Play behavior affected by early administration of diethylstilbestrol during development

EDCs are able to influence the development of the brain during a critical period, resulting in long-term effects on behavior

2005 Study Abstract

Play behavior is affected by alteration of the hormonal environment during development. In fact, congenital adrenal hyperplasia or early administration of diethylstilbestrol are able to modify female play behavior in mammals.

Early exposure to a low dose of bisphenol A affects socio-sexual behavior of juvenile female rats, US National Library of Medicine National Institutes of Health, Brain research bulletin, NCBI PubMed, PMID: 15811590, 2005 Apr.

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In this research, play behavior of female rats was used to explore the effects of perinatal exposure to low, environmentally relevant dose of bisphenol A (BPA), a xenoestrogen widely diffused in the environment.

We used 18 females born to mothers exposed to 40 microg/kg/day BPA during pregnancy and lactation, and 18 control females. The subjects were observed in a heterosexual social situation from 35 to 55 days of age.

Six main behaviors were identified by principal component analysis (PCA): exploration, defensive behavior to males, play behavior with males, play behavior with females, low-intensity mating behavior, social grooming. Early administration of BPA was responsible for a significant increase of exploration (including social investigation) (p<0.001), as well as a decrease of play with males (p<0.02) and social grooming (p<0.01) at 45 days of age, indicating a general decrease of playful interactions.

In general our results suggest that BPA does not induce a clear masculinization of female behavior, but is able however to defeminize some aspects of female behavior. This result is compatible with the estrogenic properties of BPA, and suggests caution in the use of a chemical that, in the range of human exposure, is able to influence the development of the brain during a critical period, resulting in long-term effects on behavior.

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Psychosexual characteristics of men and women exposed prenatally to DES

DES Follow-up Study

Animal studies suggest that estrogen affects the developing brain, including the part that governs sexual behavior and right and left dominance. We examined the potential impact of prenatal DES exposure on these characteristics in 2,684 men and 5,686 women participating in the NCI DES Follow-up Study.

DES Follow-up Study, National Cancer Institute, bibliography_Psychosexual_summary, 2003.

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Information on marital status, sexual behavior, and handedness was reported by subjects on a questionnaire. Responses indicated that DES neither influenced sexual behavior nor resulted in an increased likelihood of homosexual contact. In sons, DES was unrelated to the likelihood of ever having been married or of having a same-sex sexual partner in adulthood, age at first intercourse and number of sexual partners. DES Daughters were slightly more likely than unexposed women to have ever been married but were less likely to report having had a same-sex sexual partner, having had their first sexual intercourse before age 17 and to having had more than one sexual partner.

DES Daughters were just as likely as unexposed women to be left-handed. DES Sons were slightly more likely to be left-handed than unexposed men. Overall, about 17% of women reported a mental illness, but we found no evidence that it was more frequent in the exposed than the unexposed women. Mental illness was not assessed in the men.

2003 Study Abstract

Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol, US National Library of Medicine, Epidemiology, NCBI PubMed PMID: 12606880, 2003 Mar.

BACKGROUND
Between 1939 and the 1960s, the synthetic estrogen diethylstilbestrol (DES) was given to millions of pregnant women to prevent pregnancy complications and losses. The adverse effects of prenatal exposure on the genitourinary tract in men and the reproductive tract in women are well established, but the possible effects on psychosexual characteristics remain largely unknown.

METHODS
We evaluated DES exposure in relation to psychosexual outcomes in a cohort of 2,684 men and 5,686 women with documented exposure status.

RESULTS
In men, DES was unrelated to the likelihood of ever having been married, age at first intercourse, number of sexual partners, and having had a same-sex sexual partner in adulthood. DES-exposed women, compared with the unexposed, were slightly more likely to have ever married (odds ratio [OR] = 1.1; confidence interval [CI] = 1.0-1.4) and less likely to report having had a same-sex sexual partner (OR = 0.7; CI = 0.5-1.0). The DES-exposed women were less likely to have had first sexual intercourse before age 17 (OR = 0.7; CI = 0.6-0.9) or to have had more than one sexual partner (OR = 0.8; CI = 0.7-0.9). There was an excess of left-handedness in DES-exposed men (OR = 1.4; CI = 1.1-1.7) but not in DES-exposed women. DES exposure was unrelated to self-reported history of mental illness in women.

CONCLUSIONS
Overall, our findings provide little support for the hypothesis that prenatal exposure to DES influences the psychosexual characteristics of adult men and women.

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DES exposure : implications for health care providers

Why did DES Daughters develop an enduring distrust of the medical profession?

2000 Study Abstract

A focus group study of women exposed to diethylstilbestrol (DES) in utero (DES daughters) was conducted to gain understanding about exposure to this drug from a patient perspective.

A focus group study of DES daughters: implications for health care providers, US National Library of Medicine, Psycho-oncology, NCBI PubMed PMID: 11038482, 2000 Sep-Oct.

Image credit chinagrrrl.

Focus group participants reported that learning about their DES exposure was devastating; they experienced strains in their family relationships, emotional shock, a feeling that their health concerns were not appreciated by others and, to some degree, a sense of social isolation.

Although many were aware of the need for special gynecological exams and high-risk prenatal care, they were frustrated by what they felt was a lack of reliable and clear information about the effects of DES exposure.

Most expressed questions and anxiety about their health.

Many found their communication with physicians about their DES exposure unsatisfying. They felt that physicians lacked information about the long-term health effects of DES exposure and as a result did not give them accurate information. Furthermore, they felt that physicians were dismissive of their concerns and often gave what they felt to be false reassurances. Consequently, the women developed an enduring distrust of the medical profession.

The results of the study suggest implications for the delivery of health care to DES daughters.

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Language lateralization and handedness in DES-exposed women

Many DES Daughters more likely to be left handed for writing

2000 Study Abstract

Hand preferences and language lateralization were assessed in women exposed prenatally to the synthetic estrogen, diethylstilbestrol (DES), and in their unexposed sisters.

Language lateralization and handedness in women prenatally exposed to diethylstilbestrol (DES), US National Library of Medicine, Psychoneuroendocrinology, NCBI PubMed PMID: 10818283, 2000 Jul.

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The DES-exposed women showed an increased degree of hand preference (regardless of direction) and were more likely to be left handed for writing. However, the groups did not differ significantly on a dichotic listening measure of language lateralization.

Perhaps as a result of the alterations in hand preferences, the typical relationship between hand preferences and language lateralization was disrupted in the DES-exposed group. Also, within the DES-exposed group, exposure early in gestation correlated with left handedness whereas exposure late in gestation correlated with reduced left ear (right hemisphere) scores on the verbal dichotic task.

Results are discussed in terms of theoretical perspectives predicting hormonal influences on sexual differentiation of hemispheric asymmetry and in terms of separate critical periods for hormonal effects on individual sexually differentiated characteristics.

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DES-Mother and DES-Daughter Relationship

Exposure to DES may reveal pre-existing difficulties from generation to generation

1996 Study Abstract

The psychological consequences resulting from the exposure to diethylstilbestrol (DES), a non-steroidal oestrogen, on the mother-daughter relationship are studied using semi-directive interviews with 43 daughters and 7 mothers treated with DES during their pregnancies.

Prenatal exposure to diethylstilbestrol and the mother-daughter relationship, US National Library of Medicine, European journal of obstetrics, gynecology, and reproductive biology, NCBI PubMed PMID: 8730622, 1996 Apr.

These women referred to gynaecological consultation for DES-related problems.

The daughters, exposed to DES during their foetal life, learned about DES after a pregnancy mishap (35% of the cases), or by accident (65% of the cases).

All of them were shocked when the existence of DES and its side effects were revealed to them.

Consequences on the mother-daughter relationship were

  • absent in 60% of the cases,
  • favourable in 20%,
  • and negative in 20%.

Five percent of the women showed hostility towards the medical practice, but 65% were not suspicious of the drugs administered to them during their pregnancies. For 64% of them, administration of DES to their mother had been kept secret. In 7 out of 50 cases, parents alone came for medical assistance in order to manage the secret.

Exposure to DES may reveal pre-existing difficulties not only between the mother and the daughter, but sometimes beyond from generation to generation.

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Childhood play behavior and adult gender-role behavior in DES-exposed women

US National Library of Medicine, Archives of sexual behavior

1992 Study Abstract

Data from lower mammals suggest a masculinizing or defeminizing influence of pre- or perinatal diethylstilbestrol (DES) exposure on various aspects of the sex-dimorphic behavior (including juvenile rough-and-tumble play) of genetic females.

Prenatal exposure to diethylstilbestrol (DES): childhood play behavior and adult gender-role behavior in women, US National Library of Medicine, Archives of sexual behavior, NCBI PubMed PMID: 1417473, 1992 Oct.

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However, three previous studies on childhood play and adult gender-role behavior in human females have led to ambiguous results. In a follow-up study of 60 women with prenatal exposure to DES and 26 controls, we used psychometrically well-designed multi-item scales based on self-report inventories for the assessment of these aspects of behavior.

No effects of DES could be demonstrated. We conclude that, at the doses studied, prenatal DES exposure in human females has not led to behavioral masculinization or defeminization of childhood play and adult gender-role behavior.

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Understanding sexual differentiation of the human brain

DES exposure associated with reduced hemispheric laterality and lowered spatial ability

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.

Effects of prenatal exposure to diethylstilbestrol (DES) on hemispheric laterality and spatial ability in human males, US National Library of Medicine, Hormones and behavior, NCBI PubMed PMID: 1563729, 1992 Mar.

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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.

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Gender-related behavior in females following prenatal exposure to DES

Hormones and behavior, 1989

Study Abstract

Animal research has shown that diethylstilbestrol (DES) present during the sensitive developmental periods of the hypothalamus and adjacent areas of the brain affects the development of sex-dimorphic brain structures and subsequent behavior.

To test for corresponding behavioral effects in humans, 30 women with a history of prenatal DES exposure were contrasted with 30 unexposed women who had been referred to the same clinic for a colposcopic examination because of an abnormal Pap smear.

The development of gender-related behavior in females following prenatal exposure to diethylstilbestrol (DES), US National Library of Medicine, Hormones and behavior, NCBI PubMed PMID: 2606466, 1989 Dec.

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Gender-role behavior of childhood, adolescence, and adulthood was assessed by means of a semistructured interview, the Gender Role Assessment Schedule-Adult, and the Bem Sex Role Inventory. The mothers of these women were interviewed about their daughters with the “mother form” of the same interview schedule.

The results suggest that DES women show less orientation toward parenting than the controls. There were no consistent group differences in other domains of gender-role behavior.

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Depression and diethylstilbestrol exposure in women

image of depression in women

Major and recurrent depressions are likely to result from concern about reproductive and other gynecologic problems

1987 Study Abstract

Fifty women exposed to diethylstilbestrol (DES) in utero, 50 of their unexposed sisters (sister controls) and 43 women with abnormal Papanicolaou smears (population controls) were tested using the Diagnostic Interview Schedule to assess differences in depression and other kinds of psychologic impairment possibly associated with DES exposure.

Depression and diethylstilbestrol exposure in women, US National Library of Medicine, The Journal of Reproductive Medicine, NCBI PubMed PMID: 3430493, 1987 Nov.

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There were significant differences between DES-exposed women and their sisters in major depression and major recurrent depression. Papanicolaou controls were more depressed in comparison to sister controls.

However, there were no significant differences in depression between Papanicolaou controls and the DES exposed, suggesting that major and recurrent depressions are more likely to result from concern about reproductive and other gynecologic problems than from the hormonal effects of intrauterine exposure to DES.

Differences in amphetamine abuse/dependence were also noted between the DES exposed and the sister controls.

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Psychopathology in prenatally DES-exposed females

Current and lifetime adjustment

1987 Study Abstract

This report concerns the long-term effects of prenatal exposure to diethylstilbestrol (DES) on overall psychologic functioning in females.

Thirty DES-exposed women aged 17-30 years and 30 control women with a history of abnormal Pap smear findings were interviewed with the SADS-L and completed the SCL-90-R and the PRI-Q.

Psychopathology in prenatally DES-exposed females: current and lifetime adjustment, US National Library of Medicine, Psychosomatic medicine, NCBI PubMed PMID: 3575605, 1987 Mar-Apr.

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Both DES and PAP women showed elevated symptoms on the SCL-90-R in comparison to published norms and were similar to women with cancer, but their rates of psychiatric disorders (SADS-L/RDC) at the time of the evaluation did not differ from community norms. However, both groups met criteria for Major Depressive Disorder (lifetime) significantly above expectancy, and the DES women reported slightly more episodes than the control group. The DES women also had significantly more problems than the PAP control group in social relations with spouses and other significant persons.

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