Diethylstilbestrol for Veterinary Use

Therapeutic Class: Synthetic Estrogen (nonsteroidal)

Species: Dogs and cats

May Be Prescribed For: Urinary incontinence, mismating, prostatic hypertrophy, treatment of estrogen-responsive neoplasia, and induction of heat.

Diethylstilbestrol (DES) is a synthetic estrogen. Estrogen is one of the primary ovarian hormones and the pharmacologic actions of DES mimic those of estrogen. These include development and maintenance of female sexual organs and secondary sex-characteristics. Estrogens affect the release of pituitary hormones, affecting lactation, ovulation androgen, and other hormone secretion. They have some mild anabolic effects and have multiple effects on the skeletal system including increasing calcium deposition, bone formation, and accelerating epiphyseal-closure. Estrogen also can increase sodium and water retention. DES is well-absorbed from the gastrointestinal tract.

DES is used primarily to treat urinary incontinence in spayed females. Estrogens increase urethral tone and help to prevent leaking or dribbling of urine. DES usually is effective for this purpose and the risk of side effects is relatively low due to the small dose. DES may be used with the alpha-agonist phenylpropanolamine. These drugs behave in a synergistic fashion.

DES has been used to prevent pregnancy due to accidental breeding or mismating in dogs and cats. It generally is not recommended for this purpose, as it is not very effective. DES is used in the management or treatment of prostatic hypertrophy. The definitive and preferred treatment for prostatic hypertrophy is castration but in cases where that is not an option, a short course of DES has been shown to reduce prostatic secretion markedly for up to two months. The risk of adverse effects increases with multiple treatments. DES also is used to treat certain hormonally responsive tumors including perianal gland adenoma, although this use is controversial due to side effects. DES also has been used experimentally in combination with other hormones for inducing estrus. Different protocols combine DES with LH, FSH and HCG. This work is still experimental and not widely used clinically.

• The most-serious side-effect of estrogen therapy is bone-marrow suppression and toxicity that may progress to a fatal aplastic-anemia. Estrogen toxicity manifests itself first by a leukocytosis, followed by bone-marrow depression with anemia, thrombocytopenia, and leukopenia. Blood dyscrasia and changes in the peripheral blood smear may be evident by two weeks. Although this serious adverse effect is more common after large or repeated doses, it may occur at the recommended dose. Side effects are more common in older animals. Because of the potential toxic side-effects of estrogen use, it is always important to use the lowest effective dose for the shortest period of time.

• Other side-effects include signs of estrus, lethargy, diarrhea, vomiting, vaginal discharge, pyometra, polydipsia, polyuria, and feminization of male dogs.

• DES and other estrogens should not be used during pregnancy as it has been shown to cause fetal malformations.

• Daily administration of DES in cats resulted in lesions in the pancreas, liver and heart. Estrogens have been shown to be carcinogenic in laboratory animals.

• Rifampin, phenobarbital and phenylbutazone may decrease the activity of DES due to microsomal enzyme induction.

• DES and other estrogens may enhance corticosteroid activity. The corticosteroid dose may need to be adjusted.

• DES and other estrogens may decrease the activity of anticoagulants.

Overdose in humans resulted in nausea, vomiting and bleeding.