Tag: 1992

Occurrence of tumours in the descendants of CBA male mice prenatally treated with diethylstilbestrol

Statistically significant increased incidence of tumours observed in females

DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced for consumption.

1992 Study Abstract

There is well documented evidence both in humans and in experimental animals that exposure to diethylstilbestrol (DES) during pregnancy results in an increased incidence of tumours in the progeny. The increased cancer risk has been reported to persist in the second generation descendants of DES-exposed pregnant mice. In the present experiment, female mice of the CBA strain were treated at day 17 of pregnancy with 1 microgram/g body weight of DES. The descendants of DES-treated mothers, described as F1DES, were mated among each other or with untreated animals. The F1DES females were found to be sterile when mated with either F1DES or untreated males. F1DES males were successfully mated with untreated females. In the female offspring so obtained, but not in the male, a statistically significant increased incidence of tumours was observed, in particular of uterine sarcomas, and also of benign ovarian tumours and of lymphomas.

Sources and more information
  • Occurrence of tumours in the descendants of CBA male mice prenatally treated with diethylstilbestrol, International journal of cancer, NCBI PMID: 1728603, 1992 Jan 2.
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DES exposure linked to reduced hemispheric laterality and lowered spatial ability in males

Hormones and behavior, Volume 26, Issue 1, Pages 62–75, March 1992

Cognitive-Dissonance image
This 1992 study provides direct evidence of a relationship between brain laterality, spatial cognitive ability, and prenatal exposure to hormones in human males. Cognitive Dissonance image by Jon Haynes Photography.

1992 Study Abstract

Ten males exposed to Diethylstilbestrol (DES), a nonsteroidal synthetic estrogen, during gestation were compared to their matched, unexposed brothers on measures of brain hemispheric specialization for processing nonlinguistic spatial information and cognitive abilities.

DES exposure was associated with reduced hemispheric laterality and lowered spatial ability.

These data provide direct evidence of a relationship between brain laterality, spatial cognitive ability, and prenatal exposure to hormones in human males. Further, the implications of these findings for understanding sexual differentiation of the human brain are discussed.

Sources
  • Effects of prenatal exposure to diethylstilbestrol (DES) on hemispheric laterality and spatial ability in human males, Reinisch JM1, Sanders SA., Horm Behav. NCBI PMID: 1563729, 1992 Mar;26(1):62-75. Full study doi:10.1016/0018-506X(92)90032-Q.
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Prenatal diethylstilbestrol exposure and performance on college entrance examinations

DES exposure and written tests performance

writing-test
No differences in test performance were seen among exposed daughters. Among sons, test scores were marginally higher among the exposed, probably due to chance. Written test image by Melanie Holtsman.

1992 Study Abstract

The fetal rodent brain is permanently altered by exposure to sex hormones. Long-term effects of prenatal sex hormones on the human brain are far less clear.

In order to explore such effects, we studied a measure of cognitive function among young adults who had been exposed in utero to a powerful synthetic estrogen. In a randomized clinical trial conducted at the University of Chicago in 1950-1952, 1646 pregnant women were randomly assigned to receive either high doses of Diethylstilbestrol or placebo.

Women in this study gave birth to 1653 liveborn infants, of whom 1603 (820 sons and 783 daughters) survived to their fifteenth birthday. College entrance examination scores were obtained for 42% of these offspring. No differences in test performance were seen among exposed daughters. Among sons, test scores were marginally higher among the exposed, probably due to chance.

Sources
  • Prenatal diethylstilbestrol exposure and performance on college entrance examinations, Wilcox AJ, Maxey J, Herbst AL, NCBI PMID: 1398561, Horm Behav. 1992 Sep;26(3):433-9. Full study.
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Diethylstilboestrol: Pharmacology, Toxicology and Carcinogenicity in Experimental Animals

Some experimental evidence points to the possibility of a transgenerational carcinogenic effect after prenatal exposure to Diethylstilbestrol

Abstract

image of PubMed NCBI The Endocrine Society logo
Some experimental evidence points to the possibility of a transgenerational carcinogenic effect after prenatal exposure to Diethylstilbestrol.

Diethylstilboestrol (DES) exerts several toxic effects in experimental animals, by mechanisms which are still unclear. The genotoxicity of the drug has been attributed to a quinone metabolite and is mainly clastogenic, including sister chromatid exchange, unscheduled DNA synthesis, chromosomal aberrations, disruption of mitotic spindle and aneuploidy. There is evidence that genotoxic effects may occur also transplacentally. Intrauterine and early postnatal exposure to DES can cause a variety of dysplasias. In the offspring of female mice exposed to DES during pregnancy, histological changes are observed in the vaginal and cervical epithelium, the endometrium, the ovary, the testis and the epididymis. Prenatal exposure of rats to DES led to decreased litter size and to urethrovaginal cloaca, penile and testicular hypoplasia, and cryptorchidism. Vaginal ridging, vaginal adenosis, testicular hypoplasia and cryptorchidism have been observed in rhesus monkeys following prenatal exposure. There is sufficient evidence that diethylstilboestrol is carcinogenic in experimental animals, after either prenatal or postnatal exposure. Mice show a similar type of carcinogenicity to that observed in humans, target organs being vagina, cervix, uterus, ovary, mammary gland and testis. In rats, prenatal exposure to DES produces mostly mammary and pituitary tumours, but also some tumours of the vagina. Hamsters develop tumours of vagina, cervix, endometrium, epididymis, testis, liver and kidney. DES induces ovarian papillary carcinomas in dogs, and malignant uterine mesotheliomas in squirrel monkeys. Some experimental evidence points to the possibility of a transgenerational carcinogenic effect, since prenatal treatment of mice with DES is followed by an increased incidence of uterine and ovarian carcinomas in the second-generation descendants.
Experimental results could have been used to predict the adverse effects of DES observed in humans in the early 1970s: DES had been reported to be carcinogenic in mice in the 1930s, while experiments in the 1960s had provided evidence that exposure during pregnancy could result in an increased cancer risk in the progeny.

Sources:
  • Diethylstilboestrol: II, pharmacology, toxicology and carcinogenicity in experimental animals,
    NCBI, PMD: 1445734, Eur J Cancer. 1992;29A(1):149-55.
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Worse than the Disease: Pitfalls of Medical Progress

DES and the Elusive Goal of Drug Safety

Worse than the Disease - Pitfalls of Medical Progress book cover
Includes “DES and the elusive goal of drug safety” case study

Synopsis:
The distance between medical and public priorities is exposed in four case studies that reveal the human choices governing scientific innnovation and explore the political, economic and social factors influencing those choices.

Description
This book – by Diana Barbara Dutton – examines four medical innovations that epitomize the pitfalls of progress:

  • DES and the elusive goal of drug safety – about a synthetic estrogen prescribed to millions of women to supposedly prevent miscarriages, which produced devastating side effects;
  • the artificial heart;
  • the 1976 swine flu immunization programme;
  • genetic engineering: science and social responsibility.

Dutton and the contributors trace the human choices that govern medical and scientific innovation and explore the political, economic, and social factors that influence those choices. In the process, they reveal a deep gulf between the priorities of medical innovation and the concerns of the general public. They then propose concrete policy changes to help bridge that gulf.

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