Maternal Hormone Levels and Perinatal Characteristics: Implications for Testicular Cancer
Introduction
There is increasing evidence that testicular germ cell tumors (TGCTs) originate in utero (1). Although the mechanism that increases risk is unknown, it was suggested that an imbalanced intrauterine hormonal milieu may be important 2, 3, 4. However, it is very difficult to study the association between a fetal exposure that is not routinely measured, such as hormone levels, and a disease that occurs decades later. To overcome this problem, some studies examined the relationship between perinatal variables and TGCT under the assumption that perinatal variables are good surrogate measures of in utero hormonal conditions.
To test the validity of this assumption, several studies examined relationships between perinatal factors and maternal hormone levels 5, 6, 7, 8, 9, 10, 11. However, some of these studies included hormone samples from only one time in pregnancy or studied members of only one ethnic group. In addition, almost all studies to date included mothers pregnant with both male and female fetuses. Because relationships between perinatal factors and maternal hormones may vary by sex of the fetus or by ethnic group, further scrutiny of these relationships was indicated.
With the goal of informing future studies of TGCTs, relationships between perinatal factors and maternal hormone levels were examined in mothers pregnant with male fetuses. The mothers were selected to represent populations at differing risks for TGCT, white Americans (high risk) and black Americans (low risk), to determine whether perinatal factor–hormone relationships vary by ethnicity. In addition, relationships were examined in samples drawn in the first and third trimesters because these are critical periods for testicular descent, the failure of which is associated strongly with risk for TGCTs (12).
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Study Population
A detailed description of the study population was reported previously (13). Briefly, 150 pairs of black and white mothers were selected from participants of the Collaborative Perinatal Project (CPP). The CPP cohort study was designed to examine perinatal risk factors for neurologic disorders in offspring (14). Pregnant women were enrolled at 12 medical centers in 11 US cities (Baltimore, Boston, Buffalo, Memphis, Minneapolis, New Orleans, New York (two centers), Philadelphia, Portland,
Results
Black mothers were significantly more likely than white mothers to be younger (p < 0.0001), be of lower social economic status (p < 0.0001), and have low-birth-weight sons (p = 0.02; Table 1). No other significant differences were observed.
As previously reported (13), black mothers had significantly higher levels of estradiol (p = 0.05) and testosterone (p ≤ 0.01) in first-trimester samples, but had significantly lower estradiol-testosterone and estriol-testosterone ratios (p = 0.01).
Discussion
Stimulated by racial differences in cancer risk, several studies compared hormone levels in black and white mothers 9, 13, 21. Findings of greater testosterone levels in black mothers led to the hypothesis that lower risk for TGCTs in black men may be caused by greater maternal testosterone levels (21). Alternatively, several TGCT studies hypothesized that increased risks associated with such factors as hyperemesis gravidarum (22) and low birth order (15) may link greater maternal estrogen
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This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, National Institute of Environmental Health Sciences, and National Institute of Child Health and Human Development.