Vol 7, Issue 2, 2014 ISSN - 0974-2441

Review Article

RECENT TRENDS IN MALE REPRODUCTIVE HEALTH PROBLEMS

PALLAV SENGUPTA
Department of Physiology, Vidyasagar College for Women, University of Calcutta, Kolkata, West Bengal, India
Email [email protected]
Received: 28 November 2013, Revised and Accepted: 28 January 2013
ABSTRACT
This review critically evaluates the current trends of male reproductive health problems in relation to semen quality. Increasing trend in male
reproductive disorders observed in recent years, are principally found to associate with lifestyle and environmental factors. Lifestyle-allied diseases
could be controlled with modification in diet, living and working environment etc. This review outlines the changing trends in male reproductive
health and highlights the alterations in semen quality, in scientific manner. Though scientific and public concern regarding the changes on male
reproductive health has grown in past few decades but the demonstration of a geographical differences in sperm concentration, still appears to be
controversial. The amplitude of the difference observed cannot only be explained by methodological or confounding factors, and must to some
extent be attributed to ethnic, genetic or environmental factors. However, there are numerous reports indicating the chronologically declining
sperm count and standard semen parameters in various population indicating the increasing trend of male reproductive health disorders.
Keywords: cryptorchidism, infertility, sperm count, semen quality, testicular cancer

INTRODUCTION
Reproductive health is the basic human right which refers a state of and colleagues[8] evaluated data from Denmark, Norway, Sweden,
complete physical, social and mental well-being and not merely the the former German Democratic Republic, Finland and Poland,
absence of disease and infirmity in all matters relating to the including data on over 30,000 cases of testicular cancer from 1945
reproductive system and to its functions and processes.[1] But to 1989 in men aged 20-84. They reported considerable regional
during the past two decades, a number of reports have appeared variation in both the incidence of testicular cancer and in the
which have raised serious concerns about the development of observed rate of increase, ranging from a 2.3% increase per annum
reproductive problems in animals and man. There are numerous in Sweden to 5.2% per annum in the former East Germany. Similarly,
reports of alligators with abnormal male genital development[2] and Zheng et al.9 concluded that the increase in testicular cancer
of reproductive changes in fish and birds.[3] Simultaneously, there observed in men born after 1910 in USA was enlightened mainly by
have been controversial reports of alterations in human semen a strong birth cohort effect. However, from some other studies it is
quality (i.e. changes in semen volume, sperm concentration, sperm now clear that men with a history of cryptorchidism, inguinal hernia,
motility and sperm morphology)[4], along with reports of an hypospadias and hydrocele have a significantly increased risk of
emerging incidence of congenital malformations of the male testicular cancer.[14] It has been suggested that paternal occupation
reproductive tract, such as cryptorchidism and hypospadias[5], and before conception may alter the testicular cancer risk of
of an increasing trend of testicular cancer[6]. However, there is offspring[15], as may the parental use of pesticides or fertilizers[16]
controversy over whether or not these reported changes in male or childhood residence in areas with a high nitrate concentration in
reproductive health are genuine[7], and if so, what the causes and ground water[17]. While fathers of testicular cancer patients have
implications are, in particular the implications for clinicians caring been found to have a slight increase in their own risk of the disease,
for couples with infertility. a much more significant risk attaches to the brothers of men with
testicular cancer.[18] These latter observations support the possible
Testicular cancer involvement of a genetic component in the aetiology of testicular
Even though a lot of the changes observed in male reproductive cancer. In a case control study in the UK, Davies et al.[19] found that,
health are controversial, there seems little disagreement that while cryptorchidism was a major risk factor for testicular cancer,
testicular cancer is increasing in rate of recurrence (Fig 1A), with each extra quarter pint of milk consumed amplified the risk by 1.39-
unexplained increase in the age-standardized incidence observed in fold.
Europe (Fig 1B)[8] and the USA[9]. In the west of Scotland, the Congenital reproductive tract defects in male
number of testicular germ cell tumours registered has more than
doubled over 1990 than it was in 1960[10], while a study from The incidence of congenital malformation of the male genital tract is
Norway reported that the age-related frequency of testicular cancer also changing its pattern, with increase in the prevalence of
increased from 2.7 per 1 lakh individuals in 1955 to 8.5 per 1 lakh cryptorchidism and hypospadias[20]. Cryptorchidism has increased
individuals in 1992.6 A similar study reported 61% increase in by as much as 65-77% over recent decades in the UK5, while USA
testicular cancer in southern Norway from 1986-87 to 1991-92.6 In data have shown that rates of cryptorchidism have not changed[21],
the USA, the overall age-related incidence of testicular and germ cell although a large study from the USA reported that rates of
cancer has increased 3.5-fold during the past 60 years (Fig 2).9 There hypospadias have doubled between the 1970s and 1980s[22]. In one
is considerable geographical variation in both the occurrence of Kallen et al.[23] who conducted a multicentre study of 8,122 boys
testicular cancer and in the observed rate of its growth[11]. This from seven malformation surveillance systems around the world,
geographical variation may be linked with that observed in semen resolved that a true geographical variation exists in the prevalence
quality - testicular cancer is four times more common in Denmark, of hypospadias at birth. Berkowitz et al.[24] who were considering
where studies have shown low sperm concentrations in men[12], at the risk factors for cryptorchidism, suggested that
than in Finland where sperm concentration is higher[13]. Bergstrom maternal obesity, low birth weight, the presence of other congenital
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malformations, ethnic group and a family history may be relevant. methods of subject recruitment and laboratory technique, during a
Others have 20 year period. They observed a fall in all of the classical measures
of semen quality over time. Sperm count was found to be affected by
suggested strong associations between cryptorchidism and low age with each year of advancing age being associated with a 3.3%
social class[25]. fall in sperm concentration. An accompanying editorial by
Altering semen quality Sherins[45] unfortunately misinterpreted this study as being
concerned with men selected as sperm donors, rather than potential
Classical reports donors, and thus raised concerns about selection bias that were not
well founded. Numerous other groups have published data
The proposition that semen quality is changing is not new. In 1974,
proposing a secular trend in semen quality amongst normal men.
Nelson and Bunge[26] reported data on 386 men presenting for
Irvine et al.4 later observed that the median sperm concentration fell
vasectomy in the USA. The mean sperm concentration of this group
from 98×106/ml among donors born before 1959 in Scotland to
was 48×106/ml, only 7% of them were reported to have sperm
78×106/ml amongst donors born after 1970. In a similar study, Van
concentrations above 100×106/ml which is far below than the
Waeleghem et al.[46] observed declines in sperm concentration
concentrations reported in the earlier studies of 120×106/ml[27],
from a mean of 71×106/ml to 58.6×106/ml in sperm donors of
145×106/ml[28] and 100.7×106/ml[29] respectively. In 1951,
Belgium.
MacLeod and Gold[30] had published their landmark study of semen
quality in 1,000 male partners in infertile relationships, together In contrast, a number of reports have failed to find any evidence of a
with a similar number of men of proven fertility and reported an secular trend in semen quality. In a study of 302 volunteer semen
average sperm concentration of 107×106/ml, with 5% of them donors in Toulouse, France, between 1977 and 1992 no evidence of
having sperm concentrations under 20×106/ml, and 44% having changes in semen quality with time was observed[47].
above 100×106/ml. Nelson and Bunge26 speculated that their data Handelsman[48] also found no evidence of any effect of year of
‘would tend to incriminate an environmental factor to which the observation or year of birth on sperm concentration, total sperm
entire population has been exposed’26. Later, several reports of number or ejaculate volume. Later two significant reports from the
semen quality in fertile men found intermediate values for average USA have provided evidence of unchanging semen quality in the
sperm concentration of 70×106 - 81×106/ml[31]. Then MacLeod and populations studied of Fisch et al.[49] and Paulsen et al.[50] De
Wang[32] who investigated infertile marriages reported that there Mouzon et al.[51] have published the largest retrospective review of
was no evidence of a general drop in semen quality. Leto and semen quality data. On the basis of the French national in vitro
Frensilli[33] reported a decline in semen quality amongst potential fertilization (IVF) register, they reviewed the results of 19,848
semen donors. In 1980, James[34] reported the first review of semen analyses from 7,714 men undergoing IVF for tubal disease,
published data on semen quality in men of proven fertility and in and having a normal semen analysis prior to IVF. They found a
unselected normal men. Bostofte et al.[35] compared 1,077 Danish significant decrease in semen quality with later year of birth, the
men presenting for evaluation of infertility in 1952 with 1,000 average sperm concentration in men born before 1939 being
similar men presenting 20 years later in 1972. They observed a 92.5×106/ml, falling to 77.1×106/ml for men born after 1965. In a
significant drop in sperm concentration, a decrease in sperm smaller study, Berling & Wölner-Hanssen[52] reported on semen
motility and an increase in the proportion of abnormal spermatozoa. quality in 718 semen samples submitted by infertile men from 1985
Similar findings were reported in a Swedish study in 1960-61.[36] to 1995 in one Swedish centre and found no relationships with age
These early publications failed to raise major public health concerns, or date of birth, although ejaculate volume seemed to decrease and
perhaps because the data came from selected groups of men, normal morphology, motility and sperm penetration of hyaluronic
unrepresentative of the general population, including men attending acid polymer increased during the study period.
infertility clinics[36] or semen donors[33,37].
Most recently, a very careful reanalysis of the historical data[12] on
Jensen et al.[12] in 1992 reawakened concern over the possibility of semen quality in normal men has been published[53]. These
secular trends in semen quality, publishing a meta-analysis of data workers used multiple linear regression models, controlling for
on semen quality published since 1930 in normal men. Data were abstinence time, age, the proportion of the sample with proven
obtained on 14,947 men, published in 61 papers during 1938-1990. fertility, specimen collection method, study goal and geographical
Using linear regression, they observed a decline in average semen location to examine regional differences and the interaction between
volume from 3.40 ml in 1940 to 2.75 ml in 1990. A similar analysis region and year of publication. Using a linear model, they found that
for sperm concentration suggested an apparent decline from sperm concentrations and the rate of decline in sperm concentration
113×106/ml in 1940 to 66×106/ml in 1990. There was no change in differed significantly across regions. They concluded that there was
the average age of the men studied, and no apparent influence of age evidence of a decline in sperm concentrations in the USA of
on the observed secular trend in semen quality. Predictably, the 1.5×106/ml per year, and in Europe of 3.13×106/ml per year, but not
central message of this meta-analysis, that sperm counts had in non-Western countries. Results were similar when other (non-
declined by about 50% over the past 50 years, attracted enormous linear) models were used, and these workers concluded that their
attention and generated much controversy[38,39]. Bromwich and results were unlikely to be due to either confounding or selection
colleagues38 later speculated that much of the apparent change in bias53. Thus, the available literature on secular changes in semen
semen quality could be accounted for by a change in the ‘accepted’ quality is, at best, inconclusive. To a greater or lesser extent, all of
definition of the lower limits of ‘normal’ semen from around the available data suffer from the problems of being retrospective,
60×106/ml in the 1920s[40] to 20×106/ml, which is the figure collected in different countries, at different times, using different
commonly accepted today [41]. However, it has been pointed out methods of subject selection and recruitment and different
that at least some of the earlier papers did include men with semen laboratory methodology. The retrospective nature of the data means
quality in this range[42]. Keiding and Skakkebaek [43] then pointed that control of important confounding variables is often imperfect,
out, all of the statistical models agree on one qualitative message - a weakening the conclusions reached. More evidence is clearly
decline in semen quality over time. However, it is surely legitimate needed, yet one is tempted to wonder whether the inherent
that all the available data, as presented, even if imperfect, help to difficulties in laboratory methodology, subject selection and the
define questions and priorities for future study. large number of potential confounding variables involved mean that
it may never be possible to resolve the issue of secular trends in
Recent reports
human semen quality with certainty.
Most of the reports that appeared closely after the meta-analysis of
Regional variations
Jensen et al.12 provided alternative interpretations of the data.
Unfortunately, the available data still fail to reach a definite Although the position with regard to secular changes in semen
conclusion as to whether or not there is any secular trend in semen quality remains unclear, an important observation to emerge from
quality. Auger et al.[44] published data on semen quality in fertile this work is the striking regional differences that are apparent: for
Parisian men by examining 1,750 fertile men with consistent example, the above mentioned study by Fisch et al.49, in which sperm

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concentrations were highest in New York (131.5×106/ml), diethylstilboestrol during pregnancy have an increased incidence of
intermediate in Minnesota (100.8×106/ml), and lowest in California cryptorchidism and hypospadias at birth, and of abnormal
(72.7×106/ml). The Seattle data, with a geometric mean of spermatogenesis in adult life[83]. It is not clear whether they are
46.5×106/ml, is not directly comparable50. Within Europe, similar any less fertile as a result[84]. The effect on testicular descent, and
patterns can be observed. Semen quality in normal Finnish men perhaps also on increase in testis cancer risk, would presumably be
would appear to be high, with a mean sperm concentration of mediated through interference with the secretion of müllerian
133.9×106/ml being reported13, whereas in Paris and Edinburgh inhibiting substance (MIS)[85]. Testicular cancer may also be a
lower mean values of 98.8×106/ml and 104.5×106/ml have been congenital condition that becomes manifest at or after puberty[86].
reported 4,44. In contrast, semen quality in normal men in Belgium Thus, the understanding of the development of the male
has been reported at 66.8×106/ml, and in Denmark at 69.2×106/ml reproductive system leads to the conclusion that exposure to
12,46. Whether or not there are also regional differences in the exogenous oestrogens may perturb it in such a way as to give rise to
occurrence or otherwise of secular changes in semen quality is the changes which appear to be emerging in human health. There is
unknown47, but it is evident that geography is a vital confounding certainly concern over the growing number of chemicals that may be
variable which should be considered when examining such data[54]. viewed as ‘endocrine disrupters’. The Danish EPA has recently
One study reported deteriorating semen quality in a group of released a report raising concern over environmental chemicals
patients resident within the area of one water supply company, but with oestrogenic effects76, whilst recent commentaries in the
no change in the semen of similar patients living nearby[55]. Data Lancet[87] and British Medical Journal[88] have highlighted the need
from the Centres d’Étude et de Conservation des Oeufs et des for further research in this complex area. It is clear that there are
Spermes Humaines (CECOS)[56] has provided strong support for the chemicals in the environment which are ‘oestrogenic’, and which can
existence of regional differences within France, and the recent meta- perturb sexual development in exposed animals[89]. In mammals, it
analysis by Swan et al.53 noted that intraregional differences were at has been shown that exposure of pregnant mice to ethinyloestradiol
least as large as the mean decline in sperm concentration. It is increases the frequency of gonadal dysgenesis, cryptorchidism and
possible that these regional differences, which might be due to testicular cancer, in association with impaired Leydig cell
ethnic, environmental or lifestyle factors, could provide a valuable development and reduced Sertoli cell numbers[90] Gestational
tool in addressing the hypothetical causes of changes in semen exposure of rats to xeno-oestrogens has been shown to result in
quality4. Using time taken to achieve a pregnancy in fertile couples reduced testicular size and sperm production[91] and we now know
as a measure of fertility[57], Joffe[58] examined antenatal that exposure of pregnant sheep to xeno-oestrogens supresses foetal
population and cross-sectional studies in Finland and the UK. In both FSH. In an attempt to estimate the familial and genetic contributions
comparisons, fertility was significantly greater in Finland than the to variation in human testicular function, Handelsman[92] has
UK. The author therefore concluded that ‘the previously reported studied 11 pairs of monozygotic and 6 pairs of dizygotic twins, and
difference in sperm counts between Finland and elsewhere in north- observed that sperm concentration, testicular size and sex hormone
west Europe (including Great Britain) is probably not binding globulin (SHBG) all had a strong familial effect, but was
artefactual’[57,58]. This along with some other reports suggest that unable to confirm any genetic component.
the reported worldwide decline in semen quality is also real (Table
1). CONCLUSIONS

Factors contributing reproductive health disorders and altering Although the ‘environmental oestrogen’ hypothesis has attracted
semen quality much attention, and there exist some biological data to confirm its
plausibility, evidence that it is causally related to changes in human
The cause of these observed changes in male reproductive health male reproductive health remains circumstantial. The evidence for
remains unidentified. It is clear that lifestyle factors such as secular changes in semen quality and other changes in male
occupation[72], smoking[73], dress habits[74] and even time spent reproductive health is indecisive, with the exception of testicular
commuting[72] may be relevant. However, the hypothesis that has cancer, though evidence for regional differences in male
attracted most attention concerns exposure to environmental xeno- reproductive health would appear to be stronger. In both cases,
oestrogens during development[75]. This is now a large and association does not imply causality, and several other possible
complex field, reviewed recently by the Danish EPA (Danish explanations require to be considered. As far as semen quality is
Environmental Protection Agency)[76]. Sertoli cells play an concerned, sperm count is a poor index of fertility, and there are as
important role in regulating the environment within the yet, no data on secular changes or regional differences in sperm
seminiferous tubules, each Sertoli cell supporting the development function, although there may be some evidence of regional
of a limited number of germ cells[77]. Any perturbation in the differences in fertility. While the available evidence is inconclusive
development of the reproductive system that leads to a reduction in and circumstantial, its weight is considerable and at the very least it
Sertoli cell number will reduce the individual’s ultimate capacity for should raise concerns that deserve to be addressed by properly
sperm production in adult life. In most mammals, Sertoli cell designed, coordinated and funded research. Delay may compromise
replication occurs during foetal and postnatal life, Sertoli cell the fertility and reproductive health of future generations [4,88].
number becoming fixed at some stage of development. In the rat,
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