Gender-identity, body-experience, sexuality, and the wish for having children in women exposed prenatally to diethylstilbestrol

US National Library of Medicine National Institutes of Health, 1996

Study Abstract

The main focus of the present study is to examine the impact of being a DES-daughter upon gender-identity, body-experience, body-acceptance, sexual satisfaction, and the wish for having children.

Gender-identity, body-experience, sexuality, and the wish for having children in DES-daughters, Women’s Health, NCBI PubMed PMID: 8948086, 1996.

Pink & Blue image credit Janet McKnight.

Subjects were DES-daughters (N = 206) and age-matched controls (N = 121) who were not prenatally exposed to DES.

All subjects completed a battery of measures including Bem’s Sex Role Inventory (1977), a written gynecological anamnesis, and questionnaires concerning body-experience, sexuality, and the wish for having children.

  1. First, it was expected that DES-daughters would be more masculinized in their self-concepts than non-exposed control subjects.
  2. Our second hypothesis was that DES-daughters would be lower in body-acceptance and sexual satisfaction, and would have stronger wishes and more emotionality concerning reproduction.

Contrary to expectations, DES-daughters were not more ‘masculinized’ than controls. Instead, they tended to have higher scores on femininity.

Furthermore, no differences between DES-daughters and controls appeared in body-acceptance and sexual satisfaction. However, the DES-daughters reported a stronger wish for having children and expressed more emotionality concerning the subject.

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Gender-related behavior in women prenatally exposed to DES

Diethylstilbestrol exposures influence brain development and the differentiation of the central nervous system

1993 Study Abstract

Accumulating evidence in experimental animals over the past three decades suggests that mammalian brain development and differentiation of the central nervous system are influenced by perinatal exposure to sex hormones.

Gender-related behavior in women exposed prenatally to diethylstilbestrol, US National Library of Medicine National Institutes of Health, Environmental health perspectives, NCBI PubMed PMID: 8404755, 1993 Aug.

Dancing statues image credit Oiluj Samall Zeid.

Hence, changes in human behavioral patterns may be associated with prenatal exposure to estrogenic substances such as diethylstilbestrol (DES).

This paper reviews relevant studies from a series of laboratories and finds that no clear-cut differences can be demonstrated to date between unexposed and DES-exposed women in gender-related behavior, although the physical and psychological impact of the problems associated with exposure to DES are well documented.

If both prenatal and postnatal influences such as social, economic, and environmental factors are taken into consideration, individual variation is more apparent than differences in gender-related behavior between unexposed and DES-exposed women.

In summary, gender-related behavior is determined by a complex array of interacting factors, and prenatal influences are only one of many developmental events. More studies are needed using larger populations with carefully controlled selection criteria to suggest a direct role of prenatal DES exposure on subsequent gender-related behavior.

Download (free access) the full PDF on NCBI.

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Female gene expression in the seminal vesicle after prenatal exposure to DES

Feminization of the male mouse reproductive tract after prenatal exposure to Diethylstilbestrol

1989 Study Abstract

Previous studies from our laboratory on the feminization of the male mouse reproductive tract after prenatal exposure to diethylstilbestrol (DES) showed that the mRNA for the major estrogen-inducible uterine secretory protein, lactoferrin (LF), was constitutively expressed in the seminal vesicle of male mice exposed prenatally to DES, but not in the seminal vesicle of control mice.

Female gene expression in the seminal vesicle of mice after prenatal exposure to diethylstilbestrol, US National Library of Medicine National Institutes of Health, Endocrinology, NCBI PubMed PMID: 2707167, 1989 May.

Lactoferrin image credit wikipedia.

After castration, treatment with 17 beta-estradiol (20 micrograms/kg.day) for 3 days induced the LF mRNA in the seminal vesicle of both control and prenatally DES-exposed mice; however, the levels in DES-treated tissues were approximately 6-fold higher than those in control tissue.

This report describes the presence of LF in seminal vesicle tissues and secretions of prenatally DES-exposed mice, as determined by immunohistochemistry and Western blot analysis.

Further, these data are correlated with immunolocalization of the estrogen receptor in the seminal vesicle tissue.

We conclude that the seminal vesicle of prenatally DES-exposed male mice has acquired two key characteristics of female tissues, namely LF production/regulation and estrogen receptor localization/distribution similar to that in uterine tissues.

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Prenatal exposure to DES alter the expression of the lactotransferrin gene in seminal vesicles

Feminization of the male mouse reproductive tract after prenatal exposure to DES

1988 Study Abstract

We have previously isolated an estrogen-inducible secretory protein, lactotransferrin (LTF), and a cDNA to its messenger RNA from the uterus of mice.

Prenatal exposure of male mice to diethylstilbestrol alter the expression of the lactotransferrin gene in seminal vesicles, US National Library of Medicine National Institutes of Health, Molecular endocrinology (Baltimore, Md.), NCBI PubMed PMID: 3216864, 1988 Dec.

Image credit research gate.

In this report we determined that the level of LTF mRNA is minimal in the seminal vesicles of normal mice.

In contrast, expression of LTF mRNA in the seminal vesicles of developmentally estrogenized males was both constitutive and estrogen inducible.

The mRNA for the major estrogen-inducible uterine secretory protein, lactoferrin (LF), was constitutively expressed in the seminal vesicle of male mice exposed prenatally to DES, but not in the seminal vesicle of control mice. The results suggested that this alteration may be an example of atypical gene expression after hormonal manipulation early in development.

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Endocrine disruptors and psychiatric disorders in children exposed in utero

Evidence from a French cohort of 1002 prenatally exposed children and the example of diethylstilbestrol (DES) as a model for PE study

2016 Study Abstract

Aim of the work In utero diethylstilbestrol (DES) exposure has been demonstrated to be associated with somatic abnormalities in adult men and women as well as shown for its trangenerationnal effect.

Endocrine disruptors and psychiatric disorders in children exposed in utero: evidence from a French cohort of 1002 prenatally exposed children and the example of diethylstilbestrol (DES) as a model for PE study, Conference Paper, Research Gate, publication/293333931, January 2016.

Researchers Marie-Odile Soyer-Gobillard and Charles Sultan, image credit lamarseillaise.

Conversely, the data are contradictory regarding the association with psychological or psychiatric disorders during adolescence and adulthood.

This work was designed to determine whether prenatal exposure to DES and/or Ethinyloestradiol affects brain development and whether it is associated with psychiatric disorders in male and female adolescents and young adults.

Methods
HHORAGES Association, a national patient support group, has assembled a cohort of 1280 women (spontaneous testimonies communicated after various informations) who took DES and/or EE during pregnancy. We obtained responses to detailed questionnaire from 529 families, corresponding to 1182 children divided into three groups:

  1. Group 1 (n=180): firstborn children without DES treatment,
  2. Group 2 (n=740): exposed children,
  3. and Group 3 (n=262): children born after a previous pregnancy treated by DES and/or EE.

Key Results
No psychiatric disorders were reported in Group 1. In Group 2, the incidence of psychiatric disorders was drastically elevated (83.8%), and in Group 3, the incidence was still elevated (6.1%) compared with the general population.

Total number of psychological/psychiatric disorders among the 982 (1002-20 stillborns) DES-exposed and post-DES children
Among the 982 DES-exposed adolescents (1002-20 stillborns) (Group 2) and post-DES adolescents (Group 3):

  • Behavioral disorders, violence, aggressiveness, obsessive-compulsive disorders (n=110) (11.2%)
  • Eating disorders (n=83) (8.4%)
  • Schizophrenia (n=171) (17.4%)
  • Depression, bipolar disorders, anxiety (n=257) (26.2%)
  • Suicides (n=33) (3.4%)
  • Suicide attempts (n=642) (65.4%)

Conclusions
This work demonstrates that prenatal exposure to DES and/or EE is associated with a high risk of psychiatric disorders in adolescence and adulthood. Molecular epigenetic mechanisms subtending these toxic effects are in progress.

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Prenatal exposure to endocrine disruptors and neurodevelopment risk

Study of siblings exposed to diethylstilbestrol

2015 Study Abstract

Many endocrine disruptors are found in our environment. They act on hormonal receptors, on their action and synthesis. They may alter neuronal transmission and neuronal formation.

Exposition prénatale aux perturbateurs endocriniens et risque sur le neurodéveloppement : étude de fratries exposées au diéthylstilbestrol, UPD5 Médecine – Université Paris Descartes – Faculté de Médecine, dumas-01213114, October 7, 2015.

Image credit open archive HAL.

A lot of neurodevelopmental diseases have a growing prevalence, raising many questions about a possible association with endocrine disruptors. One of their action mechanisms may be an effect on DNA methylation of the developing brain.

Objectives
To study neurodevelopmental characteristics and the epigenetic signature of patients exposed in utero to diethylstilbestrol. To identify differentially methylated regions in neurodevelopmental related genes, which could lead to a psychiatric vulnerability.

Materials and Methods
We recruited 75 siblings from 31 families, in which at least one member was exposed in utero to diethylstilbestrol. A psychiatric evaluation was assessed with standardized questionnaires. We used the Infinium HumanMethylation450 BeadChip and analyzed the methylation variations of 411 947 CpG loci.

Results
We found clinical differences in non-specific psychiatric symptoms and in neurological soft signs, such as lateralization, associated with the exposure. We found several biological pathways in which methylation modifications were associated to diethylstilbestrol exposure. These pathways are implicated in neurodevelopmental pathways, general metabolism and oncogenesis mostly.

Conclusion
Prenatal diethylstilbestrol exposure seems associated with non-specific psychiatric symptoms, lateralization abnormalities and methylation alterations in genes that participate to pathways known to be involved in psychiatric diseases, notably in neurotransmitters signalization.

Note
The 100 pages complete study – THÈSE POUR LE DIPLÔME D’ÉTAT DE DOCTEUR EN MÉDECINE – is available (free access) in French language on HAL archives-ouvertes.

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Impact of prenatal exposure to DES on psychological outcome

A national survey of DES daughters and unexposed controls

2017 STUDY ABSTRACT

Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome: a national survey of DES daughters and unexposed controls, US National Library of Medicine National Institutes of Health, Archives of women’s mental health, NCBI PubMed PMID: 28064340, 2017 Jan 7.

Image credit Maciej Kraus.

To explore whether prenatal exposure to diethylstilbestrol (DES) is associated with increased risk of poor psychological outcome independently of the occurrence of major somatic complications related to DES exposure. Data on health outcome were collected in women prenatally exposed to DES (n = 2566) and unexposed women (n = 2967) recruited in a French national survey.

Women prenatally exposed to DES were 1.7 times more likely to have consulted a mental health specialist compared to unexposed women (adjusted odds ratio = 1.69, 95% confidence interval 1.47-1.96), independently of demographic characteristics, poor gynecological or obstetrical outcome, or history of cancer.

Frequency of consultation with a mental health specialist in persons with a history of gynecological complications or cancer was comparable in women prenatally exposed to DES and unexposed women.

Findings regarding psychological outcome obtained in the high-risk group of women prenatally exposed to DES may contribute to improving identification of psychological needs of all women presenting with gynecological abnormalities.

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Association between fetal DES-exposure and psychiatric disorders in adolescence/adulthood

Evidence from a French cohort of 1002 prenatally exposed children

2016 STUDY ABSTRACT

Association between fetal DES-exposure and psychiatric disorders in adolescence/adulthood: evidence from a French cohort of 1002 prenatally exposed children, US National Library of Medicine National Institutes of Health, The official journal of the International Society of Gynecological Endocrinology, NCBI PubMed PMID: 26172930, 2016 Sep.

Image credit JustCallMe_Bethy.

In utero diethylstibestrol (DES) exposure has been demonstrated to be associated with somatic abnormalities in adult men and women. Conversely, the data are contradictory regarding the association with psychological or psychiatric disorders during adolescence and adulthood. This work was designed to determine whether prenatal exposure to DES affects brain development and whether it is associated with psychiatric disorders in male and female adolescents and young adults.

HHORAGES Association, a national patient support group, has assembled a cohort of 1280 women who took DES during pregnancy. We obtained questionnaire responses from 529 families, corresponding to 1182 children divided into three groups:

  1. Group 1 (n=180): firstborn children without DES treatment,
  2. Group 2 (n=740): exposed children,
  3. and Group 3 (n=262): children born after a previous pregnancy treated by DES.

No psychiatric disorders were reported in Group 1.
In Group 2, the incidence of disorders was drastically elevated (83.8%),
and in Group 3, the incidence was still elevated (6.1%) compared with the general population.

This work demonstrates that prenatal exposure to DES is associated with a high risk of psychiatric disorders in adolescence and adulthood.

More DES DiEthylStilbestrol Resources

DES and the risk of psychiatric disorders

image of depression

A critical review and new insights

2012 Study Abstract

Diethylstilbestrol and risk of psychiatric disorders: a critical review and new insights, US National Library of Medicine National Institutes of Health, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, NCBI PubMed PMID: 21428730, 2012 Feb.

Image credit Karina Lamontagne.

OBJECTIVES
We explored whether in utero DES exposure has produced consistent findings with regard to an increased risk of psychiatric disorders.

METHODS
We reviewed systematically the epidemiological studies investigating a possible association between prenatal DES exposure and risk of psychiatric disorders.

RESULTS
We identified 10 relevant studies reporting the psychiatric outcome of offspring with a history of in utero DES exposure compared to a control group.

We classified them into four categories:

  1. a mail survey in a sample from a randomized double-blind controlled trial of prophylactic DES for first pregnancy in the early 1950s reported that depression and anxiety were twice as frequent in the exposed group compared to the placebo group;
  2. five small clinical samples with inconclusive results;
  3. two large cohorts of DES-exposed participants:
    1. the first study reported a higher lifetime history of weight loss related to anorexia nervosa
    2. the second did not found any significant difference;
  4. two subsamples from general population cohorts:
    1. the first study did not found any significant difference
    2. the second reported that exposed women showed a higher rate of incident depression than non-exposed women.

CONCLUSIONS
The role of prenatal exposure to DES as an environmental risk factor for psychiatric disorders requires more evidence before any conclusions can be drawn. If confirmed, several explanations could be proposed: gene × environment interaction and epigenetic mechanisms, although phenocopy and gene-environment aggregation are plausible.

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Prenatal estrogens and the development of homosexual orientation

image of homosexual orientation

DES Daughters more likely to be rated as bisexual or homosexual

1995 Study Abstract

In psychobiological research on sexual orientation, the prenatal hormone theory has a central position.

Prenatal estrogens and the development of homosexual orientation, Developmental Psychology, ResearchGate, January 1995.

Image credit torbakhopper.

This article examines the hypothesis that prenatal estrogens contribute to the development of human sexual orientation.

Several groups of women with a history of prenatal exposure to diethylstilbestrol (DES), a nonsteroidal synthetic estrogen, were compared with several samples of control women in the context of a comprehensive study of the psychiatric and psychologic effects of prenatal DES.

Various aspects of sexual orientation were assessed by systematic interview.

Consistently across samples, more DES-exposed women than controls were rated as bisexual or homosexual (scores 2–6 on Kinsey-format scales ranging from 0 to 6).

The data are compatible with the hypothesis that prenatal estrogens may play a role in the development of human sexual orientation.

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