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

What is DES?

Diethylstilbestrol: introduction

Diethylstilbestrol is known under many different names, but the most common abbreviation is "DES", which is why we often use it on the website.

Diethylstilbestrol is the best known synthetic estrogen. It was synthesized in 1938 by E.C Dodds. Find out more about the synthesis of diethylstilbestrol at DES Timeline.

 

Ball-and-stick model of the diethylstilbestrol molecule, also known as stilbestrol, a nonsteroidal estrogen which is mostly no longer used. Join DES is it french organization!
Ball-and-stick model of the diethylstilbestrol molecule
Formula: C18H2002
Other names: DES; Stilboestrol; Stilbestrol

 

Diethylstilbestrol appears as an odorless white powder made up of colorless crystals1.

Diethylstilbestrol has a melting point of 169 -172 ° C (336 to 342 °F). It is practically insoluble in water and chloroform, soluble in ethanol, methanol, benzene, light petroleum ether, chloroethane, acetone, and potassium hydroxide, and very soluble in oils and fats.

 

Example of white powder that Diethylstilbestrol looks like. Join DES is it french organization!

 

If diethylstilbestrol is the most known synthetic hormone, it is not the first to have been synthesized and to have been given to pregnant women.

Paroxypropione was synthesized in 1902, but its antigonadotropic properties were only discovered in 1951.

It was marketed in France by Laroche-Navarron laboratories under the brand name Frénantol® from 1953, and, if it was mainly used to treat hyperthyroidism-related problems, it was also prescribed to prevent late spontaneous abortions associated with an hypersecretion of luteinizing hormone2. However, it did not have a very strong estrogenic activity and was not marketed for long, unlike diethylstilbestrol.

We do not know if it may have been consequences, but what we can say is that paroxypropione is a chemical precursor in the synthesis of diethylstilbestrol and dienestrol.

 

Frénantol® Medication 5mgr (paroxypropione) by Laroche-Navarron laboratories
Frénantol® Medication 5mgr
Laroche-Navarron laboratories

Exploitation of diethylstilbestrol

Since its inventor, Dr. Dodd’s, has not filed a patent, diethylstilbestrol has been produced by different laboratories and marketed in France and other countries under different various brand names (Stilbœstrol-Borne®, Distilbene® and Furostilbœstrol® in France) and in different forms: tablets, injections, creams, vaginal suppositories...

Other synthetic estrogens similar to diethylstilbestrol were marketed at the same time, notably dienestrol and hexestrol.

 

Examples of medication boxes

Distilbène® (diethylstilbestrol) medication 1mg tablets by M. Borne french Laboratories
Distilbène® (diethylstilbestrol) medication 1mg tablets by M. Borne french Laboratories

 

Distilbène® medication 5mg tablets by M. Borne french Laboratories
Distilbène® medication 5mg tablets by M. Borne french Laboratories

 

Box of Cycladiène® 5mgr, Tube of 20 dienœstrol tablets by Bruneau & C Laboratories, front Box of Cycladiène® 5mgr, Tube of 20 dienœstrol tablets by Bruneau & C Laboratories, back
Box of Cycladiène® 5mgr
Tube of 20 dienœstrol tablets
By Bruneau & C Laboratories

 

Examples of drug advertising campaigns that were sent to doctors

Pharmaceutical Blotter Advertising Dienoestrol Fraysse, Published by Fraysse & C Laboratories, Illustration by Albert DUBOUT (front)
"Stormy Weather of Menopause. Yes, darling, I know... but, please, take your pills!"

 

Pharmaceutical Blotter Advertising Dienoestrol Fraysse, Published by Fraysse & C Laboratories, Illustration by Albert DUBOUT (back)
Pharmaceutical Blotter Advertising Dienoestrol Fraysse
Published by Fraysse & C Laboratories
Illustration by Albert DUBOUT

DiEthylStilbestrol (DES): a synthetic estrogen

The body makes three major forms of estrogens:

  1. estrone or œstrone (E1)

  2. estradiol or œstradiol (E2)

  3. estriol or œstriol (E3)

They are present in both men and women, just in differing amounts.

 

Structure of Estrone
Structure of Estrone
Structure of Estradiol
Structure of Estradiol
Structure of Estriol
Structure of Estriol

 

These natural estrogens contain, like all steroids, a sterol nucleus.

Although they can mimic their effects by binding to hormone receptors, synthetic hormones have nothing to do with the natural hormones produced by the human body. These substances are foreign can interfere with the hormone signaling in different ways and cause many adverse effects.

 

Diethylstilbestrol do not have a steroidal chemical structure: it is a non-steroidal estrogen.

 

Sterol chemical structure
Sterol chemical structure
Structure du diethylstilestrol, un oestrogène non-stéroïdien
Structure of Diethylstilbestrol

 

Non-steroidal estrogens are teratogenic, from the Greek teras, teratos, "monster" and genos, "origin", literally meaning, "monster making".

A so-called “teratogenic” substance is harmful because it can disrupt fetal development and cause congenital malformations in children exposed during the fetal period.

 

human fetus and dna medical concept graphic and scientific background, Non-steroidal estrogens, such as DES, are teratogenic

List of synthetic non-steroidal estrogens that have been used that are chemically similar to diethylstilbestrol3

Non Steroidal Estrogens

Benzestrol Fonatol Restrol
Chlorotrianisene Gynben Stil-Rol
Comestrol Gyneben Stibale
Cyren A. Hexestrol Stilbestrol
Cyren B. Hexoestrol Stilbestronate
Delvinal Hi-Bestrol Stilbetin
DES Menocrin Stilbinol
DesPlex Meprane Stilboestroform
Dibestil Mestilbol Stilboestrol
Diestryl Methallenestril Stilboestrol DP
Dienestrol Microest Stilestrate
Dienoestrol Mikarol Stilpalmitate
Diethylstilbestrol Dipalmitate Mikarol forti Stilphostrol
Diethylstilbestrol Diphosphate Milestrol Stilronate
Diethylstilbestrol Dipropionate Monomestrol Stilrone
Diethylstilbenediol Neo-Oestranol I Stils
Digestil Neo-Oestranol II Synestrin
Domestrol Nulabort Synestrol
Estilben Oestrogenine Synthoestrin
Estrobene Oestromenin Tace
Estrobene DP Palestrol D. Vallestril
Estrosyn Palestrol Willestrol

Non Steroidal Estrogen-Androgen Combinations

Amperone Metystil Tylandril
Di-Erone Teserene Tylostrerone
Estran    

Non Steroidal Estrogen-Progesterone Combinations

  • Progravidium

Vaginal cream – suppositories with Non Steroidal Estrogen

  • AVC Cream with Dienestrol
  • Dienestrol Cream

Diethylstilbestrol Indications

Betwen 1948 and1980

In human medicine

Diethylstilbestrol (DES) has been prescribed for a wide range of indications:

  • To prevent miscarriages and premature births, until 1977 (in France);
  • Gestational diabetes4;
  • Inhibition of lactation (artificial suppression of the milk supply after delivery) - Distilbene® (diethylstilbestrol) or Cycladiene® (hexadiene), possibly combined with androgens, until 1980 (in France)5;
  • Hypogalactia (low milk supply during breast-feeding);
  • To treat estrogen deficiency;
  • In case of amenorrhea (by the age of 16);
  • To avoid painful periods and dysmenorrhea (menstrual cramps);
  • To treat gynecological menorrhagia;
  • Vaginitis (inflammation of the vagina);
  • Breast hypoplasia (underdeveloped breasts);
  • Breast ptosis (sagging breasts);
  • Breast cancer;
  • To treat pre-menopausal and menopausal symptoms, such as migraines, insomnia, hot flashes, venous insufficiency, eczema, osteoporosis, rheumatism or vulvar pruritus (itchy vulva);
  • Pubertal disorders, such as acne7;
  • Genital infantilism (underdevelopment of the genitals);
  • Psychoses;

Since DES was also sold on the black market9, anecdotally, transgender people have consumed it without any medical control8;

It has also reportedly been prescribed as an anabolic agent among athletes9;

Abroad, it has been prescribed to pre-teem girls who were at risk of becoming "too tall" to inhibit growth10.

Vidal Dictionary Monograph, 1961 (37th edition) - Distilbène® (diethylstilbestrol).
Vidal Dictionary Monograph, 1961 (37th edition) - Distilbène® (diethylstilbestrol).
(Reference: Le diéthylstilbestrol : Mise au point des connaissances en 2002)

In veterinary medicine

In early 194711, synthetic hormones, such as diethylstilbestrol (DES), were administered to cattle, either as feed additives or as implants. The objective was clear: to fatten them up. Indeed, the anabolic properties of diethylstilbestrol allowed to increase their growth by promoting water retention in the muscles.

More meat, more profits.

Since the scandal only broke out in the early 1980s, many people consumed it without their knowledge.

The use of synthetic estrogens was a fraud because it can be assumed that the consumer who bought the meat would not have bought it if he had known it contained estrogens, especially as no scientific research had been carried out to assess the impact on consumer health.

Sadly, the adverse health effects of eating hormone-treated meat were later widely known.

Implantation instrument for chemical caponisation of poultry. For use with hexoestrol implantation tablets 15mg strenght.
Implantation instrument for chemical caponisation of poultry.
For use with hexoestrol implantation tablets 15mg strenght.

Nowadays

Abroad, in countries such as China or Thailand, it seems to be easy to obtain diethylstilbestrol (DES). For example, online stores offer it to sportsmen and women as an anabolic agent12.

In the United States and other countries, DES is used to treat urinary incontinence in dogs and cats, and benign prostatic hyperplasia in dogs13.

In France and abroad, DES is still used to treat resistant prostate cancers in men. In France, it is now its only indication; in addition to being poorly tolerated, it does not bring any improvement in the treatment of prostate cancer14.

Mechanism of action of diethylstilbestrol

Diethylstilbestrol has estrogenic activity similar to estrone but more active than estrone: 0.3 mg diethylstilbestrol is equivalent to the effect of 1 mg estrone. This drug surpasses both estrone and hexestrol.

Diethylstilbestrol was prescribed precisely for this potent estrogenic activity.

Therefore, among symptoms of DES exposure are those of hyperestrogenism: early puberty, premenstrual syndrome (PMS), endometriosis, risk of developing benign or malignant estrogen-dependent tumors...

High estrogen levels are clearly linked to an increased risk of obesity and cancer. Diethylstilbestrol is fat-soluble and thus can accumulate in fatty tissues; therefore, DES has an obesogenic action15.

Diethylstilbestrol is one of a number of substances that cross the placental barrier. As a result, Distilbene® (a french medicine containing diethylstilbestrol) ingested by pregnant women not only poisoned them, but also directly poisoned the child they were carrying, and just as much poisoned the future children of that child because their germ cells were also exposed to the drug.

This is what D.E.S is it sadly call "the Matryoshka effect of DES".

Thus, it is indeed three generations that have been directly exposed to diethylstilbestrol. That’s why congenital urogenital anomalies are found in the three generations.

The gonads are a vulnerable target for endocrine disruptors such as diethylstilbestrol. This is why we find in people exposed in utero: disorders of sex differentiation (DSD, ambiguous genitalia, pseudohermaphroditism, abnormal secretion of testosterone, hypersecretion of androgens...).

Photo représentant un couple obèse, illustrant l'action obésogène d

Diethylstilbestrol: a Model of Endocrine Disruptor

Diethylstilbestrol (DES), like other stilbenes, is carcinogenic and genotoxic in both animals and humans.

It is an endocrine disruptor. Endocrine disruptors are believed to act by altering the mechanisms of hormone action, and thus the normal functioning of the human body.

Diethylstilbestrol creates iatrogenic (from the Ancient Greek ἰατρός, "physician", and γένεσις, "origin", literally meaning "caused by the physician") side effects in the descendants of women who took DES.

It is now known that fetal exposure to endocrine disruptors may affect neurodevelopment and increase risk of developing psychiatric disorders.

D.E.S is it demands that diethylstilbestrol be definitively banned, for any use whatsoever, human or animal, in France and worldwide, in order to ensure the preservation of human reproduction: the very foundation of life.

 

The international pictogram for chemicals that are sensitising, mutagenic, carcinogenic or toxic to reproduction. Diethylstilbestrol: a Model of Endocrine Disruptor

References

Le diethylstilboestrol – Recherche dans les péparations injectables et dans les carcasses de veau – Thèse de Jean-Michel Baronnie ; Le stilboestrol  Actualités Médicales n°4

2 Laboratoires Laroche-Navarron - Fiche n°6 Frénantol - Les avortements spontanés à répétition, Avril 1953.

Diethylstilbestrol – New perspectives, Davd A. Edelman

Questions and Answers about DES Exposure Before Birth – National Cancer Institute (U.S.)

Ostétrique  DCEM & Sages Femmes, de P. Lopes

Fabrice Rivollier. Exposition prénatale aux perturbateurs endocriniens et risque sur le neuro développement : étude de fratries exposées au diéthylstilbestrol. Médecine humaine et pathologie. 2015.

Perrine Planchon. Les perturbateurs endocriniens dans les produits de santé. Sciences pharmaceutiques. 2014. ffdumas-01081489f

8 L'Obs, par Nathalie Bensahel. Marie-Pierre : "J'ai longtemps été blâmée, humiliée". 2015.

9 Dane Morin-Delacroix. L'affaire Distilbène ou Mutilations sur ordonnances. Éditions Edilivre.

10 DES Centrum  Groeiremming bij DES ?

11 Nora Cesbron - Les SARMs (Selective Androgen Receptor Modulators) : une nouvelle famille d'agents anabolisants. Etude des effets zootechniques associés et développement de stratégies analytiques visant la mise en évidence de leur utilisation chez le jeune bovin. 07 juin 2017.

12 Wuhan Demeikai Biotechnology Co., Ltd; Hongkong XinRunde Chemical Co., Ltd.

13 Dr. Barbara Forney, veterinary practitioner in Chester County, Pennsylvania. Diethylstilbestrol (DES) for dogs; Stilbestrol Tablets 0.5mg drugs.com; PetCoach, Diethylstilbestrol.

14 Haute Autorité de Santé. DISTILBENE (diéthylstilbestrol), hormones AVIS SUR LES MÉDICAMENTS. Mis en ligne le 13 mai 2016.

15 Newbold RR1, Padilla-Banks E, Jefferson WN Environmental estrogens and obesity; Darbre, P.D. Curr Obes Rep (2017) 6: 18. Endocrine Disruptors and Obesity