Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is rarely used.[4][5] In the past, it was widely used for a variety of indications, including pregnancy support for women with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency in women, treatment of prostate cancer in men and breast cancer in women, and other uses. Today, it is only used in the treatment of prostate cancer and less commonly breast cancer.[6] While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.

Clinical data
Other namesDES; Stilboestrol; Stilbestrol; (E)-11,12-Diethyl-4,13-stilbenediol
AHFS/Drugs.comMicromedex Detailed Consumer Information
  • X
Routes of
By mouth, vaginal, topical, intravenous, intramuscular injection (as an ester)
Drug classNonsteroidal estrogen
ATC code
Pharmacokinetic data
Protein binding>95%[2]
MetabolismHydroxylation, oxidation, glucuronidation[1][2][3]
Elimination half-life24 hours[1]
ExcretionUrine, feces[2][3]
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.000.253
Chemical and physical data
Molar mass268.356 g/mol g·mol−1
3D model (JSmol)

DES is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol.[5] It is a synthetic and nonsteroidal estrogen of the stilbestrol group, and differs from the natural estrogen estradiol in various ways.[5] Compared to estradiol, DES has greatly improved bioavailability when taken by mouth, is more resistant to metabolism, and shows relatively increased effects in certain parts of the body like the liver and uterus.[5] These differences result in DES having an increased risk of blood clots, cardiovascular issues, and certain other adverse effects.[5]

DES was discovered in 1938.[7] From about 1940 to 1971, the medication was given to pregnant women in the incorrect belief that it would reduce the risk of pregnancy complications and losses.[7] In 1971, DES was shown to cause clear-cell carcinoma, a rare vaginal tumor, in girls and women who had been exposed to this medication in utero.[7] The United States Food and Drug Administration subsequently withdrew approval of DES as a treatment for pregnant women.[7] Follow-up studies have indicated that DES also has the potential to cause a variety of significant adverse medical complications during the lifetimes of those exposed.[7][8]

The United States National Cancer Institute recommends[9] women born to mothers who took DES to undergo special medical exams on a regular basis to screen for complications as a result of the medication. Individuals who were exposed to DES during their mothers' pregnancies are commonly referred to as "DES daughters" and "DES sons".[7][10] Since the discovery of the toxic effects of DES, it has largely been discontinued and is now mostly no longer marketed.[7][11]

Medical uses

DES has been used in the past for the following indications:[12]

DES was used at a dosage of 0.2 to 0.5 mg/day in menopausal hormone therapy.[21]

Interest in the use of DES to treat prostate cancer in men continues today.[22][23][24][25][26][27][28] However, some researchers have advocated for the use of bioidentical parenteral estrogens like polyestradiol phosphate in favor of oral synthetic estrogens like DES due to their much lower risk of cardiovascular toxicity.[29][26][28] In addition to prostate cancer, some interest in the use of DES to treat breast cancer in women continues today as well.[30][31] However, similarly to the case of prostate cancer, some researchers have argued for the use bioidentical estrogens like estradiol instead of DES for breast cancer.[30][32]

Estrogen dosages for breast cancer
OralEstradiol10 mg 3x/day
AI-resistant: 2 mg 1–3x/day
Estradiol valerateAI-resistant: 2 mg 1–3x/day
Conjugated estrogens10 mg 3x/day
Ethinylestradiol0.5–1 mg 3x/day
Diethylstilbestrol5 mg 3x/day
Dienestrol5 mg 3x/day
IM or SC injectionEstradiol benzoate5 mg 2–3x/week
Estradiol dipropionate5 mg 2–3x/week
Estradiol valerate30 mg 1x/2 weeks
Polyestradiol phosphate40–80 mg 1x/4 weeks
Estrone5 mg ≥3x/week
Notes: (1) Only in women who are at least 5 years postmenopausal. (2) Dosages are not necessarily equivalent. Sources: See template.
Estrogen dosages for prostate cancer
OralEstradiol1–2 mg 3x/day
Conjugated estrogens1.25–2.5 mg 3x/day
Ethinylestradiol0.15–3 mg/day
Ethinylestradiol sulfonate1–2 mg 1x/week
Diethylstilbestrol1–3 mg/day
Dienestrol5 mg/day
Hexestrol5 mg/day
Fosfestrol100–480 mg 1–3x/day
Chlorotrianisene12–48 mg/day
Quadrosilan900 mg/day
Estramustine phosphate140–1400 mg/day
Transdermal patchEstradiol2–6x 100 μg/day
Scrotal: 1x 100 μg/day
IM or SC injectionEstradiol benzoate1.66 mg 3x/week
Estradiol dipropionate5 mg 1x/week
Estradiol valerate10–40 mg 1x/1–2 weeks
Estradiol undecylate100 mg 1x/4 weeks
Polyestradiol phosphateAlone: 160–320 mg 1x/4 weeks
With oral EE: 40–80 mg 1x/4 weeks
Estrone2–4 mg 2–3x/week
IV injectionFosfestrol300–1200 mg 1–7x/week
Estramustine phosphate240–450 mg/day
Note: Dosages are not necessarily equivalent. Sources: See template.

Side effects

At doses above 1 mg/day by mouth, DES is associated with high rates of side effects including nausea, vomiting, abdominal discomfort, headache, and bloating, with an incidence of 15 to 50%.[33]

In studies of DES as a form of high-dose estrogen therapy for men with prostate cancer, it has been associated with considerable cardiovascular morbidity and mortality.[23] The risk is dose-dependent.[23] A dosage of 5 mg/day DES has been associated with a 36% increase in non-cancer-related (mostly cardiovascular) deaths.[23] In addition, there is an up to 15% incidence of venous thromboembolism.[34] A 3 mg/day dosage of DES has been associated with an incidence of thromboembolism of 9.6 to 17%, with an incidence of cardiovascular complications of 33.3%.[23] A lower dosage of 1 mg/day DES has been associated with a rate of death due to cardiovascular events of 14.8% (relative to 8.3% for orchiectomy alone).[23]

In men treated with it for prostate cancer, DES has been found to produce high rates of gynecomastia (breast development) of 41 to 77%.[35]

The pigmentation of the breast areolae are often very dark and almost black with DES therapy.[36][37][38][39][40][41] The pigmentation that occurs with synthetic estrogens such as DES is much greater than with natural estrogens such as estradiol.[36]

Long-term effects

DES has been linked to a variety of long-term adverse effects, such as increased risk of vaginal clear-cell adenocarcinoma, vaginal adenosis, T-shaped uterus, uterine fibroids, cervical weakness, breast cancer, infertility, hypogonadism, intersex defects, depression, and others, in women who were treated with it during pregnancy and/or in their offspring.[42]

A comprehensive animal study in 1993 found a plethora of adverse effects from DES such as [but not limited to] genotoxicity (due to quinone metabolite), teratogenicity, penile and testicular hypoplasia, cryptorchidism (rats and rhesus monkeys), liver and renal cancer (hamsters), ovarian papillary carcinoma (canines), and malignant uterine mesothelioma (squirrel monkeys). [43] Evidence was also found linking ADHD to F2 generations, demonstrating that there is at least some neurological and transgenerational effects in addition to the carcinogenic. [44] Rodent studies reveal female reproductive tract cancers and abnormalities reaching to the F2 generation, and there is evidence of adverse effects such as irregular menstrual cycles in grandchildren of DES mothers. [45] Additionally, evidence also points to transgenerational effects in F2 sons like hypospadias. [46] At this time however, the extent of DES transgenerational effects in regards to humans is not fully understood.


DES has been assessed in the past in clinical studies at extremely high dosages of as much as 1,500 mg/day.[30][47]



Estrogenic activity

DES is an estrogen; specifically, it is a highly potent full agonist of both of the estrogen receptors (ERs).[48][49] It has approximately 468% and 295% of the affinity of estradiol at the ERα and ERβ, respectively.[50] However, EC50 values of 0.18 nM and 0.06 nM of DES for the ERα and ERβ, respectively, have been reported, suggesting, in spite of its binding affinity for the two receptors, several-fold preference for activation of the ERβ over the ERα.[51]

A dosage of 1 mg/day DES is approximately equivalent to a dosage of 50 µg/day ethinylestradiol in terms of systemic estrogenic potency.[1] Similarly to ethinylestradiol, DES shows a marked and disproportionately strong effect on liver protein synthesis.[5] Whereas its systemic estrogenic potency was about 3.8-fold of that of estropipate (piperazine estrone sulfate), which has similar potency to micronized estradiol, the hepatic estrogenic potency of DES was 28.4-fold that of estropipate (or about 7.5-fold stronger potency for a dosage with equivalent systemic estrogenic effect).[1]

DES has at least three mechanisms of action in the treatment of prostate cancer in men.[52] It suppresses gonadal androgen production and hence circulating androgen levels due to its antigonadotropic effects; it stimulates hepatic sex hormone-binding globulin (SHBG) production, thereby increasing circulating levels of SHBG and decreasing the free fraction of testosterone and dihydrotestosterone (DHT) in the circulation; and it may have direct cytotoxic effects in the testes and prostate gland.[52] DES has also been found to decrease DNA synthesis at high doses.[52]

DES is a long-acting estrogen, with a nuclear retention of around 24 hours.[53][54]

Relative oral potencies of estrogens
Estrone sulfateBioidentical?––0.71.4–1.50.56–1.7
Conjugated estrogensNatural1.––3.21.3––4.5
Equilin sulfateNatural??1.0??
Notes: Values are ratios, with estradiol as standard (i.e., 1.0). Abbreviations: HF = Clinical relief of hot flashes. VE = Increased proliferation of vaginal epithelium. UCa = Decrease in UCa. FSH = Suppression of FSH levels. LH = Suppression of LH levels. HDL-C, SHBG, CBG, and AGT = Increase in the serum levels of these liver proteins. Liver = Ratio of liver estrogenic effects to general/systemic estrogenic effects (specifically hot flashes relief and gonadotropin suppression). Type: Bioidentical = Identical to those found in humans. Natural = Naturally occurring but not identical to those found in humans (e.g., estrogens of other species). Synthetic = Man-made, does not occur naturally in animals or in the environment. Sources: See template.
Oral potencies of estrogens
(mg/14 days)
(mg/14 days)
(mg/14 days)
Estradiol (non-micronized)BioidenticalSteroidal?≥120–300????
Estradiol (micronized)BioidenticalSteroidal?60–804.314–281.0–2.0>8
Estradiol valerateBioidenticalSteroidal6–1060–804.314–281.0–2.0>8
Estradiol benzoateBioidenticalSteroidal?60–1404.5???
Estriol succinateBioidenticalSteroidal?140–150b10.0–10.7b28–842.0–6.0?
Conjugated estrogensNaturalSteroidal5–1260–804.38.4–17.50.625–1.257.5
Diethylstilbestrol dipropionateSyntheticNonsteroidal?15–301.1–1.4???
Dienestrol diacetateSyntheticNonsteroidal3–530–602.9–4.3???
Hexestrol diacetateSyntheticNonsteroidal?45????
Note: The OID of EE is 0.1 mg/day. Footnotes: a = Very variable, often higher. b = In divided doses, 3x/day; irregular and atypical proliferation. Sources: See template.
Parenteral potencies and durations of nonsteroidal estrogens
EstrogenFormMajor brand name(s)EPD (14 days)Duration
Diethylstilbestrol (DES)Oil solution?20 mg3 mg ≈ 3 days
Diethylstilbestrol dipropionateOil solutionCyren B12.5–15 mg2.5 mg ≈ 5 days
Aqueous suspension?5 mg? mg = 21–28 days
Dimestrol (DES dimethyl ether)Oil solutionDepot-Cyren, Depot-Oestromon, Retalon Retard20–40 mg?
Fosfestrol (DES diphosphate)aAqueous solutionHonvan?<1 day
Dienestrol diacetateAqueous suspensionFarmacyrol-Kristallsuspension50 mg?
Hexestrol dipropionateOil solutionHormoestrol, Retalon Oleosum25 mg?
Hexestrol diphosphateaAqueous solutionCytostesin, Pharmestrin, Retalon Aquosum?Very short
Note: All by intramuscular injection unless otherwise noted. Footnotes: a = By intravenous injection. Sources: See template.

Antigonadotropic effects

Due to its estrogenic activity, DES has antigonadotropic effects.[55][52][56][57] That is, it exerts negative feedback on the hypothalamic–pituitary–gonadal axis (HPG axis), suppresses the secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and suppresses sex hormone production as well as gamete production or maturation in the gonads.[55][52][56][57] A study of ovulation inhibition in women found that 5 mg/day oral DES was 92% effective, with ovulation occurring in only a single cycle.[58][59] DES consistently suppresses testosterone levels in men into the castrate range (<50 ng/dL) within 1 to 2 weeks at doses of 3 mg/day and above.[55][57] Conversely, a dosage of 1 mg/day DES is unable to fully suppress testosterone levels into the castrate range in men, which instead often stabilize at just above castrate levels (>50 ng/dL).[23][52][56] However, it has also been reported that 1 mg/day DES results in approximately 50% suppression of testosterone levels, albeit with wide interindividual variability.[55] It has been said that doses of DES of less than 1 mg/day have no effect on testosterone levels.[55] However, the addition of an "extremely low" dosage of 0.1 mg/day DES to cyproterone acetate has been found to result in a synergistic antigonadotropic effect and to suppress testosterone levels into the castrate range in men.[60][61][62]

Other activities

In addition to the ERs, an in vitro study found that DES also possesses activity, albeit relatively weak, at a variety of other steroid hormone receptors.[51] Whereas the study found EC50 values of 0.18 nM and 0.06 nM of DES for the ERα and ERβ, respectively, the medication showed significant glucocorticoid activity at a concentration of 1 μM that surpassed that of 0.1 nM dexamethasone, as well as significant antagonism of the androgen, progesterone, and mineralocorticoid receptors (75%, 85%, and 50% inhibition of positive control stimulation, respectively, all at a concentration of 1 μM).[51] It also showed approximately 25% inhibition of the activation of PPARγ and LXRα at a concentration of 10 μM.[51] The researchers stated that, to the best of their knowledge, they were the first to report such actions of DES, and hypothesized that these actions could be involved in the clinical effects of DES, for instance, in prostate cancer (notably in which particularly high dosages of DES are employed).[51] However, they also noted that the importance of the activities requires further study in animal models at pharmacologically relevant doses.[51]

DES has been identified as an antagonist of all three isotypes of the estrogen-related receptors (ERRs), the ERRα, ERRβ, and ERRγ.[63]


DES is well-absorbed with oral administration.[1] With an oral dosage of 1 mg/day DES, plasma levels of DES at 20 hours following the last dose ranged between 0.9 and 1.9 ng/mL (3.4 to 7.1 nmol/L).[1] The distribution half-life of DES is 80 minutes.[1] It has no affinity for SHBG or corticosteroid-binding globulin, and hence is not bound to these proteins in the circulation.[64] The plasma protein binding of DES is greater than 95%.[2] Hydroxylation of the aromatic rings of DES and subsequent conjugation of the ethyl side chains accounts for 80 to 90% of DES metabolism, while oxidation accounts for the remaining 10 to 20% and is dominated by conjugation reactions.[2][3] Conjugation of DES consists of glucuronidation, while oxidation includes dehydrogenation into (Z,Z)-dienestrol.[1][2][3] The medication is also known to produce paroxypropione as a metabolite.[65] DES produces transient quinone-like reactive intermediates that cause cellular and genetic damage, which may explain the known carcinogenic effects of DES in humans.[1] However, other research suggests that the toxic effects of DES may simply be due to overactivation of the ERs.[66] The elimination half-life of DES is 24 hours.[1] The metabolites of DES are excreted in urine and feces.[2][3]

Sublingual administration of DES appears to have about the same estrogenic potency of oral DES in women.[67]

Intrauterine DES has been studied for the treatment of uterine hypoplasia.[68]


DES belongs to the stilbestrol (4,4'-dihydroxystilbene) group of compounds.[72] It is a nonsteroidal open-ring analogue of the steroidal estrogen estradiol.[69] DES can be prepared from anethole, which also happens to be weakly estrogenic.[72][73][71][70] Anethole was demethylated to form anol and anol then spontaneously dimerized into dianol and hexestrol, with DES subsequently being synthesized via structural modification of hexestrol.[72][73][71][70] As shown by X-ray crystallography, the molecular dimensions of DES are almost identical to those of estradiol, particularly in regards to the distance between the terminal hydroxyl groups.[70]



DES was first synthesized in early 1938 by Leon Golberg, then a graduate student of Sir Robert Robinson at the Dyson Perrins Laboratory at the University of Oxford. Golberg's research was based on work by Wilfrid Lawson at the Courtauld Institute of Biochemistry, (led by Sir Edward Charles Dodds at Middlesex Hospital Medical School now part of University College London). A report of its synthesis was published in Nature on 5 February 1938.[74][75][76]

DES research was funded by the UK Medical Research Council (MRC), which had a policy against patenting drugs discovered using public funds. Because it was not patented, DES was produced by more than 200 pharmaceutical and chemical companies worldwide.

Clinical use

DES (in tablets up to 5 mg) was approved by the United States Food and Drug Administration (FDA) on September 19, 1941 for four indications: gonorrheal vaginitis, atrophic vaginitis, menopausal symptoms, and postpartum lactation suppression to prevent breast engorgement.[76] The gonorrheal vaginitis indication was dropped when the antibiotic penicillin became available. From its very inception, the drug was highly controversial.[77][78]

In 1941, Charles Huggins and Clarence Hodges at the University of Chicago found estradiol benzoate and DES to be the first effective drugs for the treatment of metastatic prostate cancer.[79][80] DES was the first cancer drug.[81]

Orchiectomy or DES or both were the standard initial treatment for symptomatic advanced prostate cancer for over 40 years, until the GnRH agonist leuprorelin was found to have efficacy similar to DES without estrogenic effects and was approved in 1985.[82]

From the 1940s until the late 1980s, DES was FDA-approved as estrogen-replacement therapy for estrogen deficiency states such as ovarian dysgenesis, premature ovarian failure, and after oophorectomy.

In the 1940s, DES was used off-label to prevent adverse pregnancy outcomes in women with a history of miscarriage. On July 1, 1947, the FDA approved the use of DES for this indication. The first such approval was granted to Bristol-Myers Squibb, allowing use of 25 mg (and later 100 mg) tablets of DES during pregnancy. Approvals were granted to other pharmaceutical companies later in the same year.[83] The recommended regimen started at 5 mg per day in the seventh and eighth weeks of pregnancy (from first day of last menstrual period), increased every other week by 5 mg per day through the 14th week, and then increased every week by 5 mg per day from 25 mg per day in the 15th week to 125 mg per day in the 35th week of pregnancy.[84] DES was originally considered effective and safe for both the pregnant woman and the developing baby. It was aggressively marketed and routinely prescribed. Sales peaked in 1953.

In the early 1950s, a double-blind clinical trial at the University of Chicago assessed pregnancy outcomes in women who were assigned to either receive or not receive DES.[85] The study showed no benefit of taking DES during pregnancy; adverse pregnancy outcomes were not reduced in the women who were given DES. By the late 1960s, six of seven leading textbooks of obstetrics said DES was ineffective at preventing miscarriage.[83][86]

Despite an absence of evidence supporting the use of DES to prevent adverse pregnancy outcomes, DES continued to be given to pregnant women through the 1960s. In 1971, a report published in the New England Journal of Medicine showed a probable link between DES and vaginal clear cell adenocarcinoma in girls and young women who had been exposed to this drug in utero. Later in the same year, the FDA sent an FDA Drug Bulletin to all U.S. physicians advising against the use of DES in pregnant women. The FDA also removed prevention of miscarriage as an indication for DES use and added pregnancy as a contraindication for DES use.[87] On February 5, 1975, the FDA ordered 25 mg and 100 mg tablets of DES withdrawn, effective February 18, 1975.[88] The number of persons exposed to DES during pregnancy or in utero during 1940–1971 is unknown, but may be as high as 2 million in the United States. DES was also used in other countries, most notably France, the Netherlands, and Great Britain.

From the 1950s through the beginning of the 1970s, DES was prescribed to prepubescent girls to begin puberty and thus stop growth by closing growth plates in the bones. Despite its clear link to cancer, doctors continued to recommend the hormone for "excess height".[89]

In 1960, DES was found to be more effective than androgens in the treatment of advanced breast cancer in postmenopausal women.[90] DES was the hormonal treatment of choice for advanced breast cancer in postmenopausal women until 1977, when the FDA approved tamoxifen, a selective estrogen receptor modulator with efficacy similar to DES but fewer side effects.[91]

Several sources from medical literature in the 1970s and 1980s indicate that DES was used for treatment of transgender individuals.[92][93][94]

In 1973, in an attempt to restrict off-label use of DES as a postcoital contraceptive (which had become prevalent at many university health services following publication of an influential study in 1971 in JAMA) to emergency situations such as rape, an FDA Drug Bulletin was sent to all U.S. physicians and pharmacists that said the FDA had approved, under restricted conditions, postcoital contraceptive use of DES.[95]

In 1975, the FDA said it had not actually given (and never did give) approval to any manufacturer to market DES as a postcoital contraceptive, but would approve that indication for emergency situations such as rape or incest if a manufacturer provided patient labeling and special packaging as set out in a FDA final rule published in 1975.[96] To discourage off-label use of DES as a postcoital contraceptive, the FDA in 1975 removed DES 25 mg tablets from the market and ordered the labeling of lower doses (5 mg and lower) of DES still approved for other indications changed to state: "This drug product should not be used as a postcoital contraceptive" in block capital letters on the first line of the physician prescribing information package insert and in a prominent and conspicuous location of the container and carton label.[88][97] In the 1980s, off-label use of the Yuzpe regimen of certain regular combined oral contraceptive pills superseded off-label use of DES as a postcoital contraceptive.[98]

In 1978, the FDA removed postpartum lactation suppression to prevent breast engorgement from their approved indications for DES and other estrogens.[99] In the 1990s, the only approved indications for DES were treatment of advanced prostate cancer and treatment of advanced breast cancer in postmenopausal women. The last remaining U.S. manufacturer of DES, Eli Lilly, stopped making and marketing it in 1997.


In the 1970s, the negative publicity surrounding the discovery of DES's long-term effects resulted in a huge wave of lawsuits in the United States against its manufacturers. These culminated in a landmark 1980 decision of the Supreme Court of California, Sindell v. Abbott Laboratories, in which the court imposed a rebuttable presumption of market share liability upon all DES manufacturers, proportional to their share of the market at the time the drug was consumed by the mother of a particular plaintiff.

A lawsuit was filed in Boston Federal Court by 53 DES daughters who say their breast cancers were the result of DES being prescribed to their mothers while pregnant with them. Their cases survived a Daubert hearing. In 2013, the Fecho sisters who initiated the breast cancer/DES link litigation agreed to an undisclosed settlement amount on the second day of trial. The remaining litigants have received various settlements.[100]

Society and culture

Alan Turing, the ground breaking cryptographer, founder of computing science and programmable computers, who also proposed the actual theoretical model of biological morphogenesis, was forced onto the medication to induce chemical castration as a punitive "treatment" for homosexual behaviour, shortly before he died in ambiguous circumstances.[101]

Veterinary use

Canine incontinence

DES has been very successful in treating female canine incontinence stemming from poor sphincter control. It is still available from compounding pharmacies, and at the low (1 mg) dose, does not have the carcinogenic properties that were so problematic in humans.[102] It is generally administered once a day for seven to ten days and then once every week as needed.

Livestock growth promotion

The greatest usage of DES was in the livestock industry, used to improve feed conversion in beef and poultry. During the 1960s, DES was used as a growth hormone in the beef and poultry industries. It was later found to cause cancer by 1971, but was not phased out until 1979.[103][104] When DES was discovered to be harmful to humans, it was moved to veterinary use.


  1. Bruce Chabner; Dan Louis Longo (1996). Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott-Raven Publishers. p. 186. ISBN 978-0-397-51418-2. Piperazine estrone sulfate and micronized estradiol were equipotent with respect to increases in SHBG, whereas [...] DES was 28.4-fold more potent [...]. With respect to decreased FSH, [...] DES was 3.8-fold, and ethinyl estradiol was 80 to 200-fold more potent than was piperazine estrone sulfate. The dose equivalents for ethinyl estradiol (50 µg) and DES (1 mg) reflect these relative potencies.220 [...] DES, a potent synthetic estrogen (Fig. 6-12), is absorbed well after an oral dosage. Patients given 1 mg of DES daily had plasma concentrations at 20 hours ranging from 0.9 to 1.9 ng per mL. The initial half-life of DES is 80 minutes, with a secondary half-life of 24 hours.222 The principal pathways of metabolism are conversion to the glucuronide and oxidation. The oxidative pathways include aromatic hydroxylation of the ethyl side chains and dehydrogenation to (Z,Z)-dienestrol, producing transient quinone-like intermediates that react with cellular macromolecules and cause genetic damage in eukaryotic cells.223 Metabolic activation of DES may explain its well-established carcinogenic properties.224
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