Sperm counts, testicular cancers, and the environmentBMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j4517 (Published 10 October 2017) Cite this as: BMJ 2017;359:j4517
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In a society that seems to readily ignore issues with male fertility, be it through lack of scientific knowledge or simply masculine embarrassment, it was great for this week’s print editorial to highlight the topic.  However, the article has made a number of assumptions which lower the reliability of its conclusions. First is the idea the EDCs are the main cause of declining sperm quality, which has been pinpointed as flawed by some of the article’s responses, but also the suggestion that sperm quality is the only factor in declining total fertility rates (TFR). This means the article exaggerates the effects of poor sperm quality in the present day.
The meta-analysis by Levine shows that total sperm count (TSC) and sperm concentration (SC) have declined since 1973.  As an overall trend this is correct, yet it is far from the whole picture. It should be noted, for starters, that these data were collected from a huge number of studies over the period of 1973-2011. Many samples were taken from fertility clinics, where sperm quality amongst male visitors is already low enough for them to be seeking help with conception. Growth in abundance of these fertility clinics has caused a steady increase in data available from such establishments, leading to a skewed view of sperm quality in the overall population as the ratio of known low sperm quality samples to other available samples has got larger over time. In fact, primary data collected for the sole purposes of studying declining sperm quality has concluded that both TSC and SC are increasing in the young population. 
Furthermore, even though the Levine analysis reveals a decline in sperm quality over the past 44 years, it also shows that both TSC and SC are well above what the WHO consider to be a low sperm count.  Looking at the data the average TSC in recent studies is 4.7x10(7)/ml; when SC reaches 4.0x10(7)/ml the likelihood of conception stays roughly the same no matter how much greater the concentration gets. Many sufferers of oligospermia with half this concentration will go on to conceive naturally within two years anyway. 
Focussing on declining sperm quality therefore cannot be the way to deal with the falling fertility rate in the west. Instead of a “holistic view of male reproductive health problems”, a holistic view of every medical and environmental factor must be employed. Take Japan as an example. It is particularly interesting regarding this issue because the country has an aging population resulting from its low birth rate combined with the highest life expectancy in the world.  The population is living longer so there is no sense in urgency for marriage or conception as more time is available in a person’s lifetime for both.
On top of this, Japanese culture has incredibly traditional values. If a woman marries she is expected to bear children and then stay at home to care for them; styling life like this is not of great appeal to the current youth, so women are putting off marriage to instead spend time finding fulfilment in their careers and reaching professional success. This is shown in the decline in marriage rates and later marriages that correlate with an increase of females in the workforce.  More fertility treatments and options are also available for those who want to delay childbirth. The ability to freeze eggs is relatively new, but women are happy to pay for this so they can conceive beyond menopause and public funding is available for this procedure in some areas to try and combat the low birth rate.  There has in fact been a small climb in TFR in the past three years, probably due to the “tempo effect” whereby catch up occurs after an entire generation changes the average age they have their first child. 
A diminishing fertility rate is seen in all developed countries, though. In Europe no countries match the replacement rate of 2.1. Most western nations also fall below this, not necessarily because of disregard to traditional values but because of other local influences. Some simple examples of this follow. Fewer people are theists, meaning teachings about traditional family values are less apparent and the idea that sexual intercourse is for solely reproduction has lost its hold. Sex education is now a prominent part of childhood learning and people know about the methods of contraception available, all of which are easily accessible in developed countries. Cost of raising a child has also gone up meaning would-be parents are put off having more than one child, if any at all.
It’s important not to overlook statistics showing declining TSC and SC, and more research should be done surrounding low sperm quality and it’s causes to prevent any future decline, but it is currently not as large an issue as has been made out. Fertility rates below the replacement rate is the problem the western world currently faces but this cannot be tackled from a purely medical stand point. Cultural aspects of life currently have the greatest influence on TFR, and these mentalities are very hard to change as they are embedded into entire generations. (At the same time the world must be wary. Whilst developed nations do have a low birthing rate, the world currently averages out at 2.5, as some countries reach heights of 7.6. )
Whilst it is hard, nigh on impossible, to give a definitive cause for low TFR in western countries, what can be said for certain is this. Sperm quality is not the main cause of low fertility in the developed world, and the only way we can begin to tackle extreme shortfall from the replacement rate across different countries is to consider everywhere individually and target resolutions to each area based off all cultural and scientific data to hand.
1. Skakkebaek Niels E. Sperm counts, testicular cancers, and the environment BMJ 2017; 359 :j4517
2. Hagai Levine, Niels Jørgensen, Anderson Martino-Andrade, Jaime Mendiola, Dan Weksler-Derri, Irina Mindlis, Rachel Pinotti, Shanna H Swan; Temporal trends in sperm count: a systematic review and meta-regression analysis, Human Reproduction Update, Volume 23, Issue 6, 1 November 2017, Pages 646–659, https://doi.org/10.1093/humupd/dmx022
3. Jørgensen N, Joensen UN, Jensen TK, et al; Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men, BMJ Open 2012;2:e000990. doi:10.1136/bmjopen-2012-000990
4. Cooper TG, Noonan E, von Eckardstein S, et al. (2010). "World Health Organization reference values for human semen characteristics". Hum. Reprod. Update. 16 (3): 231–45. PMID 19934213. doi:10.1093/humupd/dmp048.
5. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Bonde, Jens Peter EHenriksen, Tine Brink et al. The Lancet , Volume 352 , Issue 9135 , 1172 – 1177
7. Ministry of Internal Affairs and Communication, Statistics Bureau. "Japan Statistical Yearbook, Chapter 2: Population and Households".
9. Harding, Robin (4 February 2016). "Japan birth rate recovery questioned". Financial Times. Retrieved 21 February 2016.
Competing interests: No competing interests
It is welcome that Professor Skakkebaek highlights the increasing trend in impairments of the male reproductive system.1 But there are serious errors in his account in relation to the cause(s). He focuses on endocrine disrupting chemicals (EDCs) as the likely culprit. But it is one thing to say that endocrine disrupting chemicals can affect reproduction, which may be true. It is quite another to suggest that they explain the epidemiological findings of observed deterioration. For example, inorganic arsenic is a cause of lung cancer, but nobody suggests that it was behind the lung cancer epidemic of the 20th century – this was due to cigarette smoking.
EDCs are clearly not responsible for the epidemic of the most serious of the conditions, testicular cancer. Its rapid rise started not in “the past few decades”, “recent decades”, or “a couple of generations” ago. It began in the first decade of the twentieth century in north-western Europe,2 and probably earlier in England and Wales.3 This is decades before the introduction of any known endocrine disruptor: widespread exposure started only in the 1950s.
Semen quality impairment is also not mainly due to endocrine disruption: the characteristic type of human male infertility is oligoasthenoteratospermia (OAT) – sperm are too few, motility is low, and abnormal morphology is widespread. In the good-quality studies of semen quality trends, when a decline in sperm concentration and number has been observed, motility and morphology have also deteriorated.4-6 Endocrine disruption, even if it reduces sperm concentration/number, has no plausible effect on motility or morphology.
There are several other grounds to doubt the magnitude of the impact of EDCs on male reproduction.7 These include the actual exposures relative to the toxic levels, and the expected spectrum of effects in contrast to what is observed. 7
The rapid trends, especially in testicular cancer, strongly suggest an environmental cause, as Skakkebaek says. But this does not rule out “alterations in our genome” – “genetic” is here conflated with “inherited”. The genome of germ cells can be damaged by environmental exposures, just as with mutations in somatic tissues. The evidence, experimental and clinical as well as epidemiological (including genetic studies), suggests environmentally caused damage to the genetic apparatus of the germ cells, that can be passed down through the male line.8,9 This fits with the well-established, but frequently disregarded, fact that humans have poorer semen quality, a lower conception probability, an increased aneuploidy risk (e.g. Down syndrome), and a higher risk of embryonic loss (early miscarriage) compared with other mammals; germ-cell testicular cancer is rare in non-human mammals too.9
The endocrine disruption hypothesis has dominated research in this area for 25 years now, despite its clear shortcomings. Yet Skakkebaek claims “little has been done”. I agree with him about the need for more research into reproductive health, but a far broader remit is required.
When miscarriages of justice occur, one tragedy is that innocent people are incarcerated. A second is that the perpetrators go free. By focusing on endocrine disruption, we are failing to discover the true cause(s) of the dramatic deterioration in the health of the male reproductive system in the past 110 years.
1. Skakkebaek NE. Sperm counts, testicular cancers, and the environment. BMJ 2017;359:j4517 doi: 10.1136/bmj.j4517
2. Bergström R, Adami H-O, Möhner M, et al. Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J Natl Cancer Inst 1996;88:727-33.
3. Davies JM. Testicular cancer in England and Wales: some epidemiological aspects. Lancet, 1981;I,928-32.
4. Auger J, Kunstmann JM, Czyglik F, Jouannet P, et al. Decline in semen quality among fertile men in Paris during the past 20 years. N Engl J Med 1995;332:281-85.
5. Van Waeleghem K, De Clercq N, Vermeulen L, Schoojans F, Comhaire F. Deterioration of sperm quality in young healthy Belgian men. Hum Reprod 1996;11:325-29.
6. Irvine S, Cawood E, Richardson D, MacDonald E, Aitken J. Evidence of deteriorating semen quality in the United Kingdom: birth cohort study in 577 men in Scotland over 11 years. BMJ 1996;312:467-71.
7. Joffe M. What harms the developing male reproductive system? In Male-mediated developmental toxicity, ed. Anderson D, Brinkworth MH, 2007, Royal Society of Chemistry, chapter 4, 28-50.
8. Joffe M. Genetic damage and male reproduction, In: Reproduction and Adaptation [AS Parkes Memorial volume], ed. Mascie-Taylor CGN, Rosetta L, 2011, Cambridge University Press, Cambridge, 17-49.
9. Joffe M. What is wrong with the human reproductive system? J Genit Syst Disor 2016;S2. http://dx.doi.org/10.4172/2325-9728.S2-002
Competing interests: I am the originator of a rival hypothesis concerning human reproductive and genetic impairment in both sexes, which is based on the synthesis of evidence from diverse sub-disciplines.
This is a provocative piece by the editor. It has been well flagged in the aquatic kingdom also. The feminization of male fish and other aquatic animals such as alligators turtles and frogs is well documented. It is called intersex change and is characterised by the finding of female eggs in male testes. 1 These are not hermaphrodites but were true males. The scientists involved in the study of this emerging phenomenon attribute this change to environmental pollutants. Among the culprits since the inception of global industrialization, steroidal estrogens have become an emerging and serious concern. Worldwide, steroid estrogens including estrone, estradiol and estriol, pose serious threats to soil, plants, water resources and humans. Indeed, estrogens have gained notable attention in recent years, due to their rapidly increasing concentrations in soil and water all over the world. Concern has been expressed regarding the entry of estrogens into the human food chain which in turn relates to how plants take up and metabolise estrogens. 2 As an indication to the scale of the problem 70 to 100% of small mouth bass sampled from 19 sites in the US had intersex change!
Fertility level is one manifestation of hormonal health and another is sex appropriate behaviour. It is not unreasonable to suggest that the "new man" is not just a cultural animal secondary to societal trends. He may also have a touch of the intersex phenomenon suffered by his fishy friends and be unable to maintain a gentlemanly masculinity in keeping with the times - because he just hasn't got the hormones! Cultural swing in the past 50 years is widely acknowledged to be toward feminization. 3 Environmental pollutants and in particular agents that block hormonal action are beginning to take their toll. Such phenomena have not been reported in the non-Western World. Are stellar sportsmen and male Olympic medallists over represented south of the equator? Just a suggestion...?
1. Lindsey Konkel. National Geographic. Feb 3; 2016.
2. Environmental impact of estrogens on human, animal and plant life: A critical review.
3. Denis Prager. National Review. Nov 3; 2015.
Competing interests: No competing interests