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Weir, HK, LD Marrett, N Kreiger, GA Darlington and L Sugar. 2000. Pre-natal and peri-natal exposures and risk of testicular germ cell cancers. International Journal of Cancer 87:438-443.

Weir et al. examine the association between exposure to hormones during fetal development--both maternal and exogenous--and the risk of testicular germ-cell cancer. They found that "exogenous hormone exposure was associated with elevated risk." They also found that "exposure to maternal hormones, particularly estrogens, is associated with testicular germ-cell cancer risk.

"Not only does exposure to elevated levels (exogenous hormone use, pre-term birth, and first birth among young mothers) increase risk, but also exposure to relatively lower levels (heavy cigarette consumption, and perhaps, bleeding and threatened miscarriage) may decrease cancer risk."

What did they do?
Weir et al. conducted a population-based, case-control study that focused on all confirmed cases of primary malignant germ-cell testicular cancer occurring in Ontario residents aged 16-59 between 1 January 1987 and 31 December 1989. Controls in the study were a population-based random sample of men between aged 16-59.

Weir et al. confirmed the diagnosis of testicular cancer by examining samples from pathology labs, and then gathered data on risk facters through use of a self-administered questionnaire sent to the mothers by the study subjects. Mothers were also interviewed by phone.

Of 621 eligible cases, 502 (80.8%) completed a mailed questionnaire. Questionnaires were also sent to 1,438 controls, of which 67.8% participated by returning a completed form.

"Exogenous hormone exposure was determined from the mother's reported use of prescription hormones (e.g., diethylstilbestrol or premarin), prescription medication for conditions associated with threatened miscarriage, injections or pills to determine pregnancy, and use of oral contraceptives around the time of conception."

What did they find?
Weir et al. found that more cases than controls reported exposure to exogenous hormones. The odds ratio for this risk factor was 4.9, with the 95% confidence interval running from 1.7 to 13.9. Thus the association was highly significant statistically.

"Our results support the hypothesis that exposure to maternal hormones, particularly estrogen, is associated with testicular germ-cell cancer risk. Not only does exposure to elevated levels of maternal hormones (exogenous hormone use and pre-term birth) appear to increase cancer risk, but exposure to relatively lower levels of maternal hormones (heavy cigarette consumption, and, perhaps, bleeding and threatened miscarriage), , but as measured by indices of exposure to maternal hormones, appears to decrease cancer risk."

The strength of the conclusions reached by Weir et al. are limited by several factors. Two factors stand out: (1) restrospective questionnaires that, in this case, attempt to reconstruct details of medical history that occurred decades in the past are notoriously weak and sometimes provide inaccurate data. (2) the questionnaire asked about only a small number of sources of exogenous hormones, all prescription drugs, that could have been involved. No information was available about contamination as a source.

What does this mean?
These are intriguing results that build upon a previous literature suggesting (with both positive [e.g., Depue et al. 1983] and negative [e.g., Brown et al. 1986] results) that exogenous hormones may play a role in testicular cancer.

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