Diethylstilbestrol: Indications, Contraindications, Administration, Adverse Reactions, Interactions, Precautions and Warnings

It is a synthetic estrogen that, among other uses, is used to reduce the risk of miscarriage and prostate problems.


Diethylstilbestrol is indicated for the treatment of:

  • Metastatic breast carcinoma in postmenopausal women and appropriately selected men.
  • Metastatic carcinoma of the prostate (hormone dependent tumor).

Contraindications of diethylstilbestrol

Estrogens should not be used in women or men with any of the following conditions:

  • Breast cancer, suspected or confirmed, except in appropriately selected and treated patients for metastatic disease.
  • Estrogen-dependent, suspected or confirmed neoplasm.
  • Suspicious or confirmed pregnancy.
  • Vaginal bleeding, thrombophlebitis, and / or current or recurrent thromboembolic disorders.
  • Severe liver disease, heart failure, kidney failure, porphyria .

Diethylstilbestrol is classified in pregnancy risk category X, because in studies in animals and pregnant women, the drug caused fetal abnormalities, with clear evidence of risk to the fetus that is greater than any possible benefit to the patient.

This medicine should not be used by women who are pregnant or who may become pregnant during treatment.

Administration of diethylstilbestrol

In cases of inoperable and progressive prostate cancer:

Initial dose

  • 1 to 3 mg / day initially, increased in advanced cases, as needed, subsequently reducing the dose to 1 mg daily.

Maintenance dose

  • Doses in prostatic carcinoma reach maximum effect with maintenance of 1 mg / day; larger doses do not increase efficacy.

In cases of inoperable and progressive breast carcinoma:

  • In appropriately selected men and in women in the postmenopausal phase it is 15 mg (base) / day of diethylstilbestrol (active substance) 1mg tablets.

Patients with an intact uterus should be carefully monitored for signs of endometrial cancer, and appropriate measures should be taken to exclude the possibility of other neoplasms in the occurrence of persistent or recurrent abnormal vaginal bleeding.

Maximum daily limit

  • 15 mg / day.

This medicine should not be split or chewed.

Adverse reactions

Diethylstilbestrol may induce an increased risk of neoplasms, biliary diseases, and thromboembolic diseases; Its side effects are similar to those of oral contraceptives and are described below in decreasing order of frequency:


Chest pain, breast enlargement, edema of the lower extremities, upper extremities, weight gain or loss of weight edema, nausea, anorexia, dysmenorrhea, abdominal pain, enlargement of the abdomen.


Bronchitis, gastritis, diarrhea, vomiting, endometrial hyperplasia, vaginal discharge, changes in libido, dizziness, headache changes, migraine.


Retinal thrombosis, thromboembolism , pulmonary embolism, amenorrhea, abnormal vaginal bleeding, breast tumors, galactorrhea, breast cancer, endometrial cancer, ovarian cancer, back pain, biliary tract obstruction, hepatitis, hypertension, stroke, acute myocardial infarction, urticaria.

Drug interaction of diethylstilbestrol

The simultaneous administration of rifampicin, certain barbiturates and anticonvulsants (such as hydantoins) can compromise the effectiveness of the treatment due to the enzyme induction and the acceleration of the hepatic degradation of diethylstilbestrol.

Concomitant use of bromocriptine increases the frequency of amenorrhea; administration with cyclosporine determines an increase in plasma concentrations of this immunosuppression and an increased risk of hepatocellular and nephrotoxicity.

Concomitant administration with corticosteroids may increase the toxic effects of these drugs. Concomitant administration of hepatotoxic drugs such as dantrolene may increase the risk of hepatotoxicity.

General precautions

It is necessary to make a complete medical and family history of the patient, before the start of the administration of estrogen therapy such as diethylstilbestrol; Your blood pressure will need to be checked and your breasts, abdomen, and pelvic organs examined, and you may need Pap tests.

As a general rule, estrogen should not be prescribed for more than 1 year without another physical examination.

Fluid retention

Estrogens can cause some degree of fluid retention and therefore the conditions that could be influenced by this retention, such as asthma, epilepsy, migraine, and heart or kidney disease, require careful observation.

Some patients may develop undesirable manifestations of excessive estrogen stimulation, such as abnormal or excessive uterine bleeding, mastodynia, breast enlargement, etc. In men, gynecomastia can occur.

Patients with a history of depression should be watched carefully.

Pre-existing uterine leiomyomas can enlarge with the use of estrogens.

If jaundice occurs in any patient receiving estrogen, the drug should be discontinued during investigation of the cause.

Estrogens can be insufficiently metabolized in patients with impaired liver function, and must be administered with care under these conditions.

Estrogens influence calcium and phosphorus metabolism and should be used with caution in patients with diseases associated with altered calcium metabolism and bone disease or in those with renal failure.

Pregnancy and breastfeeding

Do not use this product during pregnancy or while breastfeeding.

Diethylstilbestrol is a carcinogen that crosses the placental barrier and can cause neoplasms and abnormalities in the reproductive system of offspring. It is also considered an endocrine disruptor, capable of altering the hormonal response in various target tissues of the reproductive system.

Daughters of women who received diethylstilbestrol during pregnancy are at increased risk of developing clear cell adenocarcinoma of the cervix and vagina, structural abnormalities of the reproductive tract, infertility, pregnancy complications, and breast neoplasia after 40 years.

Children of women who received diethylstilbestrol during pregnancy are at increased risk of developing non-neoplastic epididic cysts and possibly genital abnormalities (cryptorchidism, hypospadia).

Studies in rodents demonstrated transgenerational effects of diethylstilbestrol, that is, deleterious effects in the third generation of offspring, which were not directly exposed to the compound, but which may be affected by the fact that diethylstilbestrol has modified the DNA of their parents.

This medicine should not be used by women who are pregnant or who may become pregnant during treatment.


Due to the effects of estrogens on epiphyseal closure, they should be used carefully in patients in whom bone growth is not complete.


Induction of malignant neoplasms

In some species of animals, the continuous and prolonged administration of natural or synthetic estrogens increases the frequency of carcinomas of the breast, cervix, vagina, kidneys and liver. There are reports that long-term use of estrogen may increase the risk of endometrial carcinoma in postmenopausal women.

Women exposed to diethylstilbestrol during pregnancy have an increased risk of developing breast cancer.

Caution is advised when estrogens are prescribed for women with a family history of breast cancer or for those who have breast nodules, fibrocystic breast disease, or abnormal mammograms.

Gallbladder disease

A 2 to 3-fold increased risk of gallbladder disease has been described in postmenopausal women treated with estrogen.

Regarding effects similar to those caused by estrogen-progesterone-containing oral contraceptives, there are several serious adverse events associated with the use of oral contraceptives.

However, most of them were not documented as a consequence of postmenopausal estrogen treatment, which may reflect the comparatively lower doses of estrogen used in postmenopausal women.

These adverse reactions are expected to occur more likely after administration of higher doses of estrogen, used for the treatment of prostate or breast cancer.

In fact, it has been shown that there is an increased risk of thrombosis with the administration of estrogens for prostate cancer in men.

Thromboembolic disease

It is well established that women in contraceptive use have an increased risk of various thromboembolic diseases, such as thrombophlebitis, pulmonary embolism, stroke and myocardial infarction.

Cases of retinal thrombosis, mesenteric thrombosis, and optic neuritis were reported in patients using contraceptives.

There is evidence that the risk of various adverse reactions is related to the dose of the drug. An increased risk of post-surgical thromboembolic complications was also reported in patients using oral contraceptives.

If feasible, estrogen treatment should be discontinued at least 4 weeks before surgeries that are associated with an increased risk of thromboembolism or that require long periods of immobilization.

Estrogens should not be used in people with active thrombophlebitis or thromboembolic disorders, and they should not be used (except in the treatment of malignancies) in people with a history of such disorders associated with estrogen treatment.

Estrogens must be administered with care to patients with cerebrovascular disease or coronary artery disease.

Liver adenoma

Benign hepatic adenomas appear to be associated with the use of oral contraceptives. Although these adenomas are benign and rare, they can rupture and cause death from intra-abdominal bleeding.

These lesions have not yet been described in combination with other estrogen or progestin preparations, but should be considered when abdominal pain and tenderness, abdominal mass, or hypovolemic shock are present in people on estrogen therapy.

Hepatocellular carcinoma has also been reported in women taking contraceptives.


Elevated blood pressure is not common in women using oral contraceptives; in most cases, blood pressure returns to normal with discontinuation of the drug.

There are reports that this can occur with the use of estrogens in menopause; blood pressure must be controlled during estrogen treatment, especially in high doses.

Impaired glucose tolerance

Decreased glucose tolerance has been observed in a significant percentage of patients treated with estrogen-containing oral contraceptives.

For this reason, patients with diabetes mellitus must be carefully monitored during the reception of estrogen.


Administration of estrogens can lead to severe hypercalcemia in patients with breast cancer and bone metastases. If this occurs, the drug should be discontinued and appropriate steps taken to reduce the calcium.