Chargement de la page
Logo of D.E.S is it, DES Action group in France (Diethylstilbestrol)

Back to news

Several cases of clear cell adenocarcinoma (CCAC) reported in DES granddaughters (diethylstilbestrol)

Several cases of Clear Cell Adenocarcinoma (CCA) in DES Granddaughters (diethylstilbestrol)

Diethylstilbestrol (DES) has been marketed in many countries by several pharmaceutical companies under different brand names. It has been widely prescribed to pregnant women to prevent miscarriages.

Thanks to a study by W.J. Dieckmann, it was known, as early as 1953 that this treatment was ineffective in pregnant women for all its indications. Despite, the marketing and prescriptions of DES continued.

In 19701 and 19712, A.L Herbst published two studies that revealed an increased incidence of a very rare type of cancer in DES Daughters (exposed in utero to the molecule): clear cell adenocarcinoma (CCA) of the vagina or cervix.

Following this discovery, the FDA (Food and Drug Administration) issued an alert in 1971 about the use of DES in pregnant women and raised the alarm. Nevertheless, DES continued to be prescribed until 1977 in France, 1980 in Spain, 1981 in Italy and 1983 in Hungary...

The exact number of women who took DES during their pregnancy(s) is not known, but it is estimated that there were between 5 and 10 million women in the world, including about 200,000 women in France (under the brand names: Distilbene®, Stilbestrol-Borne® or Furostilboestrol®).
Since its ban, diethylstilbestrol – a known endocrine disruptor – has been found to cause many other health problems in children exposed in utero, as well as in their children: DES third generation.

In order to find out how many victims there are, our association D.E.S is it has also launched a large national census of DES victims, which can be found on the following page: https://www.recensement-victimes-distilbene-stilbestrol.des-is-it.org.

 

Several cases of Clear Cell Adenocarcinoma (CCA) in DES Granddaughters (diethylstilbestrol)

Since 1971, further studies have confirmed and detailed this increased risk for DES Daughters to develop Clear-cell Adenocarcinoma of the vagina and cervix.

In 20033, a first case of ovarian carcinoma was reported in a 15-year-old third-generation adolescent girl (whose grandmother took DES while pregnant) which, although considered anecdotal, already raised the possibility of a transgenerational effect of DES, particularly since this type of tumor is rare in adolescent girls.

In 20184, the American association DES Info reported two cases of Clear-cell Adenocarcinoma of the vagina in DES granddaughters. These were the first reported cases of CCA. The NIH (National Institutes of Health), the NIEHS (National Institute of Environmental Health Sciences), and scientists were notified.

In 20205, a new study – reported by the French press, including Midi Libre and La Dépêche – reported a case of Clear-cell Adenocarcinoma of the cervix in an 8 year old girl whose grandmother had been treated with DES.

The researchers of this study were apparently unaware of the cases reported by the association DES Info, since they presented this case as the first case of CCA in a DES granddaughter, which is therefore, unfortunately, not the reality.

We feel we can also assume that other cases exist since the general public was not informed of the case of this girl – now 18 years old – until 10 years later.

We are glad that the various treatments she underwent keeps her in good health, without any recurrence or side effects.

 

What is Clear cell adenocarcinoma (CCA)?

Clear-cell adenocarcinoma is a rare tumor, usually located in the female internal reproductive organs.

According to the International Federation of Gynecology and Obstetrics (FIGO), a tumor that occupies both the vagina and the cervix is considered to originate in the vagina if the external os of the cervix is not involved.

Figure 1 at the top of the article depicts the first two stages of cervical ACC:

  • Stage 1: Adenocarcinoma is confined to the cervix; the lesion may have a cauliflower-like (exophytic) appearance; while remaining on the cervix, the cancer may spread.
  • Stage 2: The adenocarcinoma extends into the upper part of the vagina and into the parametrium (tissue that surrounds the uterus and cervix), but does not extend to the pelvic wall.
  • Stage 3: Adenocarcinoma extends to the anterior (front) vaginal wall, extends to the lower third of the vagina and may reach the pelvic walls; the lesion invades the pelvic wall, causing kidney damage.
  • Stage 4: The lining of the bladder or rectum is affected; the cancer may spread to other parts of the body (metastases).
Several cases of Clear Cell Adenocarcinoma (CCA) in DES Granddaughters (diethylstilbestrol)

Figure 2 – Colposcopy of the the cervix shows CCAC
Copyright © DES Info

 

Recognizing Signs and Symptoms of CCA

Signs & symptoms of vaginal CCA

  • Abnormal vaginal bleeding (metrorrhagia), which can occur after sexual intercourse, after menopause, or between menstrual periods;
  • Smelly or bloody vaginal discharge;
  • Painful sexual intercourse (dyspareunia);
  • A mass in the vagina that can be felt;
  • Pain in the pelvis, back, legs and/or perineum;
  • Burning sensation, frequent and urgent urination (urinary frequency) and blood in the urine (hematuria):
  • Changes in intestinal transit, presence of blood in the stool (rectal bleeding), constipation and pain during defecation;
  • Groin or legs swelling.

Signs & symptoms of cervical cancer

  • Painless abnormal vaginal bleeding (induced metrorrhagia), after sexual intercourse, after menopause, or between periods;
  • Abnormal discharge (leucorrhoea, hydrorrhoea);
  • Unusually prolonged or heavy menstrual periods;
  • Painful intercourse (deep dyspareunia);
  • Pelvic pain (algies);
  • Urinary disorders: burning sensation, frequent and urgent urination (pollakiuria) and presence of blood in the urine (hematuria), difficulty in urinating: leakage of urine or stool through the vagina;
  • Rectal disorders: intestinal or abdominal contraction ending in a pressing and urgent need to defecate, false needs (épreinte), painful contraction often accompanied by burning sensation in the anus, presence of blood in the stool;
  • Abdominal pain (ascites), lumbar pain (hydronephrosis), which can go down along one or both legs;
  • Bloody sputum;
  • Altered health status (loss of appetite and weight loss, shortness of breath, fatigue...).

 

Since the cases of CCA, especially at such a young age, are rarely reported outside of exposure to diethylstilbestrol, a transgenerational effect can clearly be envisaged for the CCA found in DES granddaughters.

Therefore, we encourage victims to report their history of exposure to this non-steroidal estrogen to their physician(s), and we invite physicians who encounter CCA in women to be concerned about possible DES exposure, direct or indirect, and to report the cases.

 

References

1 Herbst AL, Scully RE. Adenocarcinoma of the vagina in adolescence. A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas). Cancer. 1970 Apr;25(4):745-57. doi: 10.1002/1097-0142(197004)25:4<745::aid-cncr2820250402>3.0.co;2-2. PMID: 5443099.

2 Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878-81. doi: 10.1056/NEJM197104222841604. PMID: 5549830.

3 Blatt J, Van Le L, Weiner T, Sailer S. Ovarian carcinoma in an adolescent with transgenerational exposure to diethylstilbestrol. J Pediatr Hematol Oncol. 2003 Aug;25(8):635-6. doi: 10.1097/00043426-200308000-00009. PMID: 12902917. https://pubmed.ncbi.nlm.nih.gov/12902917/

4 DES Info reported two cases of Clear Cell Adenocarcinoma of the Vagina in DES Granddaughters in 2018.

5 Laura Gaspari, Françoise Paris, Nathalie Cassel-Knipping, Julia Villeret, Arnauld Verschuur, Marie-Odile Soyer-Gobillard, Xavier Carcopino-Tusoli, Samir Hamamah, Nicolas Kalfa, Charles Sultan, Diethylstilbestrol exposure during pregnancy with primary clear cell carcinoma of the cervix in an 8-year-old granddaughter: a multigenerational effect of endocrine disruptors?, Human Reproduction, , deaa267, https://doi.org/10.1093/humrep/deaa267

Dec 13, 2020 | Scientific studies
DES Third Generation DES Granddaughter clear cell adenocarcinoma (CCAC)
0 Like

0 Comment(s) Comments

There aren't any comments yet.

Already registered?

You must be logged in to post a comment.

Sign in
Forgot password?
* Required Fields
New to D.E.S is it? Join for free!
2019-2023 © Copyright - D.E.S is it