Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a

nonsteroidal estrogen A nonsteroidal estrogen is an estrogen with a nonsteroidal chemical structure. The most well-known example is the stilbestrol estrogen diethylstilbestrol (DES). Although nonsteroidal estrogens formerly had an important place in medicine, they ha ...

medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

support for those with a history of

recurrent miscarriage Recurrent miscarriage or recurrent pregnancy loss (RPL) is the spontaneous loss of 2-3 pregnancies that is estimated to affect up to 5% of women. The exact number of pregnancy losses and gestational weeks used to define RPL differs among medic ...

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 hormonal therap ...

for

menopausal symptoms Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

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 the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

and

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

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

infertility In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...

miscarriage Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...

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 sympto ...

preeclampsia Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the new onset of high blood pressure and often a significant amount of protein in the urine or by the new onset of high blood pressure along with significant end- ...

preterm birth Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 ...

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

, infant death,

menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

prior to age 45, breast cancer,

cervical cancer Cervical cancer is a cancer arising from the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that can invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later sympt ...

, and

vaginal cancer Vaginal cancer is an extraordinarily rare form of cancer that develops in the tissue of the vagina. Primary vaginal cancer originates from the vaginal tissue – most frequently Squamous-cell carcinoma of the vagina, squamous cell carcinoma, but p ...

. While most commonly taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

, DES was available for use by other

routes Route or routes may refer to: * Air route, route structure or airway * GPS route, a series of one or more GPS waypoints * Route (gridiron football), a path run by a wide receiver * Route (command), a program used to configure the routing table * ...

as well, for instance,

vaginal In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The vaginal introit ...

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

, and by

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

. DES is an

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

, or an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

s, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

of estrogens like

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

. It is a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

and

of the

stilbestrol Stilbestrol, or stilboestrol, also known as 4,4'-dihydroxystilbene or 4,4'-stilbenediol, is a stilbenoid nonsteroidal estrogen and the parent compound of a group of more potency (pharmacology), potent nonsteroidal estrogen chemical derivative, de ...

group, and differs from the

natural Nature is an inherent character or constitution, particularly of the ecosphere or the universe as a whole. In this general sense nature refers to the laws, elements and phenomena of the physical world, including life. Although humans are part ...

estrogen

. Compared to estradiol, DES has greatly improved

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

when taken by mouth, is more resistant to

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

, and shows relatively increased effects in certain parts of the body like the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

. These differences result in DES having an increased risk of

blood clot A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...

s, 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 clas ...

, a rare vaginal tumor, in those who had been exposed to this medication ''

in utero The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bir ...

''. The

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

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 including infertility. The United States

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

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 Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

effects of DES, it has largely been discontinued and is now mostly no longer marketed for human treatment.

Medical uses

DES has been used in the past for the following indications: *

Recurrent miscarriage Recurrent miscarriage or recurrent pregnancy loss (RPL) is the spontaneous loss of 2-3 pregnancies that is estimated to affect up to 5% of women. The exact number of pregnancy losses and gestational weeks used to define RPL differs among medic ...

Menopausal hormone therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...

for the treatment of

menopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s such as

hot flash Hot flushes are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from t ...

es and

vaginal atrophy Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to low estrogen levels. Symptoms may include pain during penetrative sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It ...

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 hormonal therap ...

for

hypoestrogenism 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 ...

(e.g.,

gonadal dysgenesis Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo. One type of gonadal dysgenesis is the devel ...

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

, and after

oophorectomy Oophorectomy (; from Greek , , 'egg-bearing' and , , 'a cutting out of'), historically also called ''ovariotomy'', is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term is mostly used in reference ...

) *

Postpartum The postpartum (or postnatal) period begins after childbirth and is typically considered to last for six to eight weeks. There are three distinct phases of the postnatal period; the acute phase, lasting for six to twelve hours after birth; the ...

lactation suppression to prevent or reverse

breast engorgement Breast engorgement occurs in the mammary glands due to expansion and pressure exerted by the synthesis and storage of breast milk. It is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and cu ...

Gonorrhea Gonorrhoea or gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium ''Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Gonorrhea is spread through sexual c ...

vaginitis Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy. The three mai ...

(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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

) *

Prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

and

* Prevention of

tall stature Human height or stature is the distance from the bottom of the feet to the top of the head in a human body, standing erect. It is measured using a stadiometer, in centimetres when using the metric system or SI system, or feet and inches when us ...

in tall adolescent girls * Treatment of

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

in girls and women * As an emergency postcoital contraceptive * As a means of

chemical castration Chemical castration is castration via anaphrodisiac drugs, whether to reduce libido and sexual activity, management of cancer, to treat cancer, or otherwise. Unlike orchiectomy, surgical castration, where the gonads are removed through an incision ...

for treating

hypersexuality Hypersexuality is a proposed medical condition said to cause unwanted or excessive sexual arousal, causing people to engage in or think about sexual activity to a point of distress or impairment., according to the website of ''Psychology Toda ...

and

paraphilia A paraphilia is an experience of recurring or intense sexual arousal to atypical objects, places, situations, fantasies, behaviors, or individuals. It has also been defined as a sexual interest in anything other than a legally consenting human ...

s and

sex offender A sex offender (sexual offender, sex abuser, or sexual abuser) is a person who has committed a Sex and the law, sex crime. What constitutes a sex crime differs by culture and legal jurisdiction. The majority of convicted sex offenders have convi ...

s * Prevention of the

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

flare at the start of

gonadotropin-releasing hormone agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the tre ...

(GnRH agonist) therapy *

Feminizing hormone therapy Feminizing hormone therapy, also known as transfeminine hormone therapy, is a form of Transgender_health_care#Gender-affirming_care , gender-affirming care and a gender-affirming hormone therapy , gender-affirming hormone therapy to change t ...

for

transgender women A trans woman or transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity and may experience gender dysphoria (distress brought upon by the discrepancy between a person's gender identity and their ...

DES was used at a dosage of 0.2 to 0.5 mg/day in

menopausal hormone therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...

. Interest in the use of DES to treat prostate cancer continues today. However, use of

bioidentical Bioidentical hormone replacement therapy (BHRT), also known as bioidentical hormone therapy (BHT) or natural hormone therapy, is the use of hormones that are identical on a molecular level with endogenous hormones in hormone replacement therapy. ...

parenteral In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

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

instead of DES for breast cancer. Oral DES at 0.25 to 0.5 mg/day is effective in the treatment of

es in men undergoing

androgen deprivation therapy Androgen deprivation therapy (ADT), also called androgen ablation therapy or androgen suppression therapy, is an antihormone therapy whose main use is in treating prostate cancer. Prostate cancer cells usually require androgen, androgen hormones, ...

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 effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s including

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

, abdominal discomfort,

headache A headache, also known as cephalalgia, 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 (mood), depression in those with severe ...

, and

bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, pressu ...

(incidence of 15–50%).

Breast changes and feminization

The

pigmentation A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly insoluble and chemically unreactive in water or another medium; in contrast, dyes are colored substances which are soluble or go in ...

of the

breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

areolae The human areola (''areola mammae'', or ) is the pigmented area on the breast around the nipple. More generally, an areola is a small circular area on the body with a different histology from the surrounding tissue, or other small circular ar ...

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

. The mechanism of the difference is unknown.

Progestogen Progestogens, also sometimes written progestins, 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 progestoge ...

s like

hydroxyprogesterone caproate Hydroxyprogesterone caproate, sold under the brand name Delalutin among others, is a medication used to reduce the risk of preterm birth in women pregnant with one baby who have a history of spontaneous preterm birth. In March 2023, the manuf ...

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 Gynecomastia (also spelled gynaecomastia) is the non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (10 Novemb ...

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

therapy for those with

, it has been associated with considerable

cardiovascular In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

morbidity A disease is a particular abnormal condition that adversely affects the structure or function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical conditions that are asso ...

and mortality. 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 Venous thrombosis is the blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off ( embolizes) and flows to the lun ...

. A 3 mg/day dosage of DES has been associated with an incidence of

thromboembolism Thromboembolism is a condition in which a blood clot (thrombus) breaks off from its original site and travels through the bloodstream (as an embolus) to obstruct a blood vessel, causing tissue ischemia and organ damage. Thromboembolism can affe ...

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 Orchiectomy (also named orchidectomy) is a surgery, surgical procedure in which one or both testicles are removed. The surgery can be performed for various reasons: *treatment for testicular cancer *as part of gender-affirming surgery for trans ...

alone).

Other long-term effects

DES has been linked to a variety of long-term adverse effects in women who were treated with it during pregnancy, and/or in their offspring, including increased risk of the following: * vaginal clear-cell adenocarcinoma * vaginal adenosis * T-shaped uterus *

uterine fibroids Uterine fibroids, also known as uterine leiomyomas, fibromyoma or fibroids, are leiomyoma, benign smooth muscle tumors of the uterus, part of the female reproductive system. Most people with fibroids have no symptoms while others may have dysm ...

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 weakn ...

hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...

* intersexual gestational defects * depression A comprehensive animal study in 1993 found a

plethora {{Short pages monitor