The urinary estrogen theory. Part II

In my last post, I argued that large quantities of estrogen were flushed into lakes and rivers across North America and northern Europe between the introduction of modern sewer systems in the late 19th century and the shift to secondary and tertiary sewage treatment after the 1960s. By separating out solid fecal waste and rapidly discharging the fluid component into nearby cold bodies of water, we unwittingly created ideal conditions for the preservation of urinary estrogen, which then came back to us via water for drinking and bathing.

Did this estrogen affect the sexual development of young boys? It probably had few effects prenatally. For one thing, there is the placental barrier. For another, the developing human fetus is already adapted to the high levels of estrogen in the mother’s body.

But there may have been effects outside the womb. The human infant is adapted to external environments that have very little urinary estrogen. Until the late 1800s, urine was discharged into warm aqueous media with plenty of organic matter, e.g., privies, cesspools, ditch sewers … or the nearest bushes. Any estrogen would have been quickly biodegraded by nitrifying bacteria. All of this changed, however, with the advent of modern sewer systems and the ensuing estrogen contamination of the public water supply.

For this period (late 1800s – 1970s), we have no direct data on estrogen levels in the environment. Indirect evidence, however, is provided by male reproductive illnesses that are linked to estrogenic exposure, notably lower sperm counts and higher rates of testicular cancer, cryptorchidism, and hypospadias (Carlsen et al., 1992; Carlsen et al., 1995; Colborn et al., 1996; Klotz, 1999; Sharpe, 1998). These illnesses arise from impeded development of Sertoli cells that eventually produce spermatozoa in adult males. In particular, the impediment seems to happen while these cells are dividing and replicating during the fetal stage or infancy, although some replication also occurs during early puberty (Sharpe, 1998).

Prior to 1940, we have reliable data only on testicular cancer—an important consideration if we wish to distinguish between post-late-1800s exposure to urinary estrogen and post-1940s exposure to synthetic estrogenic compounds (Colborn et al., 1996). In the United States, the Connecticut Tumor Registry (CTR) gives the incidence of testicular cancer as far back as 1935 and victim birth cohorts as far back as 1910 (Brown et al., 1986; Schottenfeld et al., 1980). Birth cohorts are more informative than year of tumor diagnosis because testicular cancer seems to originate early in life (Bergström et al., 1996; Brown et al., 1986; Østerlind, 1986). Outside the U.S., long‑running registries have been kept in England and Wales and in other northern European countries (Adami, et al., 1994; Bergström et al., 1996; Davies, 1981; Østerlind, 1986).

The CTR shows a steadily increasing incidence of testicular cancer since the earliest cohort of men born in 1910‑14 (Brown et al., 1986; Schottenfeld et al., 1980). The registry for England and Wales goes further back and reveals that the increase began among men born in 1891‑1900 (Davies, 1981). Registries in northern Europe (Denmark, Norway, Sweden, former East Germany, Finland, and Poland) show an absence of decade-to-decade change in cohorts born between 1880 and 1920, followed by a steady increase in later cohorts (Bergström et al., 1996). In North America and northern Europe, then, the increase seems to predate the post‑1940s entry of synthetic estrogenic compounds into the environment. It is also worth noting that exposure to industrial estrogenic chemicals has been worse in Poland and the former East Germany than in Denmark and Norway, yet the latter countries have much higher incidences of testicular cancer (Adami et al., 1994).

Thus, over the 20th century, the rising incidence of testicular cancer seems to track the growing volume of untreated wastewater if we allow a mean time lag of 35 years between the initial cancer‑inducing event and tumor development [1]. Given the marked decline in untreated wastewater following the 1972 Clean Water Act in the U.S. and similar efforts in other countries, should we now be seeing a parallel decline in the incidence of testicular cancer?

There has in fact been a plateauing of U.S. incidence rates since the 1990s (Holmes et al., 2008; Pharris‑Ciurej, 1999). A similar leveling off has been noted in England and Wales among men born since 1960 and in Scotland among men born since 1965 (Dos Santos, et al., 1999; Swerdlow et al., 1998; see also Cancer Research UK). Denmark has reported a leveling off in post-1963 cohorts and even a decrease in the 1968 cohort, although incidence rates are still rising in the other Nordic countries (Jacobsen et al., 2006; Møller, 2001).

In addition to the plateauing of recent age cohorts, testicular cancer is much less common among men born during World War II in Denmark and, to a lesser extent, in Norway and Sweden (Jacobsen et al., 2006; Møller, 2001). The reason is still a mystery, all the more so because these countries were largely spared the horrors of WWII.

It does seem, then, that the incidence of testicular cancer mirrors rising and falling levels of urinary estrogen in the environment. In my next post, I will return to the possibility of a correlation with changes to male sexual orientation, particularly in terms of search image and desired self-image.

Note

[1]. Although testicular cancer can occur in teenagers, it is much more common in adulthood. “Unlike most other cancers, testicular cancer, with a peak incidence in the third decade of life, suggests a latency period that involves some pre or postnatal stimulatory event that influences subsequent tumor development. The widespread observation of a birth cohort correlation for testicular cancer suggests that early or prolonged exposure to some carcinogenic stimuli might be required for the subsequent development of testicular cancer.” (McKiernan et al., 2000)

References

Adami, H‑O., Bergström, R., Möhner, M., Zatonski, W., Storm, H., Ekbom, A., Tretli, S., Teppo, L. Ziegler, H., Rahu, M., Gurevicius, R., and Stengrevics, A. (1994). Testicular cancer in nine northern European countries. Int. J. Cancer, 59, 33‑38.

Bergström, R., Adami, H‑O., Möhner, M., Zatonski, W., Storm, H., Ekbom, A., Tretli, S., Teppo, L., Akre, O., and Hakulinen, T. (1996). Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J. Natl. Cancer Inst., 88, 727‑733.

Brown, L.M., Pottern, L.M., Hoover, R.N., Devesa, S.S., Aselton, P., and Flannery, J.T. (1986). Testicular cancer in the United States: trends in incidence and mortality. Int. J. Epidemiol., 15, 164‑170.

Carlsen, E., Giwercman, A., Keiding, N., and Skakkebaek, N.E. (1995). Declining semen quality and increasing incidence of testicular cancer: is there a common cause? Environ. Health Perspect., 103(suppl. 7), 137‑139.

Carlsen, E., Giwercman, A., Keiding, N., and Skakkebaek, N.E. (1992). Evidence for decreasing quality of semen during past 50 years. BMJ, 305, 609‑13.

Colborn, T., Dumanoski, D., and Peterson Myers, J. (1996). Our stolen future. New York: Dutton.

Davies, J.M. (1981). Testicular cancer in England and Wales: some epidemiological aspects. Lancet, 1, 928‑32.

Dos Santos Silva, I., Swerdlow, A.J., Stiller, C.A., and Reid, A. (1999). Incidence of testicular germ-cell malignancies in England and Wales: Trends in children compared with adults. Int. J. Cancer, 83, 630-634.

Holmes, L. Jr., Escalante, C., Garrison, O., Foldi, BX., Ogungbade, G.O., Essien, E.J., and Ward, D. (2008). Testicular cancer incidence trends in the USA (1975-2004) : Plateau or shifting racial paradigm? Public Health, 122(9), 862-872.

Jacobsen, R., Møller, H., Thoresen, S.Ø., Pukkala, E., Kruger Kjaer, S., and Johansen, C. (2006). Trends in testicular cancer incidence in the Nordic countries, focusing on the recent decrease in Denmark. International Journal of Andrology, 29, 199-204.

Klotz, L.H. (1999). Why is the rate of testicular cancer increasing? CMAJ, 160, 213-4.

McKiernan, J.M., Hensle, T.W., and Fisch, H. (2000). Increasing risk of developing testicular cancer by birth cohort in the United States, Dialogues in Pediatric Urology, 23, 7-8.

Møller, H. (2001). Trends in incidence of testicular cancer and prostate cancer in Denmark. Human Reproduction, 16, 1007-1011.

Østerlind, A. (1986). Diverging trends in incidence and mortality of testicular cancer in Denmark, 1943‑1982. Br. J. Cancer, 53, 501‑5.

Pharris‑Ciurej, N.D., Cook, L.S., and Weiss, N.S. (1999). Incidence of testicular cancer in the United States: has the epidemic begun to abate? Am. J. Epidemiol., 150, 45‑6.

Schottenfeld, D., Warshauer, M.E., Sherlock, S., Zauber, A.G., Leder, M., and Payne, R. (1980). The epidemiology of testicular cancer in young adults. Am. J. Epidemiol., 112, 232‑246.

Sharpe, R.M. (1998). Natural and anthropogenic environmental oestrogens: the scientific basis for risk assessment. Environmental oestrogens and male infertility. Pure & Appl. Chem., 70, 1685‑1701.

Surveillance, Epidemiology, and End Results (SEER) Program Public‑Use Data (1973­-1998), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch,

Swerdlow, A.J., Dos Santos Silva, I., Reid, A., Qiao, Z., Brewster, D.H., and Arrundale, J. (1998). Trends in cancer incidence and mortality in Scotland: description and possible explanations. Br. J. Cancer, 77(supplement 3), 1-16.