How We Do It

The evolution and future of human reproduction

Spectators on Steroids

Hormone mimics disrupt human reproduction: Spotlight on BPA

My two previous blog pieces assessed evidence that human sperm counts are declining. Many environmental factors may disrupt our reproduction. Here, I focus on chemicals that mimic steroid hormones.

Dangers of Synthetic Products

It has only recently been recognized that chemicals in widely used synthetic products may threaten reproductive health. A prominent example is bisphenol A (BPA), an organic compound used in polycarbonate plastics, epoxy resins, and many other everyday items such as DVDs, sunglasses, medical devices, and automobile parts. Heat-resistant polycarbonate plastics are widely used to package food and drink, while the insides of cans and water pipes are coated with epoxy resins. BPA ranks among the top 50 chemicals now produced. Global annual production exceeded 5 million tons by 2008. It is routinely detected in human blood and urine in industrialized countries.

One of the first issues to arouse concern was use of bottles containing BPA to feed infants. It is particularly alarming that, compared to adults, exposure to BPA is doubled for children generally and ten times greater for babies in intensive care units. In one notable experiment in which 77 Harvard student volunteers drank cold liquids from polycarbonate bottles for just one week, urinary levels of BPA rose by over two thirds. After many years of declaring BPA to be safe, in 2012 the Food and Drug Administration at last banned its use in baby bottles and sippy cups.

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From Sperm Counts to Till Receipts

In 2010, a Chinese/American team led by reproductive epidemiologist De-Kun Li examined self-reported sexual problems in male factory workers in China, some exposed to exceedingly high BPA levels, others without exposure. After carefully excluding potential confounding factors, the team found that problems were consistently 4-7 times more likely in workers exposed to BPA. Deficiencies spanned every domain of male sexuality: desire, erection, ejaculation, and satisfaction. Moreover, risk increased with cumulative exposure. But factory exposure to BPA was extreme; levels in urine samples were some 50 times higher than in controls.

A year later, the same research group reported results from a follow-up study that directly compared semen quality with urinary BPA levels. Over 200 men with and without workplace exposure to BPA were studied in four regions of China. After excluding confounding effects, elevated urinary BPA was significantly associated with decreased semen quality. The risk was more than doubled for lower sperm motility, more than tripled for decreased sperm concentration and vitality, and more than quadrupled for lower sperm counts. These results provided the first tangible evidence that BPA adversely affects semen quality.

Attention has mainly focused on BPA ingested through food or drink containers, but it also readily passes through skin. Therein lies the rub. BPA is often present on paper receipts printed with lightweight devices using a thermal transfer process. A powdery layer of BPA is commonly used to coat one side. Such receipts have been increasingly used in cash registers and ATMs since the 1970s, becoming a major contaminant of recycled paper. In 2010, large-scale testing commissioned by the US Environmental Working Group identified high levels of BPA on 40% of receipts sampled from major commercial sources. Total amounts detected were up to a thousand times greater than with other, more widely discussed sources of exposure, such as plastic bottles and food cans. Monitoring by the US Centers for Disease Control revealed that on average salespeople carried 30% more BPA in their bodies than other adults.

A Dubious Past

Alarm bells should have been ringing since the 1930s, when BPA was experimentally tested on female rats with their ovaries surgically removed. At the time, it was held that any substance needs a core structure of four carbon rings to behave like a steroid hormone. However, in two papers published in 1936 and 1938, biochemists Edward Dodds and Wilfrid Lawson found that BPA and several related compounds act like estrogens despite having only two carbon rings. When fed to female rats lacking ovaries, any of these compounds affected the vaginal lining in the same way as estrogens.

But industrial users argue that BPA is unlikely to pose a significant health risk as it is many thousand times less potent than natural estrogens and is rapidly eliminated from the body. The website of the Polycarbonate/BPA Global Group of the American Chemistry Council indicates that BPA is entirely safe. In 2008, the Food and Drug Administration reached the same conclusion; but Congress sensibly took steps to restrict use of BPA and asked the FDA to reconsider. Several authorities have recognized the potential toxic effects of BPA, at least in baby bottles, for instance in the European Union and Canada. In 2010, Canada became the first country to recognize BPA officially as a toxic substance. One thing is certain: Everyone in industrialized nations is exposed to BPA every day. For most national governments, the jury is still out; but the evidence urgently needs unbiased appraisal.

 

Readers are encouraged to visit the website of The Endocrine Disruption Exchange (TEDX: http://www.endocrinedisruption.com/home.php) and to watch an excellent video by its Founder, Dr. Theo Colborn, discussing the general problem of endocrine disruptors in the environment.

My book, How We Do It, is out today, June 11. You can purchase it here.

 

References

Carwile, J.L., Luu, H.T., Bassett, L.S., Driscoll, D.A., Yuan, C., Chang, J.Y., Ye, X.Y., Calafat, A.M. & Michels, K.B. (2009) Polycarbonate bottle use and urinary bisphenol A concentrations. Environmental Health Perspectives 117:1368-1372.

Colborn, T., Dumanoski, D. & Myers, J.P. (1996) Our Stolen Future: Are We Threatening our Fertility, Intelligence and Survival? New York: Dutton.

Dodds, E.C. & Lawson, W. (1936) Synthetic estrogenic agents without the phenanthrene nucleus. Nature 137:996.

Dodds, E.C. & Lawson, W. (1938) Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus. Proceedings of the Royal Society of London B 125:222-232.

Li, D.-K., Zhou, Z.-J., Miao, M., He, Y., Wang, J.-T., Ferber, J., Herrinton, L.J., Gao, E.-S. & Yuan, W. (2011) Urine bisphenol-A (BPA) level in relation to semen quality. Fertility & Sterility 95:625-630.

Li, D.-K., Zhou, Z.-J, Qing, D., He, Y., Wu, T., Miao, M., Wang, J.-T, Weng, X., Ferber, J.R., Herrinton, L.J., Zhu, Q., Gao, E.-S., Checkoway, H. & Yuan, W. (2010) Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction. Human Reproduction 25:519-527.

Vandenberg, L.N., Chahoud, I., Heindel, J.J., Padmanabhan, V., Paumgartten, F.J.R. & Schoenfelder, G. (2010) Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environmental Health Perspecives. 118:1055-1070.

Robert Martin, Ph.D., is the A. Watson Armour III Curator of Biological Anthropology at the Field Museum in Chicago.

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