Estrogen exposure during gestation and risk of testicular cancer.

In this case--control study of 108 cases of testicular cancer in men under 30 years of age, cryptorchidism was a major risk factor [relative risk (RR) = 9.0]. Low birth weight was also associated with increased risk (RR = 3.2). Having severe acne at puberty was protective (RR = 0.37). Interviews with mothers of cases revealed that exposure of the mother to exogenous estrogen during pregnancy created a significant risk in the son (RR = 8.0). In first pregnancies, excessive nausea indicated an increased risk of testicular cancer (RR = 4.2). Increased body weight in the mother also increased the risk. The relation between these factors and testicular hypoplasia is discussed. Severe perimenopausal menorrhagia was a factor in the mother associated with reduced risk of testicular cancer in the son (RR = 0.10). A modified hormonal milieu in the mother appears to be important in the later development of testicular cancer in her sons.

Higher maternal levels of free estradiol in first compared to second pregnancy: early gestational differences.

Serum samples drawn from 34 women in the early part of both their first and their second pregnancies were assayed for estradiol (E2), percentage of free E2, and sex hormone-binding globulin-binding capacity (SHBG-bc). Subjects were participants in the Collaborative Perinatal Study conducted by the National Institute of Neurological and Communicative Disorders and Stroke (Bethesda, MD) to evaluate factors related to adverse pregnancy outcome. All pregnancies were full term, and no offspring had a congenital malformation. After adjustment for week of pregnancy, the percentage of free E2 was 9% higher (two-sided P = .007) and the amount of free E2 was 17% higher (two-sided P = .03) in first-pregnancy sera. Total E2 was also 7% higher in first-pregnancy sera after adjustment for week of pregnancy; SHBG-bc was 7% lower after adjustment for week of pregnancy and 9% lower after simultaneous adjustment for week of pregnancy and weight at the start of pregnancy; but these differences were not statistically significant. These findings confirm our previously published hypothesis that the early part of a woman's first pregnancy differs endocrinologically from her second and may provide further insight into pregnancy-related risk factors for testis cancer and cryptorchidism and into the protection afforded by first full-term pregnancy against breast cancer.

Maternal and gestational factors affecting the risk of cryptorchidism and inguinal hernia.

Case-control studies of cryptorchidism and inguinal hernia were undertaken on white males born within the cohort of the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. Significantly elevated risks of cryptorchidism were found for low birthweight, for a high maternal Quetelet's index and for oestrogens administered during gestation (R = 2.8). Similarly, in the case of inguinal hernia, significantly increased risk ratios were observed for low birthweight, for gestational use of progestins (RR = 2.1), and for breech labour (RR = 2.3). Because these malformations and testis cancer share many of the same risk factors, a common mechanism for production of these diseases is proposed which is mediated by testicular hypoplasia induced by excess exogenous or endogenous oestrogen in the mother.

Cryptorchidism, and epidemiologic study with emphasis on the relationship to central nervous system dysfunction.

This case-control study examines the relation of cryptorchidism to central nervous system dysfunction. Elevated odd ratios were found for cerebral palsy (RR = 34), low IQ (RR = 2.7), and low motor function measured by the Bayley test (RR = 3.6). Low IQ and cerebral palsy were independent risk factors for cryptorchidism. Breech labor (RR = 2.6), a gestation less than 34 weeks (RR = 2.0), and being a twin (RR = 4.1) were also independent risks. Other risk factors were estrogen use by the mother (RR = 3.3) and a maternal Quetelet index less than 24 (RR = 1.6). All of these risks were statistically significant. These factors suggest that cryptorchidism may be caused either by sex steroid action directly on the testes or by CNS damage, which in turn causes suppression of pituitary gonadotropins. The increased occurrence of cryptorchidism in twins and small babies indicates that retarded general fetal development can be another mechanism for maldescent of the testes.

A proportional mortality study of the acting profession.

Proportional mortality of actors and actresses was studied because cancers of many sites have been linked to hair dyes and cosmetics of which actors have been frequent users. Death records (1950-1978) for 2,618 white male and 838 white female members of Actors Equity and the Screen Actors Guild were compared with the U.S. mortality rats. Among males, significantly elevated proportional mortality ratios (PMR) were found for suicide (1.58), cirrhosis of the liver (1.99), all malignancies (1.15), and cancers of the colon/rectum (1.32), pancreas (1.51), and testes (2.37). Colon/rectum and pancreas cancers were not significantly elevated by proportional cancer mortality. Among females, significantly elevated PMRs were found for suicide (2.02) and lung cancer (2.20). Suicide in either sex was much more common in California than in New York. The elevated lung cancer in females was confined to Equity members. No elevations were found for cancers that have been related to hair dye or cosmetic use--ie, breast, ovary, bladder, leukemia, and lymphomas.

Hyperemesis gravidarum in relation to estradiol levels, pregnancy outcome, and other maternal factors: a seroepidemiologic study.

Two studies were conducted to assess factors associated with increased risk of hyperemesis gravidarum during pregnancy with data and serum samples collected from participants in the Collaborative Perinatal Study. In the case-control study, 419 pregnant women with hyperemesis gravidarum were matched on medical center, date of study registration, and race with 836 pregnant women who did not vomit during the index pregnancy. Younger age, nulliparity, and high body weight were significantly associated with increased risk of hyperemesis. Women with hyperemesis had significantly reduced risk of fetal loss; however, their infants had higher risk of central nervous system malformations. In the second study, first-trimester pregnancy hormones were measured in the serum of 35 women with hyperemesis and 35 control women who were individually matched to cases on age, parity, and medical center. After adjusting for length of gestation, mean levels of total estradiol were 26% higher and mean levels of sex hormone binding-globulin binding capacity were 37% higher in patients with hyperemesis gravidarum than in control subjects. These differences were statistically significant. Although human chorionic gonadotropin concentrations were higher in control pregnancies, the differences were not statistically significant. The average amount of estradiol that was nonprotein bound (adjusted for length of gestation) was also higher in patients than in control subjects. These results are consistent with the hypothesis that elevated estrogen levels are responsible for excessive vomiting in pregnancy.

Maternal hormone levels in early gestation of cryptorchid males: a case-control study.

A case-control study was conducted to assess maternal hormonal factors associated with increased risk of bearing a cryptorchid son. Serum samples were collected during the first trimester of pregnancy from participants in the US Collaborative Perinatal Study. Twenty-five mothers of normal offspring (controls) were individually matched on medical center, age, parity, weight and length of gestation at the time of sampling to women bearing sons who had a diagnosis of cryptorchidism at one year of age or older. Compared with controls, mothers of cryptorchid sons (cases) had significantly greater percentages of non-protein bound (P = 0.010) and albumin-bound (P = 0.014) estradiol during the first trimester of the index pregnancy. On average, cases had 16% more bioavailable oestradiol than controls. Levels of human chorionic gonadotropin, testosterone, non-protein bound testosterone and sex-hormone binding globulin did not differ between the two groups. The data presented support the hypothesis that cryptorchidism results from elevated maternal oestrogen levels early in pregnancy.

Cigarette smoking in pregnancy results in marked decrease in maternal hCG and oestradiol levels.

We have examined serum levels of oestradiol (E2), sex-hormone binding globulin (SHBG) and human chorionic gonadotrophin (hCG) during early pregnancy in relation to smoking status at the time of sampling in a series of 147 women. Smoking was associated with significantly depressed serum levels of E2, SHBG and hCG: in smokers, E2 levels were on average 17.6% lower (P = 0.037), SHBG levels were 12.4% lower (P = 0.15), and hCG levels were 21.5% lower (P = 0.044). There appeared to be a steady decline in these values with increasing cigarette consumption. These lower hormone levels in smokers may explain certain adverse effects of smoking in pregnancy.