Female fertility prognosis and diethylstilbestrol – high-risk pregnancies and successful childbearing

Adapted psychological and medical care can lead to successful childbearing

Las-manos-del-destino
In spite of their difficult past reproductive history 4 young DES-women conceived successfully with adapted psychological and medical care in 1998 in France. Las manos del destino.

1998 Study Abstract

Diethylstilbestrol (DES) exposure in utero in females is a cause of clear-cell adenocarcinoma of the cervix and of several anatomical and functional disorders of the genital tract. DES exposure must be evoked whenever counselling women for reproductive disorders.

In France around 80,000 women have had in utero DES exposure. The cases of 4 young women who consulted our Reproduction Center for reproductive disorders illustrate the usual difficulties faced by these patients.

In spite of their difficult past reproductive history (uterine malformations, repeated miscarriages, ectopic pregnancies) and low fertility rate, all four women conceived successfully, either after spontaneous or induced ovulation. We stress the need for adapted psychological and medical care which can lead to successful childbearing in the vast majority of these high-risk patients.

Sources and more information
  • Female fertility prognosis and diethylstilbestrol. Personal data and review of the literature, Journal de gynécologie, obstétrique et biologie de la reproduction, NCBI PMID: 9648005, 1998 Apr.
More DES DiEthylStilbestrol Resources

Les médicamenteurs – Documentaire sur l’industrie pharmaceutique

Un film ravageur, une enquête implacable

Documentaire 2008 de Stéphane Horel, Annick Redolfi et Brigitte Rossigneux.

Plus d’information
  • Le médicament : enfin un domaine où personne ne détrônera la France. Les Français sont-ils vraiment plus malades que le reste de l’humanité ? Ou bien y a-t-il d’autres explications à cette boulimie ? En mêlant interviews de fond et séquences d’animation en pâte à modeler, ce documentaire embarque les téléspectateurs dans le parcours du médicament au sein du système de santé français. Matérialisée par le décor d’une ville médicament, Pharmacity, cette promenade guidée ne néglige aucune étape. Des essais cliniques à la mise sur le marché, de l’évaluation thérapeutique à la fixation du prix, du matraquage marketing aux effets secondaires subis – en bout de chaîne – par les patients, les pouvoirs publics et l’industrie pharmaceutique y sont questionnés sans détours sur leurs responsabilités.
  • Regardez cette liste de vidéos sur l’industrie pharmaceutique sur notre chaîne YouTube.

Early-life exposure to DES induces life reprogramming of the mouse uterine epigenome

Neonatal exposure to DES induced permanent alterations in DNA methylation status of specific genes in mouse uteri

lab-mouse
Neonatal exposure to DES induced permanent alterations in DNA methylation status of specific genes in mouse uteri.

2008 Study Summary

We have provided evidence that early-life exposure of the mice to the xenoestrogen Diethylstilbestrol (DES) or the phytoestrogen GEN induces life reprogramming of the mouse uterine epigenome. Specific genes with no previously documented associations with the uterus were identified by an unbiased methylation profiling methodology. These genes encode proteins involved in a wide-range of cellular functions. Detailed studies were conducted on one of the reprogrammable genes, Nucleosomal Binding Protein 1 (Nsbp1), which is a nucleosome binding and transcriptional activation element. Our data support the paradigm that manifestation of early-life epigenetic reprogrammed gene expression in the mouse uterus is dependent on adult ovarian steroids and changes over the course of natural aging of the animal. The complex interplay among the type of estrogen, timing of exposure, reproductive status, and aging time line all significantly contribute to the phenotypical outcome of the epigenetic reprogramming in this model system.

Sources and Full Study
  • Persistent Hypomethylation in the Promoter of Nucleosomal Binding Protein 1 (Nsbp1) Correlates with Overexpression of Nsbp1 in Mouse Uteri Neonatally Exposed to Diethylstilbestrol or Genistein, NCBI, Endocrinology. 2008;149(12):5922-5931. doi:10.1210/en.2008-0682, PMC2613067, Dec 2008.
More DES DiEthylStilbestrol Resources

The association between in utero cigarette smoke exposure and age at menopause

Prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause

cigarette-and-pregancy image
In this cohort of participants predominantly exposed to diethylstilbestrol, results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause.

2008 Study Abstract

Menopause onset, on average, occurs earlier among women who smoke cigarettes than among women who do not smoke. Prenatal smoke exposure may also influence age at menopause through possible effects on follicle production in utero.

Smoking information was obtained from the mothers of 4,025 participants in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project, a US study begun in 1975 to examine the health effects of prenatal diethylstilbestrol exposure. Between 1994 and 2001, participants provided information on menopausal status. Cox proportional hazards modeling compared the probability of menopause among participants who were and were not prenatally exposed to maternal cigarette smoke.

Participants prenatally exposed to maternal cigarette smoke were more likely than those unexposed to be postmenopause (hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). The association was present among only those participants who themselves had never smoked cigarettes (hazard ratio = 1.38, 95% confidence interval: 1.10, 1.74) and was absent among active smokers (hazard ratio = 1.03, 95% confidence interval: 0.81, 1.31).

In this cohort of participants predominantly exposed to Diethylstilbestrol (DES) , results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause. The possibility that active cigarette smoking modifies this effect is also suggested.

Sources
More DES DiEthylStilbestrol Resources

Pesticide Exposure and Depression among Farmers and Farm Residents

Pesticide poisoning and depression in farm residents

Farm image
The studies support a positive association between pesticide exposure and depression, including associations with several specific pesticides.

Pesticide Exposure and Depression among Male Private Pesticide Applicators in the Agricultural Health Study

Background:
Pesticide exposure may be positively associated with depression. Few previous studies have considered the episodic nature of depression or examined individual pesticides.

Objective:
We evaluated associations between pesticide exposure and depression among male private pesticide applicators in the Agricultural Health Study.

Methods:
We analyzed data for 10 pesticide classes and 50 specific pesticides used by 21,208 applicators enrolled in 1993–1997 who completed a follow-up telephone interview in 2005–2010. We divided applicators who reported a physician diagnosis of depression (n = 1,702; 8%) into those who reported a previous diagnosis of depression at enrollment but not follow-up (n = 474; 28%), at both enrollment and follow-up (n = 540; 32%), and at follow-up but not enrollment (n = 688; 40%) and used polytomous logistic regression to estimate odds ratios (ORs) and 95% CIs. We used inverse probability weighting to adjust for potential confounders and to account for the exclusion of 3,315 applicators with missing covariate data and 24,619 who did not complete the follow-up interview.

Results:
After weighting for potential confounders, missing covariate data, and dropout, ever-use of two pesticide classes, fumigants and organochlorine insecticides, and seven individual pesticides—the fumigants aluminum phosphide and ethylene dibromide; the phenoxy herbicide (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T); the organochlorine insecticide dieldrin; and the organophosphate insecticides diazinon, malathion, and parathion—were all positively associated with depression in each case group, with ORs between 1.1 and 1.9.

Conclusions:
Our study supports a positive association between pesticide exposure and depression, including associations with several specific pesticides.

Depression and pesticide exposures among private pesticide applicators enrolled in the Agricultural Health Study

Background:
We evaluated the relationship between diagnosed depression and pesticide exposure using information from private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997 in Iowa and North Carolina.

Methods:
There were 534 cases who self-reported a physician-diagnosed depression and 17,051 controls who reported never having been diagnosed with depression and did not feel depressed more than once a week in the past year. Lifetime pesticide exposure was categorized in three mutually exclusive groups: low (< 226 days, the reference group), intermediate (226-752 days), and high (> 752 days). Two additional measures represented acute high-intensity pesticide exposures: an unusually high pesticide exposure event (HPEE) and physician-diagnosed pesticide poisoning. Logistic regression analyses were performed relating pesticide exposure to depression.

Results:
After adjusting for state, age, education, marital status, doctor visits, alcohol use, smoking, solvent exposure, not currently having crops or animals, and ever working a job off the farm, pesticide poisoning was more strongly associated with depression [odds ratio (OR) = 2.57; 95% confidence interval (CI), 1.74-3.79] than intermediate (OR = 1.07; 95% CI, 0.87-1.31) or high (OR = 1.11; 95% CI, 0.87-1.42) cumulative exposure or an HPEE (OR = 1.65; 95% CI, 1.33-2.05). In analysis of a subgroup without a history of acute poisoning, high cumulative exposure was significantly associated with depression (OR = 1.54; 95% CI, 1.16-2.04).

Conclusions:
These findings suggest that both acute high-intensity and cumulative pesticide exposure may contribute to depression in pesticide applicators. Our study is unique in reporting that depression is also associated with chronic pesticide exposure in the absence of a physician-diagnosed poisoning.

A cohort study of pesticide poisoning and depression in Colorado farm residents

Purpose:
Depressive symptoms have been associated with pesticide poisoning among farmers in cross-sectional studies, but no longitudinal studies have assessed the long-term influence of poisoning on depressive symptoms. The purpose of this study was to describe the associations between pesticide poisoning and depressive symptoms in a cohort of farm residents.

Methods:
Farm operators and their spouses were recruited in 1993 from farm truck registrations using stratified probability sampling. The Center for Epidemiologic Studies-Depression scale was used to evaluate depression in participants using generalized estimating equations. Baseline self-reported pesticide poisoning was the exposure of interest in longitudinal analyses.

Results:
Pesticide poisoning was significantly associated with depression in three years of follow-up after adjusting for age, gender, and marital status (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.20-5.58). Depression remained elevated after adjusting for health, decreased income, and increased debt (OR 2.00; CI 0.91-4.39) and was primarily due to significant associations with the symptoms being bothered by things (OR 3.29; CI 1.95-5.55) and feeling everything was an effort (OR 1.93; CI 1.14-3.27).

Conclusions:
Feeling bothered and that everything was an effort were persistently associated with a history of pesticide poisoning, supportive of the hypothesis that prolonged irritability may result from pesticide poisoning.

Sources and more information
  • Pesticide Exposure and Depression among Male Private Pesticide Applicators in the Agricultural Health Study, ehp, 1 September 2014.
  • Depression and pesticide exposures among private pesticide applicators enrolled in the Agricultural Health Study, NCBI PMID: PubMed 19079725, 2008 Sept 9.
  • A cohort study of pesticide poisoning and depression in Colorado farm residents, NCBI PMID: PubMed 18693039, 2008 Aug 9.

Interdits d’enfants

En 1998, après avoir découvert l’infertilité de Sylvie, un couple décide de devenir parents grâce à une mère porteuse, pratique illégale en France

Le témoignage unique de parents ayant eu recours à une mère porteuse

Résumé
image de couverture du livre interdits d'enfants
Le témoignage unique de parents ayant eu recours à une mère porteuse

Un couple de Français, Sylvie et Dominique, apprennent qu’ils ne pourront pas avoir d’enfants et décident de partir en Californie pour entamer une procédure de gestation pour autrui (GPA), c’est-à-dire faire appel à une mère porteuse, pratique illégale en France. De retour en France avec leurs jumelles, ils sont assignés en justice pour leurs actes et se battent pour faire valoir leurs droits.

Description de l’ouvrage

Sylvie et Dominique Mennesson sont les symboles malgré eux des révolutions familiales contemporaines. En 1998, après avoir découvert l’infertilité de Sylvie, ce couple décide de devenir parents grâce à une mère porteuse. Cette ” grossesse par procuration ” étant illégale dans notre pays, ils choisissent de se rendre en Californie un État américain précurseur en matière de gestation pour autrui (GPA). Après trois ans d’attente et d’espoirs déçus, Mary, leur gestatrice, donne naissance a deux superbes jumelles, Isa et Léa. Sylvie et Dominique sont enfin parents. Mais, en France, cette filiation est contestée et leurs filles se retrouvent comme des sans papiers, enfants de personne. Le couple va devoir affronter sans relâche la justice française pour être reconnu comme le père et la mère de leurs propres filles. Leur combat, soutenu par des personnalités telles qu’Élisabeth Badinter, Geneviève Delaisi de Parseval ou le professeur François Olivennes, va ébranler bien des certitudes et relancer le débat sur la bioéthique. Interdits d’enfants, l’histoire bouleversante d’une famille trop extraordinaire pour notre société et une réflexion intime sur les nouvelles formes de parenté.

En savoir plus
  • Commentaires en ligne, Amazon
  • CLARA, Comité de soutien pour la Légalisation de la GPA (Gestation Pour Autrui) et l’Aide à la Reproduction Assistée, créé par Sylvie et Dominique Mennesson
  • Gestation pour autrui, un véritable débat doit être mené en France, LeMonde, 07.02.2013
  • Un enfant, la vie : un vrai sujet pour la présidentielle 2012, HuffingtonPost, 10.02.2011
  • Mère porteuse: les Mennesson de retour au tribunal, ParisMatch, 06.04.2011 et Mère porteuse : le combat des Mennesson n’est pas terminé, ParisMatch, 23.03.2010

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Prescription Drugs Cost and Big Pharma: how the Lobbies rule America

The astronomically high health care costs in the United States explained…

You really think that you have a say in how your government functions, think again. This report describes a shocking revolving door system that works beyond our control.
The amount of money spent on lobbying and political contributions by the pharmaceutical industry has continued to increase since.
It is why you can’t pay your medical bills.
And it is happening behind the scenes so you never see it.
This report is a rare glimpse into how we lost our democracy.

More info and Videos

ASD: 1 in 88 Children aged 8 Years identified with an Autism Spectrum Disorder in the United States

Prevalence of Autism in the US, CDC, 2012

Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators

Abstract

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Problem/Condition:
Autism spectrum disorders (ASDs) are a group of developmental disabilities characterized by impairments in social interaction and communication and by restricted, repetitive, and stereotyped patterns of behavior. Symptoms typically are apparent before age 3 years. The complex nature of these disorders, coupled with a lack of biologic markers for diagnosis and changes in clinical definitions over time, creates challenges in monitoring the prevalence of ASDs. Accurate reporting of data is essential to understand the prevalence of ASDs in the population and can help direct research.

Period Covered:
2008.

Description of System:
The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that estimates the prevalence of ASDs and describes other characteristics among children aged 8 years whose parents or guardians reside within 14 ADDM sites in the United States. ADDM does not rely on professional or family reporting of an existing ASD diagnosis or classification to ascertain case status. Instead, information is obtained from children’s evaluation records to determine the presence of ASD symptoms at any time from birth through the end of the year when the child reaches age 8 years. ADDM focuses on children aged 8 years because a baseline study conducted by CDC demonstrated that this is the age of identified peak prevalence. A child is included as meeting the surveillance case definition for an ASD if he or she displays behaviors (as described on a comprehensive evaluation completed by a qualified professional) consistent with the American Psychiatric Association’s Diagnostic and Statistical Manual-IV, Text Revision (DSM-IV-TR) diagnostic criteria for any of the following conditions: Autistic Disorder; Pervasive Developmental Disorder–Not Otherwise Specified (PDD-NOS, including Atypical Autism); or Asperger Disorder. The first phase of the ADDM methodology involves screening and abstraction of comprehensive evaluations completed by professional providers at multiple data sources in the community. Multiple data sources are included, ranging from general pediatric health clinics to specialized programs for children with developmental disabilities. In addition, many ADDM sites also review and abstract records of children receiving special education services in public schools. In the second phase of the study, all abstracted evaluations are reviewed by trained clinicians to determine ASD case status. Because the case definition and surveillance methods have remained consistent across all ADDM surveillance years to date, comparisons to results for earlier surveillance years can be made. This report provides updated ASD prevalence estimates from the 2008 surveillance year, representing 14 ADDM areas in the United States. In addition to prevalence estimates, characteristics of the population of children with ASDs are described, as well as detailed comparisons of the 2008 surveillance year findings with those for the 2002 and 2006 surveillance years.

Results:
For 2008, the overall estimated prevalence of ASDs among the 14 ADDM sites was 11.3 per 1,000 (one in 88) children aged 8 years who were living in these communities during 2008. Overall ASD prevalence estimates varied widely across all sites (range: 4.8–21.2 per 1,000 children aged 8 years). ASD prevalence estimates also varied widely by sex and by racial/ethnic group. Approximately one in 54 boys and one in 252 girls living in the ADDM Network communities were identified as having ASDs. Comparison of 2008 findings with those for earlier surveillance years indicated an increase in estimated ASD prevalence of 23% when the 2008 data were compared with the data for 2006 (from 9.0 per 1,000 children aged 8 years in 2006 to 11.0 in 2008 for the 11 sites that provided data for both surveillance years) and an estimated increase of 78% when the 2008 data were compared with the data for 2002 (from 6.4 per 1,000 children aged 8 years in 2002 to 11.4 in 2008 for the 13 sites that provided data for both surveillance years). Because the ADDM Network sites do not make up a nationally representative sample, these combined prevalence estimates should not be generalized to the United States as a whole.

Interpretation:
These data confirm that the estimated prevalence of ASDs identified in the ADDM network surveillance populations continues to increase. The extent to which these increases reflect better case ascertainment as a result of increases in awareness and access to services or true increases in prevalence of ASD symptoms is not known. ASDs continue to be an important public health concern in the United States, underscoring the need for continued resources to identify potential risk factors and to provide essential supports for persons with ASDs and their families.

Public Health Action:
Given substantial increases in ASD prevalence estimates over a relatively short period, overall and within various subgroups of the population, continued monitoring is needed to quantify and understand these patterns. With 5 biennial surveillance years completed in the past decade, the ADDM Network continues to monitor prevalence and characteristics of ASDs and other developmental disabilities for the 2010 surveillance year. Further work is needed to evaluate multiple factors contributing to increases in estimated ASD prevalence over time. ADDM Network investigators continue to explore these factors, with a focus on understanding disparities in the identification of ASDs among certain subgroups and on how these disparities have contributed to changes in the estimated prevalence of ASDs. CDC is partnering with other federal and private partners in a coordinated response to identify risk factors for ASDs and to meet the needs of persons with ASDs and their families.

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Significant Alterations in Uterine Gene Expression following NeoNatal DiEthylStilbestrol Treatment

Developmental exposure to DES alters uterine gene expression that may be associated with uterine neoplasia later in life

Abstract:

PubMed logo
Significant Alterations in Uterine Gene Expression following NeoNatal DiEthylStilbestrol Treatment

Previously, we described a mouse model where the well-known reproductive carcinogen with estrogenic activity, diethylstilbestrol (DES), caused uterine adenocarcinoma following neonatal treatment. Tumor incidence was dose-dependent reaching >90% by 18 mo following neonatal treatment with 1000 μg/kg/d of DES. These tumors followed the initiation/promotion model of hormonal carcinogenesis with developmental exposure as initiator, and exposure to ovarian hormones at puberty as the promoter. To identify molecular pathways involved in DES-initiation events, uterine gene expression profiles were examined in prepubertal mice exposed to DES (1, 10, or 1000 μg/kg/d) on days 1–5 and compared to controls. Of more than 20 000 transcripts, approximately 3% were differentially expressed in at least one DES treatment group compared to controls; some transcripts demonstrated dose–responsiveness. Assessment of gene ontology annotation revealed alterations in genes associated with cell growth, differentiation, and adhesion. When expression profiles were compared to published studies of uteri from 5-d-old DES-treated mice, or adult mice treated with 17β estradiol, similarities were seen suggesting persistent differential expression of estrogen responsive genes following developmental diethylstilbestrol exposure. Moreover, several altered genes were identified in human uterine adenocarcinomas. Four altered genes [lactotransferrin (Ltf), transforming growth factor beta inducible (Tgfb1), cyclin D1 (Ccnd1), and secreted frizzled-related protein 4 (Sfrp4)], selected for real-time RT-PCR analysis, correlated well with the directionality of the microarray data. These data suggested altered gene expression profiles observed 2 wk after treatment ceased, were established at the time of developmental exposure and maybe related to the initiation events resulting in carcinogenesis.

Sources:

NCBIDr Retha Newbold, PMCID: PMC2254327 25 Feb 2008 – Developmental exposure to diethylstilbestrol alters uterine gene expression that may be associated with uterine neoplasia later in life.

More DES DiEthylStilbestrol Resources

Offspring of Women exposed in Utero to DiEthylStilbestrol: malignant pathology in Third Generation

Increased risk of ovarian cancer in DES Grand Daughters

DES Follow-up Study Summary

National Cancer Inst logo image
Increased risk of ovarian cancer in DES Grand Daughters.

Studies have shown a slightly increased risk of breast cancer in women who were given Diethylstilbestrol (DES) while they were pregnant. Their daughters, who were exposed to DES prenatally (before they were born), have an elevated risk of reproductive tract conditions, including a rare vaginal cancer. A question now being studied is whether DES health effects can be passed from the prenatally exposed women to their offspring (intergenerational transmission).

Studies in mice suggest that intergenerational transmission of DES health effects may be possible. Recent evidence indicates that prenatal exposure to DES may cause changes in the behavior of genes that influence hormones and the development of the female reproductive tract. These changes in gene behavior may be passed on to the next generation. Evidence for intergenerational transmission comes from mouse studies showing a higher number of reproductive tract tumors in the daughters of prenatally exposed female mice. We used the DES Follow-up Study data to assess whether cancer was more common in the offspring of women who were prenatally exposed to DES. Cancers affecting these offspring (the third generation) were identified using two approaches. First, we asked women participating in the DES Follow-up Study to report cancers diagnosed in their 8,216 third generation sons and daughters. Second, we asked 793 third generation daughters participating in the Third Generation Study to tell us about their cancers. We also asked the third generation daughters to tell us about their reproductive tract and breast biopsies. Next we confirmed the reported biopsies and cancers by checking the medical records of these third generation daughters.

Our results did not show an overall increase of cancer in the sons or in the daughters of prenatally DES-exposed women. However, based on only three cases, the number of ovarian cancers was higher than expected in the daughters of women exposed prenatally to DES. Because of the small number of cases, this result must be considered preliminary. The association may be a chance finding or may be due to the way in which the data were reported or collected. We did not find an association between DES and benign breast disease or reproductive tract conditions, but most of the women are too young for a meaningful assessment of these outcomes. Further follow-up is needed to assess whether prenatal DES exposure can affect the third generation in humans.

2008 Study Abstract

BACKGROUND:
Animal studies suggest that prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes epigenetic changes that may be transmitted to the next generation. Specifically, these studies show an elevated incidence of reproductive tumors in the female offspring of prenatally-exposed mice.

METHODS:
We assessed cancer and benign pathology diagnoses occurring in the offspring of women whose prenatal exposure to DES (or lack of exposure) was verified by medical record. Our data arose from 2 sources: the mothers’ reports of cancers occurring in 8216 sons and daughters, and pathology-confirmed cancers and benign diagnoses self-reported by a subset of 793 daughters.

RESULTS:
Although statistical power is limited, our data are consistent with no overall increase of cancer in the sons or daughters of women exposed in utero to DES. Based on pathology-confirmed diagnoses reported by the daughters, we saw no association between DES and risk of benign breast disease or reproductive tract conditions. Based on 3 cases, the incidence of ovarian cancer was higher than expected in the daughters of women exposed prenatally to DES.

CONCLUSIONS:
Our data do not support an overall increase of cancer risk in the sons or daughters of women exposed prenatally to DES, but the number of ovarian cancer cases was greater than expected. While preliminary, this finding supports continued monitoring of these daughters.

Sources

  • Offspring of women exposed in utero to diethylstilbestrol (DES): a preliminary report of benign and malignant pathology in the third generation,NCBI, PMID: 18223485, 2008 Mar;19(2):251-7. doi: 10.1097/EDE.0b013e318163152a.
  • NCI, DES Follow-up Study Published Papers.
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