DES use as a postcoital contraceptive agent, 1970

Endometrial Carbonic Anhydrase After Diethylstilbestrol as a Postcoital Antifertility Agent

1970 Study Abstract

Others have shown that the oral administration of diethylstilbestrol 25 mg daily for 5 days is an effective postcoital antifertility method.

This dose of the estrogen was started in 4 volunteers on the day basal temperature rose.

Endometrial carbonic anhydrase, 5 days after the temperature rise, was lowered to an average of 9.8 enzyme units (EU)/g as compared to the average control value of 21.2 EU/g.

This decreased carbonic anhydrase activity may represent a barrier to implantation, although other antifertility mechanisms may also be activated by diethylstilbestrol.


  • Endometrial Carbonic Anhydrase After Diethylstilbestrol as a Postcoital Antifertility Agent, Obstetrics & Gynecology, greenjournal, September 1970.
  • Featured image credit Nicholas Gercken.

DES as genotoxic agent leading to breast cancer

Can estrogenic radicals, generated by lactoperoxidase, be involved in the molecular mechanism of breast carcinogenesis?

2000 Study Abstract

Mutations of regulatory genes, which perturb the mechanism of cell replication resulting in abnormal cell proliferation, are the main cause of cancer.

Many endogenous and exogenous chemicals (including estrogenic hormones) are known to represent a major carcinogenic risk for humans. 2-OH- and 4-OH-derivatives of estrogenic molecules have been shown to form stable adducts with purine DNA bases and act as ‘depurinating’ agents, thus altering gene transcription.

Lactoperoxidase (LPO), which is produced by mammary glands, is likely to be involved in breast carcinogenesis, because of its ability to interact with estrogenic hormones and oxidise them through two one-electron reaction steps.

We investigated the reactivity of LPO towards five molecules:

  • 17-beta-estradiol (a natural hormone),
  • diethylstilbestrol (a synthetic drug, supplied to pregnant women for preventing spontaneous abortion),
  • exestrol (a synthetic antigonadotropic estrogen),
  • 2-OH-
  • and 4-OH-estradiol (catabolic products of estradiol).

Enzymatically generated radical derivatives of such molecules were stabilized by spin-trapping or by chelation of a diamagnetic metal ion and characterized with EPR spectroscopy. A kinetic study of the oxidation process was carried out using EPR and UV-visible spectroscopy.


  • Can estrogenic radicals, generated by lactoperoxidase, be involved in the molecular mechanism of breast carcinogenesis?, Redox report : communications in free radical research, NCBI PubMed PMID: 10994878, 2000.
  • Image credit Grace Madeline.

Post-coital DES in large doses

DES use as a postcoital contraceptive agent is discussed

1972 Study Abstract

To study the contraceptive effective in human beings, large doses of estrogen were administered to 2000 women between 14 and 52 years of age.

In 1418 cases (71%) ethinyloestradiol (EO) was used, in 524 cases (26%) diethylstilbestrol (DS), and in 58 cases (3%) the estrogen administered was not recorded.

In 47.5% the unprotected coitus occurred between 12 and 16 days before the next expected menstruation, in 60.9% it occurred between 10 and 17 days, and in 9.6% (193 cases) the day of the cycle was not mentioned.

There were 14 pregnancies among the 2000 women. In only 3 cases did the pregnancy occur after 3 mg doses of EO or 30 mg DS started within 36 hours. No pregnancies occurred after 5 mg EO or 50 mg DS. In 3 cases the pregnancy could have been the result of a later unprotected coitus. In another 3 cases medication was started after more than 48 hours.

In cases of vomiting occurring within 1 hour after ingestion of a tablet, another tablet was given 30 minutes after an anti-emetic. If all tablets were vomited estradiol benzoate, 30 mg per day for 5 days, was injected. Other side effects were tender breasts, menorrhagia, headache, dizziness, abdominal pain, and amenorrhea. Changes in their cycle were reported by 662 women. Most stabalized after 1 cycle. Side effects prohibit this method for routine contraception but it could be valuable in special cases.

There is as yet no statistical proof of its degree of effectiveness. The method of action of these drugs is not certainly known.



Carcinogenicity of estrogens in human breast epithelial cells

image of breast epithelial cells

DES induces in HBEC phenotypic changes indicative of cell transformation, associated with significant genomic alterations

2001 Study Abstract

Epidemiological and clinical evidences indicate that breast cancer risk is associated with prolonged ovarian function that results in elevated circulating levels of steroid hormones. Principal among these is estrogen, which is associated with two important risk factors, early onset of menarche and late menopause.

However, up to now there is no direct experimental evidence that estrogens are responsible of the initiation of human breast cancer. We postulate that if estrogens are causative agents of this disease, they should elicit in human breast epithelial cells (HBEC) genomic alterations similar to those exhibited by human breast cancers, such as DNA amplification and loss of genetic material representing tumor suppressor genes. These effects could result from binding of the hormone to its nuclear receptors (ER) or from its metabolic activation to reactive metabolites.

This hypothesis was tested by treating with the natural estrogen 17beta-estradiol (E2) and the synthetic steroid diethylstilbestrol (DES) MCF-10F cells, a HBEC line that is negative for ER. Cells treated with the chemical carcinogen benzo (a) pyrene (BP) served as a positive control of cell transformation.

BP-, E2-, and DES-treated MCF-10F cells showed increases in survival efficiency and colony efficiency in agar methocel, and loss of ductulogenic capacity in collagen gel. The largest colonies were formed by BP-treated cells, becoming progressively smaller in DES- and E2-treated cells. The loss of ductulogenic capacity was maximal in BP-, and less prominent in E2- and DES-treated cells. Genomic analysis revealed that E2- and DES-treated cells exhibited loss of heterozygosity in chromosomes 3 and 11, at 3p21, 3p21-21.2, 3p21.1-14.2, and 3p14.2 14.1, and at 11q23.3 and 11q23.1-25 regions, respectively. It is noteworthy that these loci are also affected in breast lesions, such as ductal hyperplasia, carcinoma in situ, and invasive carcinoma.

Our data are the first ones to demonstrate that estrogens induce in HBEC phenotypic changes indicative of cell transformation and that those changes are associated with significant genomic alterations that might unravel new pathways in the initiation of breast cancer.


  • Carcinogenicity of estrogens in human breast epithelial cells, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, NCBI PubMed PMID: 11297193, 2001 Jan.
  • Image credit scitechdaily.

The “morning-after pill”

The use of diethylstilbestrol (DES) as a postcoital contraceptive agent is discussed

1971 Study Abstract

A course of post-coital estrogens, in adequate dosage, is a highly effective and safe (though misnamed) form of post-coital contraception that deserves to be more widely known and prescribed. Both unwanted pregnancies and the demand for abortion could be reduced by its widespread use in emergency situations.

Several natural and synthetic estrogens have been used in various dosages; a popular regimen is 5 milligrams of stilbestrol, 5 times per day for 5 days, preferably accompanied by an anti-emetic, since nausea and occasional vomiting may occur.

Some authorities advise starting the course of estrogens within 48 hours of unprotected intercourse and others set a reliable outside limit of 72 hours, turning a Friday night indiscretion into a Monday morning routine appointment rather than a weekend emergency.

For a series of 30 cases started on the above dosage within 72 hours of coitus without contraception or with condom failure, I am able to report no pregnancies. These patients proved particularly responsive to counselling, almost all keeping subsequent appointments for a more satisfactory method of birth control.

Similar success was reported verbally at the recent American College Health Association conference1 by a gynecologist from Yale.

An interim report from the University of Utrecht indicated no failures in 72 women using post-coital estrogens, and a comprehensive review of the literature on the subject, with an analysis of 1000 cases, is to be presented by the same author at the forthcoming Fertility-Sterility Conference in Tokyo in October.

Professor Haspels’ excellent paper should do much to clear up the confusion that exists in many minds between this highly reliable method of post-coital contraception and the virtually useless attempts that are sometimes made to terminate a pregnancy by administering estrogens after a missed menstrual period.

This subject is, of course, unrelated to the use of prostaglandins, which is an entirely different story.


  • The “morning-after pill”, Canadian Medical Association journal, NCBI PubMed PMC1931140, 1971 Aug 7.

DES Research Heats Up Again After Breast Cancer Finding

Journal of the National Cancer Institute, August 1999

“Based on continued cohort studies, we are now fairly sure that DES women face a 20% to 30% excess risk for breast cancer,”

Robert Hoover, M.D., director of the Epidemiology and Biostatistics Program at the National Cancer Institute

“DES could serve the study of other potential estrogenic cancer-causing compounds and environmental estrogens — none are as potent as DES and it would make an excellent model,”

Retha Newbold, head of the Developmental Endocrinology Section at the National Institute of Environmental Health Sciences, Research Triangle Park, N.C.

Another recommendation from the group was that researchers start to examine grandchildren of DES-exposed women, as they too may have a potential for DES cancers.

Read the full paper DES Research Heats Up Again After Breast Cancer Finding on Oxford University Press, 18 August 1999.


Maternal factors and breast cancer risk among young women

Intrauterine DES exposure and subsequent risk of breast cancer

1998 Study Abstract

The results from previous studies have provided evidence to support the hypothesised association between intrauterine oestrogen exposure and subsequent risk of breast cancer. Information has not been available to study this relationship for several perinatal factors thought to be related to pregnancy oestrogen levels.

Data collected from the mothers of women in two population-based case-control studies of breast cancer in women under the age of 45 years (510 case mothers, 436 control mothers) who were diagnosed between 1983 and 1992 in three western Washington counties were used to investigate further the relationship between intrauterine oestrogen exposure and risk of breast cancer.

A pregnancy weight gain of 25-34 pounds was associated with breast cancer risk (odds ratio [OR] = 1.5; 95% confidence interval [CI] 1.1, 2.0); however, women whose mothers gained 35 pounds or more were not at increased risk. Use of antiemetic medication in women with any nausea and vomiting (OR = 2.9; 95% CI 1.1, 8.1) and use of diethylstilboestrol (DES) (OR = 2.3; 95% CI 0.8, 6.4) appeared to be positively associated with breast cancer risk.

The results from this study provide limited support for the hypothesis that in utero oestrogen exposure may be related to subsequent breast cancer risk among young women.


  • Maternal factors and breast cancer risk among young women, Paediatric and perinatal epidemiology, NCBI PubMed PMID: 9805713, 1998 Oct.
  • Image credit Asdrubal luna.

Postcoital contraception : present and future options

DES still used for emergency contraception in 1995


This article reviews information on currently available postcoital contraceptives, and discusses recent advances in postcoital contraception, mostly notably RU 486.

Postcoital contraceptives, or “morning after pills,” are currently available in the form of high dose estrogens, oral contraceptives, danazol and intrauterine devices. These methods are plagued by high incidences of side effects and less than optimal success rates.

Currently, their primary use in the adolescent age group is for victims of sexual assault, but they may also be used as back-up for consensual unprotected intercourse. RU 486, best known as a first trimester abortifacient, has a number of potential uses, including that of a postcoital contraceptive. Two recently published studies from the UK showed RU 486 to have a very low pregnancy rate and fewer side effects when compared with current methods. RU 486 may someday replace high doses of oral contraceptives as the method of choice for postcoital contraception.

Postcoital contraceptives are available for adolescent use in the US. They include combination oral contraceptives (OCs), high dose estrogens, danazol, and IUDs. Mifepristone (RU-486) is currently not available in the US but is used in France, the UK, and Sweden. Postcoital contraception is especially important for adolescents who have a very high pregnancy rate due to poor contraceptive use. Administration of 2-5 mg ethinyl estradiol (EE) for 5 days beginning within 72 hours of unprotected intercourse yields pregnancy rates ranging from 0-0.92%. EE-related side effects include nausea, vomiting, sore breasts, and irregular menstrual bleeding. DES should not be used, since it is associated with reproductive tract anomalies and vaginal cancers in exposed offspring. Conjugated estrogens have not been used in adolescents for postcoital contraception. The Yuzpe regimen consists of 2 tablets of a combined OC with 200 mg EE and 2 mg dl-norgestrel administered within 72 hours of unprotected intercourse followed by the same dose 12 hours later. Common side effects are nausea and vomiting. Its pregnancy rate is 1.8%. Levonorgestrel-containing OCs can also be used. Administration of 800-1200 mg danazol up to 120 hours after unprotected intercourse protects against pregnancy in about 98% of cases. Copper IUDs have a high efficacy rate when used as postcoital contraception (99.9%), but public opinion, medicolegal considerations, financial costs, and potential for infection impede IUD as a postcoital contraceptive in the US. RU-486 is best known as an abortifacient. It is also a potential postcoital contraceptive. Two UK studies find that RU-486 used as a postcoital contraceptive has a very low pregnancy rate and fewer side effects than the Yuzpe regimen and danazol. It is much more costly than currently used postcoital contraceptives (600 mg of RU-486 cost US$ 68, while Ovral costs US$ 0.48-2.24). Nevertheless, RU-486 may replace the higher doses of OCs as a postcoital contraceptive method.


  • Postcoital contraception: present and future options, The Journal of adolescent health : official publication of the Society for Adolescent Medicine, NCBI PubMed PMID: 7742340, 1995 Jan.

DES and breast cancer risk

Experimental study on relationship between exogenous estrogen and breast cancer risk

1997 Study Abstract

To investigate the relationship between exogenous estrogen and breast cancer risk.

Female rats were randomly divided into three groups, namely diethylstilbestrol (DES), norethindrone compositae (CoNET) and control group. The histological structure and ultrastructural changes of mammae were observed. The levels of sexual hormones in serum were determined and the AgNOR counts, DNA contents and steroid receptor contents in mammary epithelium were also detected.

In DES group, the level of progesterone (10.38 ng/ml) was obviously lower than that in the control group (13.37 ng/ml); the incidence of hyperplasia of mammary gland (73.33%) was significantly higher than that in the control group (7.69%); and the degree of hyperplasia was obviously more serious than that in the control group. Moreover, there were 13.33% of rats with atypical hyperplasia in DES group. The DNA contents, AgNOR counts and estrogen receptor (ER) positive rate were markedly higher in DES group (95.60, 2.43 and 71.71% respectively) than in the control group (83.07, 1.88 and 40% respectively). However, in CoNET group, there were no obvious influences on ER, AgNOR and DNA in mammary epithelium.

Exogenous estrogen (DES) could affect the levels of sexual hormones in serum, accelerate the DNA duplication, increase the AgNOR counts and ER contents, and induce atypical hyperplasia and ultrastructural changes of mammary gland, hence becoming a latent risk factor of breast cancer. However, the results failed to suggest that the contraceptive, CoNET, could increase the risk of breast cancer.


  • Experimental study on relationship between exogenous estrogen and breast cancer risk, Chinese medical journal, NCBI PubMed PMID: 9594309, 1997 May.