Tag Archives: diethylstilbestrol

DES on Lifetime’s “The Conversation” Website!

1 Aug

WONDER DRUG screenwriter Caitlin McCarthy’s piece “I’m A DES Daughter. Are You?” just went live today on the website for Lifetime’s “The Conversation with Amanda de Cadenet” (the show being heralded as the new Oprah). Kindly check out her piece and leave a comment underneath it: www.theconversation.tv/wellness/im-a-des-daughter-are-you/

Tomorrow is the Deadline for DES Activist’s Citizens Medal Nomination!

23 Apr

Tomorrow (April 24) is the last day to write and/or Tweet the White House about the Presidential Citizens Medal.

As you know, for the 2nd year in a row, DES Daughter Caitlin McCarthy has been nominated for a Presidential Citizens Medal for her DES activism. 

If you have not already done so, here is your opportunity to help support what Caitlin is doing to further the cause for the DES exposed. THAT helps all of us!

Because of Caitlin’s activism and joint efforts with the offices of US Senator John Kerry (D-MA) and US Senator Scott Brown (R-MA), the FDA finally acknowledged DES as a “tragedy” in 2011 after 40 years of silence.

In a further effort to educate, enlighten, and inspire others about DES, Caitlin has written an award-winning feature screenplay called WONDER DRUG, now in development with producer/star Alysia Reiner. Caitlin also speaks on TV, in print media, and on panels about DES – all while working as an urban public high school English Language Arts teacher in Worcester, MA, a high need school district.

The Presidential Citizens Medal is the second highest civilian award in the United States, second only to the Presidential Medal of Freedom.

If you would like to express your support of Caitlin McCarthy’s nomination for a 2012 Presidential Citizens Medal, please Tweet the following to the White House (@whitehouse): “I support DES Daughter Caitlin McCarthy (@CaitlinMcWriter)’s nomination for a 2012 Presidential #CitizensMedal!”

You can also send a message of support via this webform to the White House HERE.

Your message can read: “I support DES Daughter Caitlin McCarthy’s nomination for a 2012 Presidential Citizens Medal for her DES activism. Because of Caitlin’s activism and joint efforts with the offices of US Senator John Kerry (D-MA) and US Senator Scott Brown (R-MA), the FDA finally acknowledged DES as a “tragedy” in 2011 after 40 years of silence. In a further effort to educate, enlighten, and inspire others about DES, Caitlin has written an award-winning feature screenplay called WONDER DRUG, now in development with producer/star Alysia Reiner. Caitlin also speaks on TV, in print media, and on panels about DES – all while working as an urban public high school English Language Arts teacher in Worcester, MA, a high need school district. Thank you for your consideration.”

WONDER DRUG HAS AN OSCAR-NOMINATED DIRECTOR!

16 Feb

Academy Award® nominated director Joan Stein Schimke has joined the team of producer/star Alysia Reiner (www.alysiareiner.com) and screenwriter Caitlin McCarthy (www.caitlinmccarthy.com) on WONDER DRUG, a feature film now in development.

Winner and nominee in over 20 international film festival screenplay competitions and labs, including the prestigious Hamptons Screenwriters Lab as an Alfred P. Sloan Foundation script, WONDER DRUG is inspired by the true story of DES (diethylstilbestrol), a toxic, carcinogenic drug seen as a medical miracle to help women with pregnancy issues and a cash cow for pharmaceutical companies upon its creation.

Joan was nominated for an Academy Award® for her short film ONE DAY CROSSING. The film, shot in Hungary, won several other awards including the Student Academy Award® Gold Medal, the Director’s Guild of America (DGA) Best Woman Student Filmmaker, and Best Director, National Board of Review.

Her short film SOLIDARITY screened at over a dozen festivals, including the New York Film Festival and the Expresion en Corto Film Festival, where it was awarded Best Short.

Other directing credits include “Law and Order” and the short films CITY MINUTES, FAULT LINE and REAP THE WHIRLWIND. Joan has worked as the Production Coordinator on Eric Mendelsohn’s 3 BACKYARDS (Winner: Best Director, Sundance Film Festival; starring Edie Falco); as Locations Coordinator on Woody Allen’s DECONSTRUCTING HARRY; and as an assistant to Director Bette Gordon on the feature LUMINOUS MOTION. She was invited to be mentored by Director Taylor Hackford on the set of RAY starring Academy Award® winner Jamie Foxx.

Joan is an Associate Professor at Adelphi University and is currently developing several film projects.

For more information on WONDER DRUG, please visit www.wonderdrugthemovie.com and www.facebook.com/wonderdrugthemovie.

Full bios on Alysia and Caitlin can be found below.

###

WONDER DRUG PRODUCER/STAR ALYSIA REINER:

Alysia is an award winning actress, producer, mother, humanitarian, and outspoken environmentalist.

As an actress, Alysia won a Screen Actors Guild Award (Outstanding Performance for an Ensemble Cast) playing Christine, Jack’s fiancee and then bride, in the Oscar-winning film “Sideways.”. Alysia’s other film credits include “Backwards”, “Not For Nothing”, Arranged”, “Kissing Jessica Stein,” “One Last Thing,” “The A List,” “For Love of the Game” with Kevin Costner, “Row Your Boat” with Jon Bon Jovi, “The Narrow Gate,” “Hourly Rates,” “3 Body Problem,” and “The Stand In.” Most recently, “The Vicious Kind”, produced by Neil LaBute, premiered at Sundance 2009, was nominated for two independent Spirit Awards.

Among her many stage roles, she starred in the New York Premiere of “Pentecost” by Tony-winning playwright David Edgar, and starred in the provocative two character play “An Oak Tree” with Tim Crouch, which won a Special Obie Award. Her portrayal of June Miller in “Anais Nin: One Of Her Lives” was critically acclaimed, as was her turn in “Wasps In Bed” at The Beckett Theater, of which the New York Times wrote “Alysia Reiner is priceless.” Last summer she originated the role of Tina Modotti in “Modotti”. Other New York theater includes “Hillary: A Modern Greek Tragedy With A Somewhat Happy Ending” at The Public Theater, “Jayson With a Y,” “Manhattan Cassanova” with Mercedes Ruehl, and “Love in the Age of Narcissism” and “Dating Games,” both with her husband, actor David Alan Basche.Alysia has appeared on stages around the country; from the Sundance Filmmakers Lab in Utah to The Matrix Theatre in LA to The Forum Theater in New Jersey; and around the world from The Edinburgh Festival in Scotland to The Royal Court Theatre in London. This Fall she starred in the US premiere of A CHARITY CASE Off-Broadway.

Alysia’s many TV roles include “Blue Bloods,” “The Sopranos,” “Law & Order” (all 3 shows), “30 Rock,” “White Collar,” “Love Monkey,” “The Drew Carey Show,” “The Practice,” “The Jury,” “Family Law,” “Jack & Jill,” and series lead in the pilot “An Englishman in New York.”

Speed Grieving, the short film that Alysia created, produced and stars in, had it’s World Premiere at The Hamptons International Film Festival, and has since been invited to over a dozen more film festivals and has won multiple awards. She has been asked to be a regular contributor – about grief & and film – for the Huffington Post and Maria Shriver’s Website.

As a new mother, she was featured on Celebrity Baby Scoop, Stroller Traffic, People.com, Healthy Child Healthy World, Family Focus Blog, Today I ate a Rainbow, Your Green Baby, and others. She is a celebrity green momma spokesperson for Best For Babes, an organization that works to change how we view and support breast feeding, and gives moms the solutions they need to make it work.

Alysia is a champion of all things eco-friendly, and she and her husband recently used their own home as a way to share information about building green. Their brownstone renovation in Harlem was featured on television’s “World’s Greenest Homes” and “Renovation Nation”; in various magazines like Dwell, Gotham, and The Nest; and they allowed the environmentally friendly construction process to be chronicled on Web sites such as Dwell.com and Kohler.com.

She was recently recognized as an INTELLIGENT OPTIMIST in Ode Magazine:
http://www.odemagazine.com/blogs/intelligent_optimists/22336/alysia_reiner
and profiled by New York Women in Film and Television as a woman to watch:
http://www.nywift.org/article.aspx?id=2319.

Alysia is on the board of The Broad Collective, and is involved with many charities including The Cancer Support Community, Habitat for Humanity, Our Time Theatre Company, 52nd Street Project, Actors for Autism, Joyful Heart Foundation, Comp2Kids, GEMS, and Circle of Health International.

For more information:

twitter: @alysiareiner

www.facebook.com/SpeedGrieving

http://www.facebook.com/AlysiaReiner

www.speedgrieving.org

www.alysiareiner.com

WONDER DRUG SCREENWRITER CAITLIN MCCARTHY:

Caitlin McCarthy received her Master of Fine Arts in Creative Writing from Emerson College, which is ranked by U.S. News & World Report as one of the best graduate programs in the country. An award-winning screenwriter at international film festivals and labs, Caitlin has two feature films in development: WONDER DRUG with producer/star Alysia Reiner and director Joan Stein Schimke; and RESISTANCE with Populus Pictures and director Si Wall. In addition to screenwriting, Caitlin serves as an English teacher at an inner-city public high school in Massachusetts. Prior to education, Caitlin worked in public relations, where she fostered relationships with the press and crafted messages for companies that were delivered worldwide.

Awards and Nominations

Caitlin was nominated for a 2011 Presidential Citizens Medal for her work on the DES (diethylstilbestrol) issue.

IMAGINE Magazine named Caitlin a “Woman to Watch” in 2011.

The Pulse Magazine named Caitlin one of the “People to Watch in 2011.”

Caitlin was a 2008 Fellowship Grant Recipient from the Worcester Arts Council (WAC), formerly known as the Worcester Cultural Commission. WAC falls under the umbrella of the Massachusetts Cultural Council.

She was also a finalist for the 2011 Artist Fellowships Program of the Massachusetts Cultural Council (MCC), receiving a financial award.

Caitlin’s writing has collectively won awards and nominations in over 60 international film festival screenplay competitions and labs, most notably:

** WONDER DRUG: Selected as an Alfred P. Sloan Foundation script for the Hamptons Screenwriters Lab and chosen for a live staged reading of select scenes at the 15th Annual Hamptons International Film Festival, sponsored by the Sloan Foundation. Reading starred Steve Guttenberg (THREE MEN AND A BABY) and Alysia Reiner (SIDEWAYS). Also winner of the “Most Likely To Be Produced” screenplay award at the 2010 Action on Film International Film Festival. Currently in development with actor/producer Alysia Reiner and director Joan Stein Schimke.

** RESISTANCE: Winner of the Atlanta Film Festival’s Inaugural Screenplay Competition. The prize for winning was participation in a weekend retreat with a group of renowned writing, directing, and producing mentors. Caitlin’s mentors were Joy Lusco Kecken (NBC’s “Homicide” and HBO’s “The Wire”) and Michael Lucker (VAMPIRE IN BROOKLYN). Currently in development with Populus Pictures and director Si Wall.

** FREE SKATE: Winner of the MTV/WIF TV & Media Outreach Program. The top ten applicants presented their ideas directly to senior members of MTV’s development team on a designated pitch day in June of 2010. Caitlin pitched FREE SKATE as a scripted series. Currently in the process of being optioned by an LA-based production company.

** CAPE COD LITE: Winner of the “Best Drama” screenplay award at the Action on Film International Film Festival. A five-minute scene was shown as a “mini-movie” during the festival. Currently at script stage.

** PASS/FAIL: First Place – Best Short Script in the 2011 RIIFF (Rhode Island International Film Festival) Screenplay Competition. Pilot teleplay also selected for interpretation on camera by the Action on Film International Film Festival. A five-minute scene was shown as a “mini-movie” during the festival. Currently at script stage.

For more information, visit www.caitlinmccarthy.com.

Email WCVB-TV Boston about DES Segment

8 Jan

WCVB-TV Boston "Chronicle"

Ask WCVB-TV Boston’s “Chronicle” newsmagazine to re-air its June 3, 2011 segment about DES before the DES breast cancer cases hearing on January 19, 2012. Send your request to: chronicle@TheBostonChannel.com

Press Release About DES Breast Cancer Cases in Boston, MA

15 Sep

FOR IMMEDIATE RELEASE

 

DISTINGUISHED HARVARD EPIDEMIOLOGIST TESTIFIES AGAINST ELI LILLY & COMPANY AND BRISTOL-MYERS SQUIBB THAT DES DAUGHTERS ARE AT SUBSTANTIAL RISK FOR BREAST CANCER

On September 7, 2011, in the United States District Court for the District of Massachusetts in Boston, Dr. Hans-Olov Adami, former Chair of the Harvard School of Public Health, Department of Epidemiology and a world-renowned physician and epidemiologist, testified that women exposed in utero to diethylstilbestrol (DES) are at substantially increased risk for breast cancer.  Dr. Adami cited to Dr. Julie Palmer’s 2006 NCI study, “Prenatal Diethylstilbestrol Exposure and the Risk of Breast Cancer,” which showed a 2.05 – 3.85 relative risk for DES daughters over the age of 40.  Dr. Adami “found it overwhelmingly likely based on this methodology that DES causes breast cancer, [and] increases substantially the risk of breast cancer in women starting about the age of 40.”

In confirming the Palmer study in court as a valid and important reopening of the never-ending DES tragedy, Dr. Adami stated: “so the bottom line of this is it provides strong evidence that DES exposure increases the risk, and that the risk increase starts sometime around age 40 and then grows as women get older.”

Dr. Adami stressed that there are two practical implications in the Palmer study: “one is that it reinforces the importance of women who have been exposed to participate in mammography screening programs in order to allow early detection of breast cancer if they develop it; and secondly, because women who have been on hormone replacement therapies are already at an increased risk, the indications should be very restrictive to add another major risk factor if they have also been exposed to DES in the uterus.”

DES, primarily promoted by Eli Lilly and Company and E.R. Squibb & Sons (the predecessor to Bristol-Myers Squibb) was given to two to five million pregnant women in the 1950’s and 1960’s and was banned in 1971 when it was discovered to cause cancer and malformations of the reproductive tract.  Massachusetts Governor Deval Patrick recently declared “DES Awareness Week” this July commemorating the experience of DES daughters and warning of breast cancer risks.

The trial taking place in federal court will continue for another week and a half as the fifty-three DES daughters involved put on further biology, toxicology, oncology, and obstetrics and gynecology experts to support Dr. Adami’s opinion of this substantial DES breast cancer risk in the daughters.

For Further Information, Contact:

Aaron M. Levine & Associates

1320 19th St., NW

Fifth Floor

Washington, DC 20036

(202) 833-8040

aaronlevinelaw@aol.com

Latest DES Breast Cancer Cases Update

13 Sep

The transcript for the DES breast cancer cases is considered public record, so the following info can be shared without compromising anything.

The past Chair of the Harvard School of Public Health said on Day 2 that overwhelming evidence shows that DES exposure causes breast cancer.
Below are some notable quotes in the transcript:
  • P. 31: (starting at line 13)  “… so the bottom line of this is it provides strong evidence that DES exposure increases the risk, and that the risk increase starts sometime around age 40 and then grows as the women grow older.”
  • p.34: (starting at line 13) “… you can conclude that this is the most powerful design we have in epidemiology…”
  • p.35 (starting at line 9): “… I found it interesting and reassuring that no one has pinpointed any sort of bias in the Palmer study in all of the documents I have read.”
  • p. 44 (starting at line 19 ): “… two practical implications: one is that it reinforces the importance of women who have been exposed to participate in mammography screening programs in order to allow early detection of breast cancer if they develop it; and secondly, because women who have been on hormone replacement therapies are already at an increased risk, the indications should be very restrictive to add another major risk factor if they have also been exposed to DES in the uterus.”
  • p.56 (starting at line 2): “…so in my interpretation this indicates strongly that there is, indeed, a dose-response trend between DES exposure and risk of breast cancer.”
  • p. 57 (starting at line 3): “…it’s overwhelmingly plausible that the mechanism exists whereby DES could increase the risk of breast cancer in humans.”
  • p. 21 (starting at line 21): “… I found it overwhelmingly likely based on this methodology that DES causes breast cancer, increases substantially the risk of breast cancer in women starting about the age of 40.”
  • p. 61 (starting at line 1): “But once she has contracted the disease, we can say that there’s a 75% probability that the disease developed due to DES exposure.”
If you would like to be emailed a copy of the transcript quoted above, please email your request to diethylstilbestrol@hotmail.com. We’ll send it over to you.

You Heard It Here First — Report from the DES Breast Cancer Cases in Boston

7 Sep

*PLEASE CONTINUE TO CHECK THE DES INFO BLOG SITE AND FACEBOOK PAGE FOR UPDATES*

Opening statements were made today in the case of Fecho et al v. Eli Lilly and Company, and the upcoming proceedings and judge’s ruling will determine whether or not the plaintiffs, all DES daughters with breast cancer, will be able to move forward with their lawsuit.  The case is being considered by Judge Marianne B. Bowler at the John J. Moakley Federal Courthouse in Boston, Massachusetts.  In addition to one of the plaintiffs, a Boston area DES daughter and I were in the courtroom along with about two dozen lawyers representing Big Pharma.  The defendants in the case include:

  • Eli Lilly and Company
  • Abbott Laboratories, Inc.
  • Glaxosmithkline (as successor to Burroughs-Welcome & Co.)
  • Merck & Co., Inc.
  • Pharmacia & UpJohn Company (formerly known as Upjohn Company)
  • Premo Pharmaceutical laboratories, Inc.
  • Aventis Pharmaceuticals, Inc. (a successor to Rhone-Poulenc Rorer Pharmaceuticals, Inc.)
  • Elan Pharmaceuticals, Inc. (as successor to Carnick Labs)
  • Kremers-Urban Company
  • Mallinckrodt, Inc.
  • Ortho-McNeil Lab, Inc.
  • Person & Covey, Inc.

Of note to our readers, Attorney Aaron Levine referenced this year’s DES Awareness Week here in Massachusetts, reading aloud from the text of the DES Awareness Week Proclamation, which was issued to this Admin by the office of the Governor.

Both sides presented their opening statements, with Attorney Levine going first.  Speaking for the defendants were two attorneys representing Eli Lilly.  Aaron Levine put forth sound arguments as to why DES is a contributing factor to breast cancer.  He referred to the Palmer study, which has described the increased risk for this population, as the “eminent study deserving deference.”  Lilly’s attorney called Palmer’s subgroup analysis a “fraud”; the result of “slicing the data of the subgroup very finely” to support their theory that there is “no statistically increased” risk of breast cancer in the DES group studied by Palmer and her colleagues.

A dozen experts will begin testifying tomorrow and will finish some time next week.

FYI, the Docket # for the case is 11CV-10152.  Copies can be obtained from the Court Clerk’s office for a fee.

At the conclusion of the court session today, I and the two other DES daughters got acquainted over lunch. I want to thank the plaintiff for her courage and the local DES daughter for making the time to come to the courthouse and show her support.  My understanding is that there will be a stream of DES daughters in the courtroom throughout the proceedings.  If any of you has the chance to stop by the courthouse and listen for a while, please take a few notes and post your thoughts here at DES Info.

Posted by Admin Andrea


Don’t Forget This Wednesday — Historic DES Breast Cancer Cases in Boston!

5 Sep

Real DES Drug Ad From The 1950s.

Please consider showing your support for the historic DES breast cancer cases by attending the opening statements this Wednesday, Sept.  7th, in Boston. The hearing will likely begin at 9:30 a.m. and go until 4:30 p.m., with lunch in between. The court house is at:

United States District Court for the District of Massachusetts — Boston

1 Courthouse Way

Boston, Massachusetts 02210

(617) 748-9152

Below is a message from  attorney Aaron Levine about the cases:

Our firm is single-handedly presenting the case for 53 DES daughters with Breast Cancer.  We have been fighting for three years now and have put together a team of world renowned scientists who have concluded DES pre-natal exposure causes a significant increase in the risk of Breast Cancer in the  40 years old plus, population.

The drug companies have fought hard and the attached brief sets forth our case against them.   The case will be heard by Judge Bowler in Boston at the John Joseph Moakley Courthouse, Sept 7-23, 2011.  The hearing is open to the public if you would like to attend.

If you want any more information or feel you could help our case in any way, please call Toll Free: 1-888-868-5380.

End Message.

 

 

This Sept. 7th in Boston: Attend Historic DES Breast Cancer Cases!

31 Aug

DES Bottles and Pills

This just in from Aaron Levine:

Our firm is single-handedly presenting the case for 53 DES daughters with Breast Cancer.  We have been fighting for three years now and have put together a team of world renowned scientists who have concluded DES pre-natal exposure causes a significant increase in the risk of Breast Cancer in the  40 years old plus, population.

The drug companies have fought hard and the attached brief sets forth our case against them.   The case will be heard by Judge Bowler in Boston at the John Joseph Moakley Courthouse, Sept 7-23, 2011.  The hearing is open to the public if you would like to attend.

If you want any more information or feel you could help our case in any way, please call Toll Free: 1-888-868-5380.

End Message.

Please consider showing your support by attending the opening statements on Sept.  7th. The hearing will likely begin at 9:30 a.m. and go until 4:30 p.m., with lunch in between. The court house is at:

United States District Court for the District of Massachusetts — Boston

1 Courthouse Way

Boston, Massachusetts 02210

(617) 748-9152

 

 

 

 

 

French DES Report

8 Jul

French DES BottleMany thanks to Pamela Solere (from Réseau D.E.S. France) for sharing a translation of the very important official document, published at the end of June 2011 by the AFSSAPS (the national French Agency for the Safety of Health Products). The original French document can be found at this website: http://www.des-france.org/professionnels-sante/note-info.php#miseaupoint2011

The complete original text is translated as published by the AFSSAPS.

You will of course find specificities that concern France, especially DES being prescribed during pregnancies from 1948 to 1977, which means that the DES Daughters in France are younger than in the US, some being born in 1978.

The doses prescribed were probably not the same as in other countries, but the information about the dangers following the period when DES was prescribed are general.

The AFSSAPS has been in the news recently, because of the Médiator drug scandal. This has lead to changes inside the Agency, imposed by the President of the Republic, to install more transparency and independence (and to calm public protestation). The present text, which was promised by the AFSSAPS doctor who was present at the Paris conference day in November, is very widely based on the Réseau D.E.S. France publication which followed. It is an official text for gynecologists, obstetricians and doctors. A new campaign was essential as so many doctors still think of DES as ancient history… something we all know !

AFSSAPS

Agence française de sécurité sanitaire des produits de santé

French Agency for the Safety of Health Products

Complications related to in utero exposure to diethylstilbestrol (DES)

(Distilbène®, Stilboestrol-Borne®)

2011 Update

Key facts

The problems associated with DES exposure in utero remain current and monitoring of the next generation (children of parents exposed in utero) must continue to assess the multi-generational effects.

The major role of physicians and particularly gynecologists and obstetricians is to:

–          Inform women who may be affected either because of DES drug treatment during their pregnancy, or because of known exposure to DES in utero.

 

–          Consider in utero exposure:

  1. 1.      when taking the medical history of any woman born between 1948 and 1977, whose mother had  miscarriages or obstetrical problems.
  2. 2.      during clinical examinations when there are characteristic vaginal or cervical lesions
  3. 3.      where hysterography shows images suggestive of a T shaped uterus or uterine hypoplasia.

 

–          Routinely explore possible in utero DES exposure in the following clinical situations: a fertility checkup, an ectopic pregnancy, recurrent 1st trimester miscarriages and particularly after any 2nd trimester miscarriage, a premature delivery.

 

–          Refer the patient to a DES knowledgeable specialist and arrange for appropriate monitoring when DES exposure is known or suspected.

 

–          In principle, consider the pregnancy of a women who has been exposed to DES in utero as  a high risk pregnancy

 

Patients exposed to DES have a crucial role in handing down the “record” of their exposure to the next generations to allow continued adequate monitoring and implementation of appropriate treatment and care.

Historical facts

Diethylstilbestrol (DES), a non-steroidal synthetic estrogen, was prescribed in France between 1948 and 1977, under the trade names Distilbène® and Stilboestrol-Borne® for pregnant women in order to prevent miscarriages, bleeding, as well as other complications during pregnancy such as preeclampsia or pregnancy diabetes.

It is in the USA in 1971 that the first cases of vaginal cancer were discovered among daughters exposed in utero to DES. One of the first French cases of vaginal adenocarcinoma among young girls was published in 1975. In France the indication “repeated miscarriages” was withdrawn in 1976 and the contraindication for pregnant women was added in 1977.

Since then, other genital and obstetrical complications associated with in utero exposure have been observed and have been successively published, including in brochures distributed to health professionals and then to the general public.

Diethylstilbestrol (DES) is currently marketed under the name Distilbène®, but its only indication is during the medical treatment of prostate cancer.

Current issues

The problems associated with in utero DES exposure are still current and probably will remain so for years to come. Indeed, between 1948 and 1976, approximately 200,000 women in France were treated with DES during their pregnancies, with a peak of prescriptions at the end of the 1960’s and beginning of 1970’s. Taking into account the miscarriages and fetal and neonatal deaths, the number of children born from these pregnancies is estimated at 160,000 (that is 80,000 daughters and 80,000 sons exposed in utero to DES). The patients exposed in utero are now between 33 and 63 years old, and  monitoring the effects of DES exposure for them must continue for years to come, as well as for the children of this population to evaluate the multi-generational impacts.

New scientific information is available since the first DES warning Bulletin was published in January 1983, prepared in collaboration between the association Réseau D.E.S. France and the Affsaps (French Agency for the Safety of Health Products).

Moreover, a recent Afssaps survey among gynecologists revealed that only half of them knew precisely all the adverse effects of DES exposure and that 40% of them hoped that a new information campaign will be organized.

As a result, the Affsaps has decided to update their information Bulletin and to undertake an awareness campaign among health professionals about the methods of DES screening and the follow-up protocols for these patients.

 

What are the risks associated with an in utero exposure to DES ?

The risks of genital damage after DES exposure depends mainly on the period of exposure to the drug treatment rather than its duration or doses. The identified period of risk is between the 6th and 17th week of gestation.

The main established complications that are known are :

For a daughter:

–          Clear cell adenocarcinoma of the vagina and cervix with an occurrence rate of  approximately 1 case per thousand patients exposed in utero. An adenocarcinoma has been diagnosed among women aged between 7 and 49 years old, with an average age of 24 ½ years. The declared cases of uterine and vaginal cancers among DES exposed women have considerably decreased since 2005.

**Nevertheless, it is important to continue medical supervision and to note that the proportion of vaginal cancers is diminishing, whereas the number of cervical cases is increasing.

–  Structural, morphological and functional abnormalities of the vagina, cervix and fallopian tubes. In order of frequency they are:

– Adenosis (cervico-vaginal ectopy of the cylindrical mucous membrane): presence of the cylindrical cervical mucus outside its normal localization. This is observed in about 30% of exposed young women with no symptoms, and in 60% of exposed young women with specific clinical indications. Generally the recovery is spontaneous. The adenosis lesion is likely to bleed and become infected and can be made worse by abusive cervical treatment interventions (coagulation, cryotherapy and laser);

– Other cervico-vaginal anomalies (20% to 60% of the young exposed women): structural cervical and vaginal anomalies can be observed. The most frequent is cervical hypoplasia (absence or small tip of the cervix, a ‘crest of helmet’ appearance);

– Anomalies of the uterus: often associated to the former anomalies with, by decreasing order of frequency: a T shaped uterus and small uterine cavity, uterine hypoplasia (uterus globally small), narrowing of the uterine cavity (pseudosynechia), strictures, uterine diverticula;

– Anomalies of the fallopian tubes: particularly narrow tubes, as observed by laparoscopy.

– Some of these affects can cause fertility problems (for about one out of three women exposed) and obstetrical complications:

ovulation problems : risk of premature ovarian failure (POF), according to observations, but not yet confirmed

cervical problems with anomalies of the cervical mucus, making sperm penetration difficult

ectopic pregnancies : the risk, compared to the general population, is multiplied 5 or 10 fold, according to different surveys

early miscarriages (during the 1st trimester) : slightly more frequent than in the general population

late miscarriages from 15 to 24 weeks gestation : particularly characteristic among these patients, with 10 times the risk compared to the general population

premature births : related to uterine anomalies

postpartum hemorrhage : the risk is increased in the DES exposed population.

It is to be noted that the percentage of term delivery is 84% for the general population, compared to 50% for DES exposed women, and only 33% for DES exposed women with a morphological genital anomaly.   

For the medical care and treatment of genital anomalies in DES exposed women, the following have been suggested:

– Hysteroplasty for enlargement of the uterine cavity with the objective of improving fertility and reducing the risks of recurrent miscarriages. This surgical procedure is not the first-line of management (2003 ANAES recommendations), as its efficacy and safety are not well assessed

– Cervical cerclage in the case of a high risk of late miscarriage or premature birth (with previous history of this type of dysfuncion, or uterine or cervix malformation such as hypoplasia), to be considered on a case by case basis.

For a son:

The adverse urogenital effects of DES exposure in utero for a son are more frequent than in  the general population, and include epididymal cysts, testicular abnormalities such as hypotrophy of the testes, cryptorchidism, capsular induration and abnormal position of the urinal meatus (hypospadias).

Beyond the known complications of in utero exposure:

Different publications have issued warnings of the risk of breast cancer for DES daughters exposed in utero but the results of the studies are contradictory. 

An American study suggests an increased risk of breast cancer among women DES exposed in utero more that 40 years old, with a dose-effect relationship. However, a recent European study does not indicate a significant increase in this risk.

Confronted with these contradictory elements, Afssaps has asked a group of expert epidemiologists to analyze the available information and give their recommendations concerning the relevance of specific supervision measures for in utero exposed women. The benefits from mammography screening must be weighed against the risk from X-ray exposure after repeated mammograms.

Patient groups have raised concern about possible occurrence of post-adolescent psychiatric disorders but the study undertaken by Afssaps has not confirmed this risk

Afssaps implemented and funded a study in 2002, coordinated by the Inserm (National health and medical research institute), with a cohort of 1,352 mothers, members of the teachers’ health service, and who were DES exposed during at least one of their pregnancies. The study compared the occurrence of recognized serious adult psychiatric disorders (psychiatric hospitalization, suicide) among brothers and sisters exposed with those non-exposed to DES in utero, or to progestagens or other hormones. The same results were observed for psychiatric disorders as defined on a broad level, grouping together serious recognized psychiatric disorders as well as medical consultations for psychiatric symptoms.

Recently, results of a USA group study published in “Nurse Health Study”, suggest an increase in depression risk associated with DES in utero exposure, but there exists a bias notably concerning the method of collecting data on DES exposure and concerning the depressive problems, which limits the validity of these results.

Some patients remain strongly concerned on this matter, and so Afssaps later this year plans to conduct a public hearing for these groups and their experts to reexamine their facts.

What are the risks  for the children of parents exposed to DES in utero ?

The problems observed among the children of mothers exposed in utero are mainly related to the complications associated with premature births.

In addition, certain epidemiological studies, including Dutch and French, have reported an increased risk of hypospadias for sons whom mothers have been exposed to DES in utero. As a result, a study has been undertaken by Afssaps, coordinated by the Paris hospital teams (Assistance Publique – Hopitaux de Paris) and by the Inserm (National health and medical research institute) for all the DES in utero exposed women having given birth to a son between 1996 and 2008 in the Saint-Vincent-de-Paul maternity hospital in Paris. For now, the identification of cases of hypospadias in the 3rd generation of DES exposed families underlines the necessity to continue monitoring the multi-generational risks of urogenital malformations.

To date, there is no evidence of genital anomalies for the daughters of in utero exposed mothers. However, further studies are necessary to confirm these results.

How to screen for DES exposure ?

In cases where DES exposure is known by the mother or by her daughter:

*Either a mother may reveal that she received DES treatment during one or more of her pregnancies between 1948 and 1977. It is necessary to inform her of the possible consequences for her children and to advise her to send them, particularly if they are daughters, to a DES knowledgeable specialist for routine medical follow-up.

*Or a young woman, knowing her DES in utero exposure, consults for a gynecological or obstetrical reason. It is necessary to inform her of the risks and to refer her to a DES knowledgeable specialist for routine medical follow-up.

In cases where exposure is unknown:

Confirmation or indicators of in utero exposure can be obtained with the following:

1) In questioning a patient born between 1948 and 1977, when learning of the mother’s history of miscarriages or obstetrical difficulties.

2) During clinical examination, discovering cervical or uterine anomalies characteristic of a DES exposure.

3) With hysterography, when the images show signs of a DES exposure.

*Moreover, for all women born before 1977, a DES exposure must be routinely explored in the following clinical situations:

– ectopic pregnancies

– recurrent 1st trimester miscarriages, and particularly 2nd trimester miscarriages

– premature births

If DES exposure is suspected, the patient will be referred to a DES knowledgeable specialist for medical follow-up.

 

What is the routine medical follow-up for women DES exposed in utero ?

Even in the absence of any symptom, a yearly consultation with a gynecologist is essential and must include:

 

*a gynecological examination to check any vaginal or uterine anomaly

*vaginal and cervical smears

*a colposcopy pending on the results of the vaginal and cervical smear tests

Unexplained bleeding between menstrual periods must be immediately followed up with a gynecological examination to eliminate any DES complications.

Recommendations for fertility problems of a woman DES exposed in utero

In the case of fertility problems, the medical checkup must include a Huhner test to judge the quality of the cervical mucus, a hysterography to detect an anomaly of the uterine cavity and fallopian tubes and an echography coupled if possible with a Doppler to evaluate the uterine artery pulsatility and thus the possibilities of implanting an embryo.

In all cases, this checkup is included in the general regime for couples with fertility problems.

What pregnancy care for a woman DES exposed in utero ?

Every pregnancy for a woman DES exposed in utero must be considered, in principle, a high risk pregnancy, even if in many cases it continues normally.

It is recommended that these women be informed of the increased risk of ectopic pregnancies, early and late miscarriages, and premature births, often without feeling contractions.

It is therefore necessary to check on the intra-uterine status of the embryo and to do two-weekly cervical checks.

Preventive measures: resting, reducing activity, stopping work, midwife follow-up at home, possibility of hospitalization – these measures will vary according to the obstetrical history, detected uterine anomalies, and condition and progress of the cervix.

In general, early resting is recommended as the risk of prematurity is approximately the same as for a twin pregnancy. Resting is one of the main factors in preventing miscarriages and prematurity. The French National Health Service has organized exceptional maternity leave (*) for pregnancies related to an exposure to Distilbène®.

Cervical cerclage may be indicated in certain cases.

 

 

(*)http://www.ameli.fr/employeurs/vos-demarches/conges/le-conge-maternite/grossesse-pathologique-liee-au-distilbene.php

Patient associations :

 

Réseau D.E.S. France

Centre administratif,

1052, rue de la Ferme de Carboué,

40000 MONT-DE-MARSAN

Tél. 05 58 75 50 04

www.des-france.org

 

Les filles DES

56, boulevard Pasteur,

94260 FRESNES

www.lesfillesdes.com

 

HHORAGES

7, allée des Dahlias,

93700 DRANCY

www.hhorages.com

 

 

 

 

Centres Régionaux de Pharmacovigilance et Centre de Renseignement sur les Agents Tératogènes

(for the references of the regional pharmacovigilance centers, consult the Afssaps site : http://afssaps.fr)

 

Bibliographical references

ANAES. « Evaluation de l’hystéroplastie d’agrandissement dans le traitement des anomalies utérines secondaires

à l’exposition au diéthylstilbestrol ». 2003

 

Brouwers MM, Feitz WFJ et coll. “Hypospadias: a transgenerational effect of diethylstilbestrol?” Human Reprod

2006; 21(3):666-9.

 

Hatch EE, Palmer JR et coll. “Cancer risk in women exposed to diethylstilbestrol in “utero”. JAMA 1998;

280(7):630-4.

 

Kalka N, Paris F et coll. « Prevalence of hypospadias in grandsons of women exposed to diethylstilbestrom during

pregnancy : a multigenerational national cohort study ». Fertil Steril In press.

 

Klip H, Verloop J et coll. “Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study”

The Lancet 2002; 359:1102-7.

 

Levadoux A et Tournaire M. « DES Trois générations : réalités – perspectives ».Réseau des éditeurs, diffusion

Vigot Paris 2010, 216 p.

 

O’Reilly E, Mirzaei F et coll. “ Diethylstilbestrol exposure in utero and depression in women” Am J Epidemiol

2010; 171(8): 876-82.

 

Palmer JR, Hatch EE et coll. “Risk of breast cancer in women exposed to diethylstilbestrol in utero : preliminary

results (United States) ”. Cancer Causes Control 2002; 13:753-8.

 

Palmer JR, Wise LA et coll. “Hypospadias in sons of women exposed to diethylstilbestrol in uteroEpidemiology

2005; 16(4):583-6.

 

Palmer JR, Wise LA, Hatch EE et coll. “Prenatal diethylstilbestrol exposure and risk of breast cancer”. Cancer

Epidemiol Biomarkers 2006; 15(8):1509-14.

 

Pons JC, Papiernik E et coll. “Hypospadias in sons of women exposed to diethylstilbestrol in uteroPrenatal

Diagn. 2005; 25(5):418-9.

 

Troisi R, Hatch EE et coll. “Cancer risk in women prenatally exposed to diethylstilbestrol” Int J Cancer 2007;

121(2): 356-60.

 

Van Dijck JA et coll. “Vaginal and cervical cancer due to diethylstilbestrol (DES); end epidemic” Ned Tudschr

Geneeskd 2009; 153(37): A366.

 

Verdoux H, Clavel-Chapelon F et coll. “ Serious psychiatric outcome of subjects prenatally exposed to

diethylstilboestrol in the E3N cohort study” Psychol Med 2007; 37(9): 1315-22.

 

Verloop J, van Leeuwen FE et coll. “Cancer risk in DES daughters” Cancer Causes Control 2010; 21(7): 999-

1007.