Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with a history of recurrent miscarriage,

hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...

for menopausal symptoms and

estrogen deficiency Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiov ...

, treatment of

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

and breast cancer, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported on adverse health outcomes linked to DES including

infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...

miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...

ectopic pregnancy Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. ...

, preeclampsia, preterm birth,

stillbirth Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...

infant death Infant mortality is the death of young children under the age of 1. This death toll is measured by the infant mortality rate (IMR), which is the probability of deaths of children under one year of age per 1000 live births. The under-five morta ...

, menopause prior to age 45, breast cancer,

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...

, and vaginal cancer. While most commonly taken by mouth, DES was available for use by other

routes Route or routes may refer to: * Route (gridiron football), a path run by a wide receiver * route (command), a program used to configure the routing table * Route, County Antrim, an area in Northern Ireland * ''The Route'', a 2013 Ugandan film * Ro ...

as well, for instance,

vaginal In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hyme ...

, topical, and by injection. DES is an estrogen, or an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the estrogen receptors, the biological target of estrogens like estradiol. It is a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

and nonsteroidal estrogen of the stilbestrol group, and differs from the natural estrogen estradiol in various ways. 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. These differences result in DES having an increased risk of blood clots, cardiovascular issues, and certain other adverse effects. DES was discovered in 1938 and introduced for medical use in 1939. 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. In 1971, DES was shown to cause

clear-cell carcinoma Clear-cell carcinoma, also known as clear-cell adenocarcinoma and mesonephroma, is an epithelial-cell-derived carcinoma characterized by the presence of clear cells observed during histological, diagnostic assessment. This form of cancer is classi ...

, a rare

vaginal tumor Vaginal tumors are neoplasms (tumors) found in the vagina. They can be benign or malignant. A neoplasm is an abnormal growth of tissue that usually forms a tissue mass. Vaginal neoplasms may be solid, cystic or of mixed type. Vaginal cancers arise ...

, in those who had been exposed to this medication '' in utero''. The United States Food and Drug Administration subsequently withdrew approval of DES as a treatment for pregnant women. 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. The United States National Cancer Institute recommends children 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". Since the discovery of the toxic effects of DES, it has largely been discontinued and is now mostly no longer marketed.

Medical uses

DES has been used in the past for the following indications: * Recurrent miscarriage in pregnancy * Menopausal hormone therapy for the treatment of menopausal

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s such as hot flashes and

vaginal atrophy Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to not enough estrogen. Symptoms may include pain with sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It generally does no ...

Hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...

for hypoestrogenism (e.g., gonadal dysgenesis,

premature ovarian failure Primary ovarian insufficiency (POI) (also called premature ovarian insufficiency, premature menopause, and premature ovarian failure) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of fol ...

, and after oophorectomy) * Postpartum

lactation suppression Lactation suppression refers to the act of suppressing lactation by medication or other non pharmaceutical means. The breasts may become painful when engorged with milk if breastfeeding is ceased abruptly, or if never started. This may occur if a ...

to prevent or reverse breast engorgement * Gonorrheal vaginitis (discontinued following the introduction of the

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

) *

Prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

and breast cancer * Prevention of tall stature in tall adolescent girls * Treatment of acne in girls and women * As an emergency postcoital contraceptive * As a means of chemical castration for hypersexuality and paraphilias in men and sex offenders * Prevention of the testosterone flare at the start of gonadotropin-releasing hormone agonist (GnRH agonist) therapy * Feminizing hormone therapy for transgender women DES was used at a dosage of 0.2 to 0.5 mg/day in menopausal hormone therapy. Interest in the use of DES to treat prostate cancer continues today. However, use of bioidentical parenteral estrogens like polyestradiol phosphate has been advocated in favor of oral synthetic estrogens like DES due to their much lower risk of cardiovascular toxicity. In addition to prostate cancer, some interest in the use of DES to treat breast cancer continues today as well. However, similarly to the case of prostate cancer, arguments have been made for the use of bioidentical estrogens like estradiol instead of DES for breast cancer. Oral DES at 0.25 to 0.5 mg/day is effective in the treatment of hot flashes in men undergoing androgen deprivation therapy for prostate cancer. Although DES was used to support pregnancy, it was later found not to be effective for this use and to actually be harmful.

Side effects

At more than 1 mg/day, DES is associated with high rates of side effects including nausea, vomiting, abdominal discomfort,

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, and bloating (incidence of 15–50%).

Breast changes and feminization

The pigmentation of the breast areolae are often very dark and almost black with DES therapy. The pigmentation that occurs with synthetic estrogens such as DES is much greater than with natural estrogens such as estradiol. The mechanism of the difference is unknown.

Progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

s like hydroxyprogesterone caproate have been reported to reduce the nipple hyperpigmentation induced by high-dose estrogen therapy. In men treated with it for prostate cancer, DES has been found to produce high rates of gynecomastia (breast development) of 41 to 77%.

Blood clots and cardiovascular issues

In studies of DES as a form of

high-dose estrogen High-dose estrogen (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of a progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and p ...

therapy for those with

, it has been associated with considerable cardiovascular morbidity and

mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...

. The risk is dose-dependent. A dosage of 5 mg/day DES has been associated with a 36% increase in non-cancer-related (mostly cardiovascular) deaths. In addition, there is an up to 15% incidence of venous thromboembolism. 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%. 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).

Other long-term effects

DES has been linked to a variety of long-term adverse effects, such as increased risk of *

vaginal clear-cell adenocarcinoma Clear-cell adenocarcinoma (CCA) of the vagina or cervix is a rare adenocarcinoma often linked to prenatal exposure to diethylstilbestrol (DES), a drug which was prescribed in high-risk pregnancy. Presentation After age 30 it was thought that wo ...

* vaginal adenosis *

T-shaped uterus A t-shaped uterus is a type of uterine malformation wherein the uterus is shaped resembling the letter T. This is typically observed in DES-exposed women. It is recognised in the ESHRE/ESGE classification, and is associated with failed implantati ...

* uterine fibroids *

cervical weakness Cervical weakness, also called cervical incompetence or cervical insufficiency, is a medical condition of pregnancy in which the cervix begins to dilate (widen) and efface (thin) before the pregnancy has reached term. Definitions of cervical weak ...

* breast cancer *

* hypogonadism *

intersexual Intersex people are individuals born with any of several Sexual characteristics, sex characteristics including chromosome patterns, gonads, or sex organ, genitals that, according to the Office of the United Nations High Commissioner for Hum ...

gestational defects * depression, * and others, in women who were treated with it during pregnancy, and/or in their offspring. A comprehensive animal study in 1993 found a

plethora {{Short pages monitor