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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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