Over 50 years later, DES’ adverse effects continue

Women Exposed to DiEthylStilbestrol In Utero Face Ongoing Risks for Adverse Health Outcomes

October 8th, 2011, NEJM Journal Watch talked with two authors of the reportAdverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol“.

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Psychological consequences of DES exposure in utero

DES and Psychiatric Disorders, Prescrire international, 2011

image of psychological-disorder
This 2011 data suggest that persons exposed to DES in utero have an increased risk of experiencing psychological disorders and should be monitored accordingly. Splashes approximating big.

2011 Study Abstract

Between the 1950s and the late 1970s, millions of women worldwide took diethylstilbestrol (DES) during pregnancy. It was claimed that DES prevented miscarriage, even though a clinical trial was interrupted in 1953 when an interim analysis showed no beneficial effect in the prevention of miscarriage. In 1971, it emerged that DES exposure in utero was associated with somatic effects in adulthood, including female genital abnormalities with obstetric consequences, vaginal cancer, and male urogenital disorders.

This article examines the psychological effects of exposure to DES in utero, based on a review of the literature using the standard Prescrire methodology.

  • In two experimental studies, mice exposed to DES during gestation were found to be more aggressive than unexposed mice.
  • A randomised clinical trial and epidemiological studies have pointed to a risk of psychological disorders during adolescence and adulthood after DES exposure in utero.
  • A placebo-controlled randomised trial of DES was conducted in London in the 1950s but was never published.
  • In the 1980s, a research team recovered some of the original data and obtained information on the adult health status of the persons exposed in utero. Compared to the placebo group, psychological disorders were twice as frequent in the adults who were likely to have been exposed to DES in utero.
  • Three large epidemiological studies were also conducted.
    • One study showed that major depressive episodes were about 1.5 times more frequent in women exposed to DES in utero than in unexposed women;
    • the second showed that exposed women had an episode of major weight loss more often than unexposed women;
    • while the third showed no significant difference between the groups in terms of depressive episodes.
  • Smaller studies also suggest that depressive episodes tend to be more frequent after DES exposure in utero.

In practice, these data suggest that persons exposed to DES in utero have an increased risk of experiencing psychological disorders and should be monitored accordingly.

Sources and more information
  • Psychological consequences of DES exposure in utero, Prescrire international, NCBI PMID: 22066313, 2011 Nov.
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Prenatal exposure to progesterone suppresses reproduction in male mice

P. Sreenivasula Reddy, Harini Challa, Sainath S.B, Sep 2011

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.

Partial recovery of reproduction by testosterone

The role of androgens in development of male reproductive organs is well documented. The role of estrogens in the development of male reproductive organs remains largely unknown; although both estrogen receptors and aromatase enzyme have been identified in the developing penis of a number of species, including humans.

Male offspring of women exposed to diethylstilbestrol during pregnancy have higher incidences of epididymal cysts, cryptorchidism, hypospadiasis, and smaller testes.

Since female hormones were routinely prescribed to treat threatened pregnancy and considering the potential implications of female hormones during prenatal period on the development of male reproductive system, the present book describes the effect of prenatal exposure to progesterone on adult male reproduction.

Significant deterioration in reproduction was observed in mice exposed to progesterone during embryonic development which includes reduction in steroidogenesis and spermatogenesis. Testosterone supplementation during post-natal period partially restored the suppressed reproduction.

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Cryptorchidism and endocrine disrupting chemicals

DES exposure has been associated with increased risk of cryptorchidism

When evaluating associations between fetal exposure to estrogenic agents and cryptorchidism in humans, exposure to DES was associated with an increased risk of cryptorchidism. Image by Alon.

2011 Study Abstract

Prospective clinical studies have suggested that the rate of congenital cryptorchidism has increased since the 1950s. It has been hypothesized that this may be related to environmental factors. Testicular descent occurs in two phases controlled by Leydig cell-derived hormones insulin-like peptide 3 (INSL3) and testosterone. Disorders in fetal androgen production/action or suppression of Insl3 are mechanisms causing cryptorchidism in rodents. In humans, prenatal exposure to potent estrogen Diethylstilbestrol (DES) has been associated with increased risk of cryptorchidism. In addition, epidemiological studies have suggested that exposure to pesticides may also be associated with cryptorchidism. Some case–control studies analyzing environmental chemical levels in maternal breast milk samples have reported associations between cryptorchidism and chemical levels. Furthermore, it has been suggested that exposure levels of some chemicals may be associated with infant reproductive hormone levels.

  • Background
  • Testicular descent
  • Animal studies
  • Human studies
    1. Exposure to estrogens/estrogenic agents
    2. Pesticides
    3. PCBs
    4. Dioxins
    5. Flame retardants
    6. Phthalates

2011 Study Conclusion

Various xenobiotics have been found to disrupt the endocrine system in animals. Reduction in the dominance of androgens to estrogens, and interference with androgen or Insl3 production or action during fetal life, are apparent mechanisms causing cryptorchidism in animals. When evaluating associations between fetal exposure to estrogenic agents and cryptorchidism in humans, exposure to DES was associated with an increased risk of cryptorchidism. Studies evaluating pesticide use in a geographical area or parental possible occupational exposure to pesticides, have suggested that also exposure to them may be associated with an increased risk of cryptorchidism in boys. Some case–control studies evaluating maternal breast milk levels of chemicals have reported associations between congenital cryptorchidism and the levels of environmental chemicals with possible endocrine disrupting activities. No clear positive association was reported in studies evaluating levels of endocrine disrupting chemicals in placenta, cord serum or maternal serum. Maternal breast milk phthalate and PBDE levels have shown anti-androgen-like associations with infant reproductive hormone levels. More studies are needed to confirm the observed associations and to evaluate associations between cryptorchidism and combined exposures.

Sources and more information

  • Cryptorchidism and endocrine disrupting chemicals, sciencedirect pii/S0303720711006782, doi:10.1016/j.mce, 2011.11.
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Hormone Disruptors Linked To Genital Changes and Sexual Preference

Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses

Tyrone Hayes’ at work in his lab in Berkeley

Scientists are continuing to sound the alarm about some common chemicals, including the herbicide atrazine, and link them to changes in reproductive health and development. Endocrine disrupting toxic chemicals have been found to feminize male frogs and cause homosexual behavior. Ashley Ahearn reports on how these substances may be affecting human development and behavior.

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Our Bodies, Ourselves

2011 Edition by Boston Women’s Health Book Collective

our-bodies book cover image
Watch @DES_Journal diaporama and DES album on Flickr.

This highly respected publication provides women with information about health, sexuality and reproduction. This 2011 edition includes DES information provided by DES Action USA.

This newly revised and updated edition focuses on women’s reproductive health and sexuality. It includes dozens of personal stories and essential, up-to-date information about gender identity, sexual orientation, birth control, abortion, pregnancy and birth, perimenopause, menopause, health issues such as breast and ovarian cancers, and sexuality and sexual health as we age.

The book also features stories from OBOS’s Global Network partners who engage in public health outreach and advocacy, often at great risk, using materials they developed based on “Our Bodies, Ourselves.”

Hundreds of writers and reviewers collaborated to ensure the book’s accuracy and comprehensiveness, resulting in an essential text that provides evidence-based information and addresses the political, economic and social forces that shape women’s health.

Sources and book reviews

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Overdose Deaths from Prescription PainKillers have SkyRocketed during the Past Decade in the US

Use prescription painkillers only as directed by a health care provider
Get help for substance abuse problems if needed (1-800-662-HELP)

Prescription Painkiller Overdoses in the US 2011
Use prescription painkillers only as directed by a health care provider – Get help for substance abuse problems if needed (1-800-662-HELP) – @CDC_eHealth

Deaths from prescription painkillers – opioid or narcotic pain relievers, including drugs such as Vicodin (hydrocodone), OxyContin (oxycodone), Opana (oxymorphone), and methadone – have reached epidemic levels in the past decade. The number of overdose deaths is now greater than those of deaths from heroin and cocaine combined.

A big part of the problem is nonmedical use of prescription painkillers—using drugs without a prescription, or using drugs just for the “high” they cause. In 2010, about 12 million Americans (age 12 or older) reported nonmedical use of prescription painkillers in the past year.

Enough prescription painkillers were prescribed in 2010 to medicate every American adult around-the-clock for a month. Although most of these pills were prescribed for a medical purpose, many ended up in the hands of people who misused or abused them.

Improving the way prescription painkillers are prescribed can reduce the number of people who misuse, abuse or overdose from these powerful drugs, while making sure patients have access to safe, effective treatment.

  • Prescription Painkiller Overdoses in the US, CDC, painkilleroverdoses, November 2011 – PDF.
  • Vital Signs: Overdoses of Prescription Opioid Pain Relievers — United States, 1999–2008, CDC, mm6043a4.htm, November 4, 2011

Wormwood Herb – Artemisinin: a Cancer Smart Bomb

A Chinese herb that is safe, easy to use, affordable, and has great promise in cancer treatment

Wormwood is a Chinese herb that is thousands of years old that has applications for malaria and the treatment of cancer. It is safe, easy to use, affordable, and has great promise in the treatment of cancer. Video by DoctorSaputo, published on 26 Jul 2011.

More info and Videos

  • There are three forms of wormwood extract: artemisinin, artsunate, and artemether. It can be given either orally or by rectal suppository and should be pulsed with several days on and several off if taken by mouth because of intestinal tolerance. It is non-toxic and has been used on over 4000 patients without problems.
  • Artemisinin: A Cancer Smart Bomb, doctorsaputo, 04/26/2014.
  • More videos and our DES Videos in English playlist on YouTube.

Le Distilbène et les médecins prescripteurs

Vidéo d’archives C Dans L’Air 2011,
Intervention de Marc Girard, spécialiste en pharmacovigilance

Les Français plus grands consommateurs d’antibiotiques!
Médecins prescripteurs du Distilbène DES responsables?

  • Vidéo par edgarddevaux, 11 Jul 2011.
  • C Dans L’Air. Médicaments: le grand inventaire.
    Intervention de Marc Girard, spécialiste en pharmacovigilance.
Le Distilbène DES, en savoir plus

La face cachée des médicaments

La dérive du système de santé français

La face cachée des médicaments, par @nicole_delepine sur Flickr
La dérive du système de santé français, orienté par les lobbies pharmaceutiques.

Les scandales successifs du Distilbène, du Vioxx ou du Mediator, retirés très tardivement du marché, ne sont pas arrivés par hasard. La «chaîne du médicament» de la recherche pré- clinique aux essais thérapeutiques en passant par l’autorisation de mise sur le marché (AMM), la fixation des prix, le taux de remboursement et la surveillance post-AMM souffre d’innombrables dysfonctionnements.
Désormais les firmes pharmaceutiques contrôlent presque tout, et la pression populaire, instrumentalisée par la propagande publicitaire, a conduit à une accélération du processus de commercialisation. Le médicament est devenu une marchandise qui obéit essentiellement à l’économie de marché.

Nicole Delépine dresse ici un tableau sans complaisance de la dérive du système de santé français, orienté par les lobbies pharmaceutiques. Elle tente de sensibiliser les patients aux dangers des médicaments et d’alarmer médias et politiques sur leur passivité.
Une analyse argumentée et courageuse qui propose des solutions pour sortir de ce cercle infernal et imposer une véritable démocratie sanitaire.

Nicole Delépine est responsable de l’unité d’oncologie pédiatrique de l’hôpital universitaire Raymond Poincaré à Garches. Fille de l’un des fondateurs de la Sécurité Sociale et thérapeute engagée, elle a récemment publié La face cachée des médicaments et Le cancer, un fléau qui rapporte. Les commentaires en ligne et les articles par Nicole Delépine.

Sur Flickr®

Le Distilbène DES, en savoir plus