Diethylstilbestrol and risk of psychiatric disorders: a critical review and new insights

Association between fetal DES-exposure and psychiatric disorders ; another DES tragedy?

image of depression
The researchers identified ten relevant studies reporting the psychiatric outcome of offspring with a history of in utero DES exposure compared to a control group. Depression by Karina Lamontagne.

2012 Study Abstract

OBJECTIVES:
We explored whether in utero Diethylstilbestrol (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. whereas 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. whereas 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.

Sources and more information
More DES DiEthylStilbestrol Resources

Eggfreezing Techniques compared: vitrification Vs slow freezing

Is too much hope placed in egg freezing?

image of frozen-in-time
In the past five years, a new technique for freezing eggs called vitrification has been shown to be more effective than the older method, known as slow freezing. Vitrification involves a very rapid freezing process which is thought to cause less damage to the eggs and therefore increase the chances of achieving a pregnancy when the eggs are thawed. Frozen in time image by Ophelia photos.

2014 Study Abstract

BACKGROUND:
Oocyte cryopreservation is a technique with considerable potential in reproductive medicine, including fertility preservation, as a way of delaying childbearing and as part of oocyte donation programs. Although the technique was relatively ineffective at first more recently numerous modifications have led to higher success rates.

OBJECTIVES:
To compare the effectiveness and safety of vitrification and slow freezing as oocyte cryopreservation techniques for fertility outcomes in women undergoing assisted reproduction.

SEARCH METHODS:
We searched electronic databases, trial registers and websites, including the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO (date of search 3 March 2014).

SELECTION CRITERIA:
Two review authors independently selected randomised controlled trials (RCTs) comparing vitrification and slow freezing for oocyte preservation in women undergoing assisted reproduction.

DATA COLLECTION AND ANALYSIS:
Two review authors independently extracted the data from eligible studies and assessed their risk of bias. Any disagreements were resolved by discussion or by a third review author. Data extracted included study characteristics and outcome data. The overall quality of the evidence was assessed using GRADE methods.

MAIN RESULTS:
Two RCTs were included in the review (106 participants). Neither study reported live birth rate. Vitrification was associated with an increased clinical pregnancy rate compared to slow freezing (RR 3.86, 95% CI 1.63 to 9.11, P = 0.002, 2 RCTs, 106 women, I(2) = 8%, moderate quality evidence). The effect of vitrification compared to slow freezing on ongoing pregnancy rates was only reported in one small study, with inconclusive findings (RR 6.07, 95% CI 0.86 to 43.04, P = 0.07, one RCT, 28 women, low quality evidence).No data were reported on adverse effects, nor were any other outcomes reported in the included trials. The evidence was limited by imprecision. We assessed the included studies as at low to unclear risk of bias as the methods were not well described.

AUTHORS’ CONCLUSIONS:
Oocyte vitrification compared to slow freezing probably increases clinical pregnancy rates in women undergoing assisted reproduction. However, the total number of women and pregnancies were low and the imprecision is high which limits applicability. The effect on ongoing pregnancy is uncertain as data were sparse. No data were available on live births or adverse effects.

Sources and more information

Cancer Prevention and Safer Chemicals: EDC’s Dirty Dozen 2/3

EWG’s Dirty Dozen: Cancer Prevention Edition 2/3, 2015

EWG_DD_CancerTips-2 infographic
EWG’s Dirty Dozen: Cancer Prevention Edition 2/3

Scientists are only beginning to investigate how certain chemicals may interact to contribute to cancer development. But given that we live in a sea of chemicals, it makes sense to begin reducing exposures to ones we know are bad actors.

Here are EWG‘s tips for avoiding 12 harmful chemicals that have now been found to also disrupt cancer-related pathways — known as cancer hallmarks.

Image sources

  • EWG’S DIRTY DOZEN: CANCER PREVENTION EDITION,
    ewg research, AUGUST 6, 2015.
Related posts and videos

DES may suppress gene important to normal female reproductive tract development

Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis

de-regulation-of-Wnt7a
Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus. Image dev.biologists. Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis.

1998 NIH News Release

Exposure to a synthetic estrogen-like hormone, Diethylstilbestrol (DES), during a critical gestational period appears to suppress a gene that controls reproductive tract development in mice causing changes in the uterus and vagina that are similar to those found in women exposed to DES before birth.

Scientists at the Mt. Sinai School of Medicine, New York City, found that defects in the reproductive tracts of mice exposed in utero to DES are similar to those in mice missing the Wnt7a gene, one of a family of genes that regulate cell interactions in the development of the body and specific organs in living organisms from fruit flies to humans.

Between 1947 and 1971 over 1,000,000 American women were exposed to DES when their mothers took the drug during pregnancy to prevent miscarriage. Women exposed to DES during the first three months of in utero development often exhibit changes in the tissue and/or structure of their uterus, cervix, or vagina. These changes resulted in later infertility problems and also place them at risk of developing a rare form of cancer, clear cell adenocarcinoma of the vagina or cervix, at a young age.

These animal studies should greatly enhance our understanding of the molecular effects of DES exposure, and possibly that of other estrogenic compounds, whether found in the environment or used for medical treatment,” explained Dr. Francis Bellino, Acting Associate Director of the Biology of Aging Program at the National Institute on Aging (NIA). Because the risk of uterine cancer increases with age, the NIA is interested in understanding the molecular response to estrogen and estrogen-like substances used to treat menopause or to prevent breast cancer and how they may contribute to this risk.

These results were reported in the November 1998 issue of the journal, Nature Genetics. The study, conducted by David A. Sassoon, Ph.D., Cary Miller, and Karl Degenhardt, at Mt. Sinai’s Brookdale Center for Developmental and Molecular Biology, was supported by the National Institute on Aging, the National Institute of Dental and Craniofacial Research (NIDCR), and the National Institute of General Medical Sciences (NIGMS).

Initially, the scientists exposed pregnant mice to 200 micrograms/day of DES suspended in sesame oil or to the oil alone on days 15 to 18 of their pregnancy. Samples of reproductive tract tissue from the resulting DES-exposed female offspring were compared to similar samples from Wnt7a mutant mice and the control group. As compared with the control mice, both the DES mice and the Wnt7a group showed similar changes in the epithelium (outer layer of tissue), stroma (the underlying tissue), and the smooth muscle in their uteri. These similarities suggested that Wnt7a was involved in the DES response. In fact, they saw that DES exposure blocks the expression of Wnt7a in the uterus during a time period critical to uterine development in mice. Although expression of Wnt7a does return to normal 5 days after birth, irreversible changes in the organization of the reproductive tract have already occurred.

The scientists also observed structural changes in the reproductive tracts of DES-treated and Wnt7a mutant mice including poorly formed oviducts and vaginal fornices (the area in the vagina near the cervix), as well as hardened areas and abnormal glandular material in the vagina.

Sources and more information
  • DES (Diethylstilbestrol) May Suppress Gene Important To Normal Female Reproductive Tract Development, NATIONAL INSTITUTES OF HEALTH, October 26, 1998.
  • Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis, Nature Genetics 20, 228 – 230 (1998), doi:10.1038/3027, 01 November 1998.
More DES DiEthylStilbestrol Resources

When a family is torn apart by an addiction to prescription drugs

How Prescription Pain Meds Can Destroy Lives – SLLiP Film.

Cam Mitchell is a blue collar young father injured at work who fights to shield his family from his daily pain and addiction to prescription drugs.

More information
    • Written by its lead actor, Ricky Russert, the 25-minute film depicts how prescription pain meds can destroy lives – not only the life of the person who develops an addiction to the meds, but the lives of his family members, as well.
    • SLLiP, vimeo/ondemand, from Ricky Russert, October 17, 2015.
    • How Prescription Pain Meds Can Destroy Lives – SLLiP Film, breakingthecycles, November 8, 2015.
    • More prescription drugs side effects videos on our YT channel.

 

Cancer Prevention and Safer Chemicals: EDC’s Dirty Dozen 3/3

EWG’s Dirty Dozen: Cancer Prevention Edition 3/3, ewg research, AUGUST 6, 2015.

EWG_DD_CancerTips-3 infographic
EWG’s Dirty Dozen: Cancer Prevention Edition 3/3

Scientists are only beginning to investigate how certain chemicals may interact to contribute to cancer development. But given that we live in a sea of chemicals, it makes sense to begin reducing exposures to ones we know are bad actors.

Here are EWG‘s tips for avoiding 12 harmful chemicals that have now been found to also disrupt cancer-related pathways — known as cancer hallmarks.

Image sources

  • EWG’S DIRTY DOZEN: CANCER PREVENTION EDITION,
    ewg research, AUGUST 6, 2015.
Related posts and videos

Some men are at a significantly greater risk of developing breast cancer

Why men – and especially DES Sons – should check themselves for breast cancer

Bill-Becker-by-David-Jay
Breast cancer cases in men are on the rise. Could this be linked somehow to the fact that DES Sons are getting older? Image The SCAR Project: Male Breast Cancer, Bill Becker by David Jay.

Men who carry a specific genetic mutation known as BRCA2 are at significantly greater risk of developing breast cancer than men who don’t carry it. Other things that put men at a greater risk of developing breast cancer are previous radiotherapy to the chest, sex hormone dysfunction, being older and having a close relative with the disease.

Most men are not aware of their own risks while breast cancer cases in men are on the rise. Could this be linked somehow to the fact that DES Sons are getting older?

So what can men do? Physical checks can be much more effective in men because they have a smaller amount of breast tissue. Men should get in the habit of self-examination. See breast self-exam: horizontal techniques for male chest exams.

Read Why men should check themselves for breast cancer, independent, 3 November 2015.

Glyphosate: call to the European Commissioner for Health and Food Safety

Glyphosate – Need for a robust and credible scientific assessment of carcinogenicity

European NGOs joined forces and sent a letter to the Health Commissioner Andriukaitis last Friday asking for an immediate ban of glyphosate.; need for a robust and credible scientific assessment of carcinogenicity.

Organisations across ‪‎Europe‬ have called on the European Commission to adopt the precautionary principle and ban the use of ‪‎glyphosate‬ due to its potential to cause ‪‎cancer‬.

The Commission has a responsibility to protect its citizens from the potential harm that pesticides can cause and given the scientific lack of consensus that glyphosate is not harmful and the recent WHO classification of glyphosate as a probable human carcinogen it is in the interests of the citizens of Europe that its use be stopped with immediate effect.

Read the letter which has been sent to the European Commissioner for Health and Food Safety: Glyphosate – Need for a robust and credible scientific assessment of carcinogenicity, pan-europe PDF. 29 October 2015.

Read UK charity call for partial glyphosate ban and more research on its carcinogenicity.

Pharma industry pushing for a First Amendment right to market its drugs for off-label uses

Drugs, Greed and a Dead Boy

drugs-and-marketing image
The recent court decisions could erode the F.D.A. approval process — put in place to protect the public — and threaten public health and patient safety,” warns Dr. Margaret Hamburg, until recently the Food and Drug Administration’s commissioner.

Children with emotional or mental disorders have become a gold mine for the drug industry. Psychiatric medicines for children account for billions of dollars in sales annually, and the market has boomed.

And now the industry is getting even greedier. It is pushing for a First Amendment right to market its drugs for off-label uses… …pharmaceutical executives see it as a tool to market drugs for unapproved uses.

In a recent column, I recounted how Johnson & Johnson deceptively marketed an antipsychotic medicine called Risperdal, concealing for example the fact that it can cause boys to grow large, pendulous breasts (one boy developed a 46DD bust). J&J got caught, pleaded guilty and paid more than $2 billion in penalties and settlements — but also registered $30 billion in Risperdal sales. The executive who oversaw this illegal marketing effort was Alex Gorsky, who then was promoted to chief executive of J&J. If you’re a pharmaceutical company, crime sometimes pays.

Read Drugs, Greed and a Dead Boy and When Crime Pays: J&J’s Drug Risperdal, on NYtimes, by Nicholas D. Kristof.

See study National Trends in the Office-Based Treatment of Children, Adolescents, and Adults With Antipsychotics, Arch Gen Psychiatry. 2012;69(12):1247-1256. doi:10.1001/archgenpsychiatry.2012.647, JAMA Dec 2012.

See Embracing 21st Century Information Sharing: Defining a New Paradigm for the FDA and Communications with Health Care Professionals, Food and Drug Law Journal, 2015.

DES exposure and the aging woman: mothers, sons and daughters

Increased risk of cancers for the DES-exposed

image of holding hands
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.

2002 Study Abstract

Diethylstilbestrol (DES), the first orally active artificial estrogen ever developed, was prescribed to several million pregnant women during the 1940s through the 1960s in the mistaken belief that it reduced the risk of miscarriage.

In 1971, the US Food and Drug Administration contraindicated its use in pregnancy when DES was associated with the development of vaginal clear cell adenocarcinoma (CCA) in daughters exposed in utero.

In daughters whose mothers took DES during pregnancy, the drug has been associated with congenital malformations of the reproductive tract, fertility problems, a possible increased risk of cervical carcinoma in situ, and a presumed lifetime risk of vaginal and cervical CCA.

DES mothers have an increased risk of breast cancer (RR = 1.3).

DES sons have an increased prevalence of urogenital anomalies, and a possible increased risk of testicular cancer.

Sources and more information
  • DES exposure and the aging woman: mothers and daughters, Current women’s health reports, NCBI PMID: 12215312, 2002 Oct;2(5):390-3..
More DES DiEthylStilbestrol Resources