Are Men Doomed?

The decline in men’s reproductive health
Peter T. K. Chan M.D., C.M., M.Sc., F.R.C.S.(C), F.A.C.S.
Director of Male Reproductive Medicine, Department of Urology
McGill University Health Center

In ours and many other cultures and societies, the responsibility for fertility and the role of having children fall traditionally to the woman’s side. As a result, when a couple experiences infertility, it is usually the female partner who initiates a consultation with her gynecologist. Evaluation on the male side is often delayed, or even bypassed altogether. Even healthcare professionals specializing in reproductive medicine may hold the opinion that so long as there are enough sperm for assisted reproductive technology, male reproductive health evaluation and counseling are non-essential.

In reality, most male fertility specialists agree that male factor infertility can be found in about half of the couples experiencing infertility. For those who still think that male reproductive health is unimportant, here are some of the current issues on the subject to consider: 1) Many investigators worldwide reported a gradual decline in the semen quality in men over the last 50 years; 2) the rate of testis cancer has been increasing for at least ten years now; 3) Malformations of the genitals, including undescended testis (cryptorchidism) and shortening of the penile urethra (hypospadius) are becoming more commonly found in male infants. Together these observations suggest a dysfunction of the male reproductive organs, a condition termed “testicular dysgenesis syndrome” by some investigators (Sharpe & Skakkebaek, 2008).

The decline in men’s reproductive health

Human semen parameters are among the narrowest in all mammalian species. According to the World Health Organization (WHO 1999), in the average male we can expect to find as low as 25% of sperm that are “fast swimmers,” or in rapidly progressive motion. Only 14% of human sperm is expected to pass the strict criteria of forms and shape (morphology). Imagine writing an examination at school and getting a score of 14 or 25%. Surely you would have failed. Yet this is the “standard” for human sperm! In fact, it has been suggested that the current WHO sperm density standard of 20 million sperm per milliliter of semen should be lowered to 10 million per milliliter so that fewer men will be labeled to have “abnormal” sperm counts.

The decline in sperm count in men was first reported in 1992, in an analysis of 61 studies on close to 15,000 men who were healthy and fertile. The authors concluded that the mean sperm count decreased by 50% from 1938 to 1990 (Carlsen et al., 1992). Subsequently, other investigators evaluated men in different parts of the world and came to a similar conclusion: that sperm quantity and quality in men are declining (Auger et al., 1995; Irvine et al., 1996; Adamopoulos et al., 1996; Almagor, 2003), although other studies have failed to confirm these findings (see Fisch 2008).

Malformations of the male reproductive organs in newborns, such as cryptorchidism and hypospadius, are becoming more and more common. The development of sex organs in male and female fetus begins in a similar fashion. But in the male fetus, under the proper effect of androgenization (the release of male hormones), the gonads descend to the scrotum as testicles, and the penis develops with the accompanying urethra at birth. Cryptorchidism and hypospadius thus represent the end result of defective androgenization. Cryptorchidism has been linked to subsequent infertility in adulthood and increased risks of testis cancer. Thus there may be a biological link to explain the recent observation of declined semen parameters and the increased incidence of testis cancer.

The worldwide increase in testis cancer is of particular concern. Among men at reproductive age (18-35 yearrs), testis cancer is the most common solitary cancer. Often, testis cancer presents as a painless hard mass in the testis and the patient may ignore it for weeks or months before seeking any medical help. In fact, physicians may mistakenly put the patients on antibiotics thinking that it is an infection. Although testis cancer is highly curable, it is a fast growing cancer, and distant metastasis to lung, brain, retroperitoneum (space behind the abdominal wall) and mediastinum (chest area between the lungs, including the heart) can occur if diagnosis delayed.

Impact of environmental contaminants on male reproductive health

Among the various explanations of these findings that indicate a decline in male reproductive health is the possibility of various environmental contaminants that have a negative impact on reproduction. Since the Second World War, the list of chemicals, both natural and synthetic, that humans are exposed to has been growing dramatically. Currently, according to the Environmental Protection Agency of the United States, there are close to 90,000 chemical substances are registered for commercial use (US Environmental Protection Agency 2006). These chemicals include environmental pollutants such as pesticides and herbicides, volatile organic compounds, heavy metals and air contaminants. In addition to being hazardous to the general health, many environmental contaminants can affect the reproductive system. Of particular interest is a class of chemicals known as endocrine disrupting chemicals (EDCs). These chemicals interfere with the physiological actions of natural hormones such as estrogens, androgens and thyroid hormones, the hormones in the body that are responsible for the regulation of the reproductive function.

Examples of endocrine disrupting chemicals in the environment

Examples of EDCs include polychlorinated biphenyls (PCBs), bisphenol A (BPA), phthalates and certain pesticides (e.g. vinvlozolin, dicofol, atrazine). PCBs are used extensively as insulators in electrical equipment, as plasticizers in polyvinyl carbonate (PVC) products, in carbonless copy paper, as de-inking solvents for recycling of newspaper, and as waterproofing agents. Bisphenol A is the building block of several important plastics, with an estimated annual production of 2-3 million metric tons. It is used in the manufacture of eating utensils, including formula bottles for babies. It is also found in the plastic lining of food and soft drink cans. Phthalates are among the most abundant industrial chemicals in the environment. They are used in the production of various plastics and are found in consumer products such as flooring and wall coverings, food contact applications, medical devices (e.g. intravenous tubing, medication coatings), personal care products (e.g. perfumes, lotions, cosmetics), solvents and varnishes.

Historically, one of the better-studied endocrine disruptors is diethylstilbestrol (DES), a synthetic estrogen prescribed for pregnant women from 1938 to 1971, in the mistaken belief that it would prevent miscarriage. It was estimated that between two and eight million pregnancies worldwide may have been treated with DES. In addition to various adverse health outcomes in female offspring of these pregnancies (vaginal cancer, anomalies in reproductive tract, infertility and poor pregnancy outcomes), male offspring of these pregnancies were found to have an increased incidence of genital anomalies, including cryptorchidism and hypospadius, and increased risks of infertility, prostate and testicular cancers.

Other environmental risks to reproductive health

It should be noted that many other environmental contaminants can also affect reproductive health. For instance, lead was identified as an abortifacient (a substance that causes spontaneous abortion) and a cause of male infertility and impotence even in the time of the Roman Empire. Other examples of metal environmental contaminants that can affect reproductive health include mercury, manganese and cadmium. Cigarette smoke, including active or passive smoking, has been associated with decreased semen quality and other adverse reproductive outcomes. Even electromagnetic waves from electrical appliances, including mobile phones, which have evolved to become more and more powerful in their transmission capacity, have been implicated in reducing male fertility.

How do environmental toxins affect reproductive health

It should be noted that the impact of environmental toxins on reproductive health is not limited to men. Female reproductive disorders, adverse pregnancy and fetal outcomes have all been linked to various environmental toxins. Why are there so many of these “bad chemicals” around? Why were they not tested and banned by the appropriate agencies before their widespread use in consumer products?

In fact, many of these products have been “tested” and were considered “safe.” However, many of these studies were not done on humans. Conclusions drawn by extrapolating the findings from animal studies to human beings may have limited validity. Also, many of these studies were done at a high exposure dose over a short period of time. The impact of these chemicals at a low dose but over a long duration of exposure in humans is unknown. Finally, the “safety” of these chemicals was established based on the absence of problems on the general health rather than specifically on reproductive health. Hence, many of negative impacts on reproductive health were only discovered much later when the chemicals had been in use for long time.

While some environmental contaminants may affect male reproduction through direct testicular toxicity, others may affect male fertility and reproduction through more subtle mechanisms such as interference with the hormonal balance (as in the case of most endocrine disrupting chemicals). For many other contaminants, the exact mechanisms of how they affect reproductive health are largely unknown. In fact, most studies on the impact of these chemicals are only able to demonstrate an association between exposure and the risk of infertility, which may or may not mean that one is necessarily causing the other. And evidence at this level is not available for most of the chemicals that may potentially be harmful to our reproductive health.

Research in this crucial area of reproductive toxicology is particularly difficult to carry out. First, a large volume of resources is required for this type of observational or epidemiological research: in other words, thousands of men who are exposed to a particular chemical must be evaluated for their reproductive health. Second, the timing of exposure, whether it occurred during the prenatal, intra-utero or pubertal period or at reproductive age may make a tremendous difference on the subsequent impacts to reproductive health. Finally, the observed impact to reproductive health may be due to the combined effects of more than one chemical, as humans are exposed daily to a mixture of environmental contaminants and their breakdown products in air, water and food. In a recent bio-monitoring study of over 150 contaminants, the US Centers for Disease Control and Prevention (2005) reported that all 150 chemicals were detected in a portion of the US population. Some chemicals such as tobacco smoke, lead, mercury and phthalates are detected in nearly the entire population. Other contaminants, such as phthalates, may affect reproductive health in an additive manner. Thus, focusing on a single environmental toxin may underestimate its actual health risks.

What can we do about it?

The following steps may help you take control of your reproductive health.

Adopt an active attitude towards environmental impact issues. It is easy to think that as an individual, you have little or no control over the effects of environmental toxins. In fact, keeping yourself informed of the growing volume of information on the impact of environmental toxins can help you minimize your risk of exposure to these chemicals.

Let the politicians and policy makers hear your voice. Along the same lines, allowing your voices and opinions on these issues to be heard by policy makers and the government is important. Policy does change. A good example is the banning Bisphenol-A in Canada, in effect since October 2008. The six largest US companies to produce baby bottles commercially decided to stop using bisphenol A in their products. A NY county decided to ban baby bottles and toddler sippy cups made with bisphenol A.

Avoid additional risk factors that can further compromise your reproductive health. Smoking, stress, obesity, illicit drug use and many other factors that are known to compromise your fertility status should be avoided.

Have a regular check up with your doctor. Many male-factor infertility causes have better chances of improvement when discovered early.

Do not delay forming your family. It is a well-known fact that ageing has a significant negative impact on reproductive health in women. However, the latest studies have demonstrated that, though at a less severe level than in women, ageing in men has a significant negative impact on sperm count and quality, and increases the risk of transmitting various hereditary conditions including down syndrome, autism and schizophrenia (Krishnaswamy et al., 2009). Since most environmental toxins may have a dose accumulation effect, in theory, delaying having children may put you at risk of a further decline in your fertility potential.

Support reproductive toxicology research. Active research is the only way we can have scientific-based evidence to help us to make better decisions. Various societies have scientists focusing their research on various topics of toxicology. Check out the website of The Society of Toxicology of Canada (www.stcweb.ca).

Take part in protecting the environment. Minimizing the use of unnecessary synthetic products (plastic bags, bottles, printing paper, etc.) will in the long run reduce chemicals released to the environment.

Live healthily. Daily exercise, weight management, a healthy diet with adequate fresh fruits and vegetables are important for your general and reproductive health.

Get your partner, family and friends informed. Fertility has always been viewed as a private and sensitive issue that is not discussed in depth among friends and family. By taking an active step to share what you know with your friends and family, you can lead them to be aware of the issue.

References

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Almagor M, Ivnitzki I, Yaffe H, Baras M. Changes in semen quality in Jerusalem between 1990 and 2000: a cross-sectional and longitudinal study. Arch Androl. 2003 Mar-Apr;49(2):139-44.

Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in semen quality among fertile men in Paris during the past 20 years. N Engl J Med. 1995 Feb 2;332(5):281-5.

Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12;305(6854):609-13. Review.

CDC, Third national report on human exposure to environmental chemicals, Centers for Disease Control and Prevention, Atlanta, GA (2005).

Fisch H. Declining worldwide sperm counts: disproving a myth. Urol Clin North Am. 2008 May;35(2):137-46, vii. Review.

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 Feb 24;312(7029):467-71.

Krishnaswamy S, Subramaniam K, Indran H, Ramachandran P, Indran T, Indran R, Aziz JA. Paternal age and common mental disorders. World J Biol Psychiatry. 2009 Feb 3:1-6

Sharpe RM, Skakkebaek NE. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil Steril. 2008 Feb;89(2 Suppl):e33-8. Review.

US EPA, What is the TSCA Chemical Substance Inventory. Vol. 2007, US Environmental Protection Agency, Washington, DC (2006).

World Health Organization: WHO Laboratory Manual for the Eamination of Human Semen and Sperm-Cervical Mucus Interaction. Cambridge, England, Cambridge University Press, 1999.