking (a risk
factor only for IVF failure) does or more [21]. Moreover,
male smoking could even influence the clinical pregnancy
rate per intrauterine insemination (IUI) cycle [22].
Amongst former smokers, every additional year follow-
ing the male partner’s smoking cessation reduced the risk
of ART failure by 4%, particularly between clinical preg-
nancy and live birth [23].
Despite there being no concrete potential relationship
between smoking and male infertility as of yet, available
evidence on cigarette smoking and male fertility support
the recommendation of smoking cessation and minimis-
ing exposure to tobacco smoke amongst couples who
are trying to conceive.
Alcohol
A meta-analysis involving 29 914 men reported a signif-
icant association between alcohol intake and lower
semen volume, but not sperm parameters [13]. However,
a recent meta-analysis involving 16 395 men reported
that alcohol intake has a detrimental effect on semen
volume and sperm morphology [24]. Direct exposure
of spermatozoa to alcohol (at concentrations corre-
sponding to that of serum after moderate and heavy
drinking) was found to be harmful to sperm motility
and morphology in a dose-dependent manner [25].
The actions of alcohol on the male reproductive sys-
tem seem to occur at all levels of the hypothalamus–pi
tuitary–gonadal (HPG) axis. Alcohol appears to inter-
fere with the production of GnRH, FSH, LH, and
testosterone, as well as impair the functions of Leydig
and Sertoli cells. As a result, the production, morpho-
logical development and maturation of spermatozoa
could be impaired [26]. Spermatogenesis appears to
gradually decline with increasing levels of alcohol intake
[27]. Partial or complete spermatogenic arrest and Ser-
toli cell-only syndrome were more commonly present
amongst heavy drinkers compared to non-drinkers [28].
Chronic alcohol intake was found to have a detri-
mental effect on both semen quality and the levels of
male reproductive hormones [29]. Conversely, a study
comprising 8344 healthy male volunteers found that
moderate alcohol intake was associated with higher
testosterone levels but not with semen quality [30].
Chronic ethanol administration has been shown to
decrease testicular steroidogenic and antioxidant
enzyme activities resulting in increased oxidative stress
[31], which could disrupt testosterone synthesis and
compromise fertility.
A study on the male partners of couples facing pri-
mary infertility found that teratozoospermia was present
in 63% and 72% of males who drank alcohol moder-
ately (40–80 g/day) and heavily (>80 g/day), respec-
tively. None of the heavy alcohol drinkers were
normozoospermic and most were oligozoospermic
(64%), which is suggestive of progressive testicular dam-
age in relation to increasing daily alcohol intake [32].
Similarly, another study found alcohol consumption
rates to be significantly higher in men with severe oligo-
zoospermia and with non-obstructive azoospermia com-
pared to fertile controls [33].
Although the effects of alcohol on male reproductive
function are dependent on the intake amount, a thresh-
old amount of alcohol beyond which the risk of male
infertility increases has not yet been determined. More-
over, it must be kept in mind that whilst alcohol intake
and cigarette smoking alone did not affect sperm param-
eters, both habits together appear to exert an additive
effect that could adversely alter sperm parameters [34].
Recreational drugs
Marijuana, cocaine, anabolic–androgenic steroids
(AAS), opiates (narcotics), and methamphetamines are
examples of illicit drugs that exert a negative impact
on male fertility. The adverse effects of these drugs
could impair the HPG axis, testicular architecture, and
sperm function [35].
Cannabis or commonly referred to as marijuana, is
the most abused illicit drug globally and has
4 Durairajanayagam
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Arab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
predominantly male users. Regular marijuana smoking
(more than once weekly within the last 3 months) was
found to lower sperm concentration and total sperm
count amongst young men, and this effect was further
exacerbated when marijuana was used in combination
with other recreational drugs [36]. Deregulation of the
endogenous cannabinoid system (ECS) was shown to
significantly impair spermatogenesis resulting in lower
total sperm count and motility [37]. Competition
between the phytocannabinoids in marijuana and endo-
cannabinoids for binding to the cannabinoid and vanil-
loid receptors leads to disruption of the homoeostasis of
the ECS, which could consequently impair male fertility
[38]. Sperm from infertile men have a marked modula-
tion of endocannabinoid metabolism and reduction in
endocannabinoid biosynthesis compared to sperm from
fertile men [39].
Cocaine is a highly addictive, strong stimulant drug.
Male rats given high doses of cocaine chronically before
mating had lower pregnancy rates and offspring birth
weights [40]. Both acute and chronic exposure to cocaine
disrupted spermatogenesis and damaged the testicular
ultrastructure [40,41]. These changes could have been
brought about by cocaine-induced apoptosis [42].
Long-term (5 years) cocaine users were associated with
lower sperm concentration and motility, and a higher
fraction of sperm with abnormal morphology [43].
Compared to other infertile men, infertile cocaine users
are more likely to have other concurrent risk factors of
male infertility such as smoking, (other) substance
abuse, as well as a prior history of sexually transmitted
infections [44].
Testosterone and its derivatives comprise a family of
hormones called AAS. AAS are used primarily by males
to enhance their athletic performance and/or personal
appearance [45]. The use of AAS has expanded beyond
that of professional athletes and the prevalence of ana-
bolic steroid-induced hypogonadism (ASIH) amongst
young men and teenagers is on the rise [46]. A retrospec-
tive study found that ASIH was the most common cause
of profound hypogonadism (50 ng/dL testosterone)
amongst men who sought treatment for hypogonadism
[47]. Increased levels of exogenous testosterone, result-
ing from AAS use, exert a negative feedback on the
HPG axis causing reversible suppression of spermatoge-
nesis, testicular atrophy, and infertility. This may result
in transient azoospermia with a recovery period of pos-
sibly even up to 2 years. Additionally, ASIH induced by
AAS abuse can also result in loss of libido and erectile
dysfunction [48]. Consequences from AAS use and sub-
sequently treatment of the resulting hypogonadotrophic
hypogonadism depend on the dose, duration, and type
of AAS used [49]. Some studies have pointed towards
a more permanent repercussion of steroid use on male
fertility and as such, AAS use should be highly discour-
aged [50].
Obesity
Overweight and obesity are associated with excessive fat
accumulation, which can be evaluated using the body
mass index (BMI). Overweight (BMI 25–<30 kg/m
2
)
and obese (BMI 30 kg/m
2
) males are associated with
a decrease in sperm quality and a greater risk of infertil-
ity. A systematic review of 30 studies comprising 115 158
males found that paternal obesity was associated with
lowered male reproductive potential. Men who were
obese had a higher percentage of sperm with DNA frag-
mentation, abnormal morphology, and low mitochon-
drial membrane potential (MMP), and were more
likely to be infertile [51]. Sperm with high DNA frag-
mentation and low MMP are associated with high levels
of ROS [52].
A meta-analysis involving 13 077 men reported that
obese men were more likely to be oligozoospermic or
azoospermic compared to men within a normal weight
range [53]. A population-based study found that as
BMI and waist circumference increased, the prevalence
of low ejaculate volume, sperm concentration, and total
sperm count were also greater in overweight and obese
men of unknown fertility. However, they did not find
an association between body size and sperm motility,
morphology or DNA damage [54]. A smaller study com-
prising 23.3% obese men showed that males who were
overweight and obese had no increased relative risk of
abnormal semen parameters, although their testosterone
and sex hormone-binding globulin levels decreased with
increasing BMI [55]. Additionally, inhibin B levels are
decreased, whilst oestradiol levels are increased in over-
weight or obese men [56].
The presence of excess white adipose tissue in obese
individuals causes increased conversion of testosterone
to oestrogen, and affects the HPG axis leading to a
reduction in gonadotrophin release. These effects result
in secondary hypogonadism and impaired spermatogen-
esis [57]. Increased production of leptin by the white adi-
pose tissue decreases testosterone production.
Adipokines stimulate the production of ROS by leuco-
cytes. Insulin resistance and dyslipidaemia can induce
systemic inflammation, leading to oxidative stress [58].
Increased scrotal adiposity leads to testicular heat stress
and causes oxidative stress. Increased scrotal tempera-
ture along with lack of activity impairs spermatogenesis.
Increased oxidative stress impairs sperm motility, DNA
integrity, and sperm–oocyte interaction [59].
Obese men who attempt ART have reduced rates of
live birth per ART cycle [51]. Increased paternal BMI
is associated with decreased blastocyst development,
pregnancy, and live-birth rates, but not early embryo
development [60].
One pilot study investigated if maternal obesity could
influence the semen quality of her male offspring.
Increasing maternal BMI had a negative relationship
Lifestyle causes of male infertility 5
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with the offspring’s inhibin B levels. Although the study
found a suggestive trend of impaired fertility status in
the offspring of overweight mothers, it was not statisti-
cally significant [61].
The severity of the consequences of obesity on the
hormonal profile, sperm parameters, and DNA damage,
as well as pregnancy outcomes may be varied due to the
presence of other co-morbidities. Weight loss and lower-
ing of BMI have helped improve sperm quality in some,
but not all men [62].
Psychological stress
Stress, in its many forms, may be detrimental to male
reproductive potential. The classical stress response acti-
vates the sympathetic nervous system and involves the
hypothalamus–pituitary–adrenal (HPA) axis [63]. Both
the HPA axis and gonadotrophin-inhibitory hormone
(GnIH) exert an inhibitory effect on the HPG axis and
testicular Leydig cells. The resulting inhibition of the
HPG axis reduces testosterone levels. This leads to
changes in Sertoli cells and the blood–testis barrier,
which ultimately causes spermatogenesis to be sup-
pressed. Impairment of testosterone secretion forms
the main basis underlying the detrimental effects of psy-
chological stress on spermatogenesis [64]. Raised corti-
costerone levels in stressed rats were found to suppress
both testosterone and inhibin levels [65].
One study evaluated the effects of psychological
stress on reproductive hormones and sperm quality in
the male partner of infertile couples. The level of psy-
chological stress was assessed using the Hospital Anxi-
ety and Depression Score (HADS) questionnaire and
27% of the study population was found to have signifi-
cant psychological stress. Men who were significantly
stressed (HADS 8) had lower levels of testosterone,
and higher levels of FSH and LH than men with normal
HADS (HADS <8). However, GnRH levels were
unchanged. Testosterone was negatively correlated,
whilst FSH and LH were positively correlated with their
HADS. Men with HADS 8 had a lower sperm count,
motility, and normal morphology compared to those
with normal HADS. Serum testosterone levels were pos-
itively correlated, whilst LH and FSH were negatively
correlated with sperm count and motility [66].
Similarly, in an animal model study, acute restraint
stress was shown to suppress sperm motility from 30
min of restraint onwards. Plasma levels of ACTH and
corticosterone were elevated, whilst FSH, LH, and testos-
terone were decreased. It appears that the increased HPA
axis activity had inhibited HPG activity [67].
A meta-analysis of 57 cross-sectional studies involv-
ing 29 914 participants reported that psychological
stress could lower sperm concentration and progressive
motility, and increase the fraction of sperm with abnor-
mal morphology [13].
One study investigated the association between psy-
chological stress in the form of occupational, life stress,
family functioning, and semen quality. They found that
occupational stress was negatively associated with
semen quality, with a positive association between stress
and percentage of sperm with DNA damage. Satisfac-
tion with family functioning was negatively associated
with the percentage of motile sperm cells. However, life
stress did not correlate with semen quality [68]. Another
study evaluated the associations between work-related
stress, stressful life events, and perceived stress on semen
quality. Of these, perceived stress and stressful life
events were negatively associated with semen quality,
particularly sperm motility and percentage normal mor-
phology. However, work-related stress was not associ-
ated with semen parameters [69].
In another study amongst healthy volunteers, the
effect of examination stress was investigated on seminal
antioxidant content and sperm quality. During the
stressful period just before examination, seminal glu-
tathione and free sulphydryl content, as well as sperm
motility was reduced, whilst the percentage of sperm
with abnormal morphology was higher compared to a
non-stress period 3 months after examination [70].Sem-
inal antioxidant enzymes, superoxide dismutase (SOD)
and catalase were also measured. During the stressful
pre-examination period, stress scores and SOD activity
was increased, whilst sperm concentration and motility
were decreased compared to the post-examination
non-stress period. However, catalase activity remained
unchanged [71].
Psychological stress is associated with reduced pater-
nity and abnormal semen parameters, and thus could be
a causative factor in affecting male infertility.
Advanced paternal age (APA)
Advanced maternal age is defined as the age of 35 years,
beyond which there is significantly increased risks of
adverse reproductive outcome for women [72]. How-
ever, APA has not been as well-defined, with studies
commonly defining it to be between 35 and 50 years of
age or categorising it into age ranges of 5 years [73].A
meta-analysis of 90 studies involving 93 839 participants
reported an age-associated decline in semen volume,
sperm total, and progressive motility, normal sperm
morphology along with an increase in DNA fragmenta-
tion. However, despite its decline over time, sperm con-
centration did not decline with increasing male age [74].
Analysis of semen parameters of healthy men over a
wide age range (22–80 years) showed that semen volume
and sperm motility declined gradually and continuously
with age without a specific age threshold [75]. However,
a retrospective study involving 5081 men (aged 16.5–72.
3 years) suggested that the decline in sperm parameters
and its corresponding age threshold were as follows:
6 Durairajanayagam
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Arab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
total sperm count and total motile sperm - after 34 years
of age; sperm concentration and fraction of sperm with
normal morphology - after 40 years of age; sperm motil-
ity and progressive parameters of motile sperm - after
43 years of age; ejaculate volume - after 45 years of
age; ratio of Y:X-bearing sperm in ejaculates - after
55 years of age. Thus, the authors proposed that inde-
pendent of the woman’s age, the likelihood of pregnancy
declines after intercourse with men aged >34 years [76].
The exact mechanisms underlying the age-associated
decline in male fertility have not been determined [77].
These age-dependent changes in semen quality could
probably be attributed to normal physiological changes
in the reproductive tract that occur with ageing,
decreased capacity for cellular and tissue repair of dam-
age induced by exposure to toxicants or diseases, and
increased chances with age of having reproductive dam-
age resulting from exogenous exposures such as smoking
or infections [75]. The fact that both normal physiolog-
ical processes and environmental factors could be held
responsible for the effects of ageing on the male repro-
ductive system adds to its complexity [78].
As men grow older, testicular function and metabo-
lism deteriorates as the testis undergoes age-related mor-
phological changes such as decrease in the number of
germ cells, Leydig and Sertoli cells, as well as structural
changes, including the narrowing of seminiferous
tubules (reviewed in [78]). Concentrations of free and
total testosterone steadily decline with increasing male
age, leading to primary hypogonadism. Regulation of
the HPG axis is also altered as men age. Accumulation
of ROS in male germ cells throughout the course of age-
ing leads to oxidative stress and damage to sperm DNA.
Apoptosis is also increased in the ageing testes (reviewed
in [78]). These age-related changes inevitably lead to
deterioration of sperm quality and quantity.
APA-induced increase in sperm DNA fragmentation
adversely affects the success rates of ART outcomes, as
well as early embryo development [79]. A study of donor
ovum cycles indicated a 26% lower odds of live birth
with each 5-year increase in paternal age [80]. In couples
undergoing IVF, implantation and pregnancy rates
decreased with increasing paternal age when the mater-
nal age was between 30–34 years [81]. However, paternal
age did not seem to affect ART outcomes when ICSI
and good quality oocytes were used [82]. APA nega-
tively influenced the number of high-quality embryos
but did not affect pregnancy outcomes in couples under-
going ICSI cycles [83].
Independent of maternal age, APA is associated with
increased rates of spontaneous abortion and lower preg-
nancy rates amongst couples attempting to conceive
either naturally or using IUI [77]. The association
between APA and foetal loss suggests that DNA muta-
tions originating from the ageing male are detrimental
to the offspring’s health [72]. Paternal ageing causes
genetic and epigenetic changes in spermatozoa, which
could proceed through fertilisation into the offspring,
causing a variety of diseases in the resulting offspring
[78].
Therefore, couples must be counselled with equal
emphasis on the contribution of APA and advanced
maternal age as being potential risk factors of negative
pregnancy outcomes and impaired offspring health.
Diet
Diet and nutrition plays an important role in semen
quality. A recent exhaustive systematic review of obser-
vational studies concluded that intake of a healthy, bal-
anced diet could improve semen quality and fecundity
rates amongst males [84]. For example, the Mediter-
ranean diet, which is enriched with omega-3 fatty acids,
antioxidants, and vitamins, and low in saturated and
trans-fatty acids, were found to be inversely associated
with low semen quality parameters [84]. Thus, greater
compliance to the Mediterranean diet may aid in
improving semen quality [85].
Another study defined a typical ‘Western’-style diet
as one that was high in red and processed meat, refined
grains, and high-energy drinks, whilst a more ‘Prudent’
diet comprised mainly of white meat, fruit, vegetables,
and whole grains. The healthier ‘Prudent’ diet was pos-
itively associated with sperm progressive motility, but
not sperm concentration and morphology [86]. In fact,
a healthy dietary intake was reported to improve at min-
imum one measure of semen quality [87]. To begin with,
the practice of substituting processed red meats with fish
may have a positive impact on sperm counts and mor-
phology [88].
Vegetables and fruits, fish and poultry, cereals and
low-fat dairy products were amongst the foods posi-
tively associated with sperm quality. However, diets
consisting of processed meat, full-fat dairy products,
alcohol, coffee, and sugar-sweetened beverages were
associated with poor semen quality and lower fecundity
rates [84].
Caffeine
Most studies have not found an association between
moderate caffeine intake and male fertility. A large
meta-analysis with 29 914 participants found no signifi-
cant effects of coffee consumption on semen quality [13].
Another study involving 2554 young Danish men also
found no association between moderate caffeine
(800 mg/day) or cola (1 L/day) intake and reduction
in semen quality [89].
However, Belloc et al. [90] found that nearly 76% of
caffeine consumers (3.0 ± 1.8 cups of coffee/day) had a
Lifestyle causes of male infertility 7
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Ar ab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
slight increase in semen volume, whereas fertile vasec-
tomy patients who drank 6 cups of coffee/day pre-
sented with higher sperm motility [91]. A recent
systematic review involving 19 967 men found that in
most of the studies, semen parameters were affected by
cola-containing beverages and caffeine-containing soft
drinks, but not by caffeine intake from mainly coffee,
tea, and cocoa drinks [92].
Caffeine intake may impair male reproductive func-
tion possibly through sperm DNA damage. The Ricci
et al. [92] meta-analysis suggests that caffeine intake
could be associated with double-strand DNA breaks
and sperm aneuploidy, but not DNA adducts. Indepen-
dent of age, healthy non-smoking men whose daily cof-
fee intake amounted to >308 mg (2.9 cups) have
shown increased double-strand sperm DNA damage
[93]. By contrast, the Belloc et al. [90] study found that
caffeine intake was associated with a lower risk of ele-
vated DNA fragmentation (odds ratio 0.92, 95% CI
0.92–0.99).
Some studies have even reported that coffee con-
sumption in males was associated with prolonged time
to pregnancy [92]. Amongst couples undergoing IVF,
male caffeine consumption was not significantly associ-
ated with live-birth, fertilisation and implantation rates
[94]. Male caffeine intake was associated with a lower
probability of achieving a clinical pregnancy and live
birth per ART cycle, particularly in men consuming
272 mg caffeine/day [95]. Male consumption of coffee
had a negative relationship with ICSI fertilisation rate,
but did not seem to affect implantation, pregnancy,
and miscarriage rates [96]. Amongst couples with suc-
cessful IVF/gamete intra-fallopian transfer (GIFT) out-
comes, male caffeine consumption had no effect on
fertilisation, pregnancy or live-birth rates. However,
the odds of multiple gestations increased by 3.0 (95%
CI 1.2–7.4) for men who consumed an additional 100
mg caffeine daily during the week of the initial clinic
visit [97].
The potential developmental toxicity of caffeine in
the reproductive function of the male progeny has also
been examined. Men exposed in utero to increasing
maternal coffee consumption displayed a tendency
toward decreasing semen volume and testosterone
levels. Whilst current caffeine consumption in adult
males was not associated with semen quality, males with
high caffeine intake had increased serum testosterone
levels compared to those with low intake [98]. Maternal
coffee consumption during gestation and lactation
impaired gonadal development and seemed to exert per-
manent detrimental effects on the reproductive potential
of male offspring rats [99].
In summary, based on the current available data,
there is no firm potential relationship between caffeine
intake and male infertility.
Other lifestyle risk factors
Genital heat stress resulting from scrotal hyperthermia
is a substantial risk factor for male infertility. Prolonged
hours of sitting or exposure to radiant heat, varicocele,
and cryptorchidism can all lead to testicular heat stress
[100]. Elevated scrotal temperatures lead to spermato-
genic arrest, germ cell apoptosis, oxidative stress, and
sperm DNA damage [59]. Cycling as a sport is associ-
ated with increased generation of testicular heat. Intense
cycling training for 16 weeks in young healthy male road
cyclists was found to induce an increase in seminal ROS
and malondialdehyde levels, along with a decrease in
enzymatic antioxidants and total antioxidant capacity.
These changes were maintained even after 4 weeks of
recovery [101]. Furthermore, seminal interleukin levels
were raised in these non-professional cyclists and sperm
parameters were suppressed despite the 4 weeks of
recovery [102].
Sleep disturbances may possibly have adverse effects
on male fertility, as semen volume was lower in patients
with difficulty in initiating sleep, including those who
smoked or were overweight [103]. Sleep loss was found
to affect sperm function in an animal study [104]. Con-
stant use of electronic devices also contributes to poor
sleep hygiene. Exposure to radiofrequency electromag-
netic waves radiation emitted by mobile phone use could
potentially exert harmful effects on the testis [105]. One
meta-analysis found that mobile phone exposure is asso-
ciated with reduced sperm motility and viability [106],
whilst another study found this adverse effect on sperm
motility and viability occurs only in vitro [107].
Conclusion
There are a wide variety of risk factors that could poten-
tially influence sperm quality. These include lifestyle fac-
tors such as cigarette smoking, alcohol intake, use of
illicit drugs, obesity, psychological stress, APA, diet,
and caffeine intake. The adverse effects of these factors
could even become intensified from one generation to
the next, and then passed on to the resulting offspring.
However, their negative effects can be overcome to a
large extent by behaviour modification and better life-
style choices. In this manner, the harmful impact of
these factors on the male reproductive potential could
also be alleviated and thus result in a more favourable
outcome.
The evidence supporting the adverse effect of each
risk factor on male fertility, as discussed in the present
review, are of varying strength. Almost all the studies
focus on the specific effects of one or at most two risk
factors that were under evaluation. However, in reality,
exposure to these risk factors does not occur individu-
ally but rather simultaneously, with each one being at
8 Durairajanayagam
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Arab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
a varying duration and severity of exposure. It could
then be said that without insight into the broader picture
of these complex exposures, we may already be underes-
timating the consequences of each exposure.
The additive effects from the risk factors of male
infertility such as smoking and alcohol intake on sperm
parameters have been recognised. Moreover, the other
groups of risk factors of male fertility, such as environ-
mental and occupational factors, may also pose a simul-
taneous underlying threat to male fertility. Exposure to
the confounding factor(s) should also be taken into con-
sideration when planning the study design.
Perhaps by maintaining an overall positive lifestyle,
the burden of the multiple factors that could influence
sperm quality and male fecundity, may begin to slowly
improve. In that respect, awareness and recognition of
the possible impact of risk factors present in daily life
is crucial amongst couples seeking conception. As the
influence of several of these factors governing male
infertility may be reversible, therefore the couple may
benefit from early counselling and clinical intervention.
Conflict of interest
None.
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Lifestyle causes of male infertility 11
Please cite this article in press as: Durairajanayagam D. Lifestyle causes of male infertility, Ar ab J Urol (2018), https://doi.org/10.1016/j.aju.2017.12.004
