Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.


DIETHYLSTILBESTROL, (DES)

Chemistry - A synthetic nonsteroidal estrogen agent, diethylstilbestrol occurs as an odorless, white, crystalline powder with a melting range of 169°-175°C. It is practically insoluble in water;soluble in alcohol or fatty oils. Diethylstilbestrol is also known as DES or Stilbestrol.

Storage, Stability, Compatibility

All commercially available DES tablets (plain tablets, entericcoated tablets) should be stored at room temperature (15-30°C) in well-closed containers.

Pharmacology - DIETHYLSTILBESTROL, (DES)

Estrogens are necessary for the normal growth and development of the female sexorgans and in some species contribute to the development and maintenance of secondary female sexcharacteristics. Estrogens cause increased cel height and secretions of the cervical mucosa, thickening of the vaginal mucosa, endometrial proliferation and increased uterine tone.
Estrogens have effects on the skeletal system. They increase calcium deposition, accelerate epiphyseal closure and increase bone formation. Estrogens have a slight anabolic effect and can increase sodium and water retention.
Estrogens affect the release of gonadotropins from the pituitary gland, which can cause inhibitionof lactation, inhibition of ovulation and inhibition of androgen secretion.
Excessive estrogen will delay the transport of the ovum and prevent it from reaching the uterus atthe appropriate time for implantation. DES also possess antineoplastic activity against some typesof neoplasias (perianal gland adenoma and prostatic hyperplasia). It affects mRNA and proteinsynthesis in the cell nucleus and is cell cycle nonspecific.
Uses, Indications - DES has been used in estrogen responsive incontinence in spayed female dogsand in the prevention of pregnancy after mismating in female dogs and cats. Its use alone forprevention of mismating is controversial as its efficacy is in doubt.
DES is used in canine medicine for the treatment of certain estrogen-responsive neoplasias (see
Pharmacology and Doses below). The use of DES for these conditions is controversial because ofthe risks associated with therapy.
One author (Teske 1986) states that in small animals, "because of the alternatives and its possibleside effects, estrogen is only indicated for treating mismating". Another (Olson et al. 1986), statesthat in dogs, "owners should be routinely discouraged from having their bitches undergo abortionwith estrogens."

Pharmacokinetics - DIETHYLSTILBESTROL, (DES)

DES is well absorbed from the GI tract of monogastric animals. It is slowlymetabolized by the liver, primarily to a glucuronide form and then excreted in the urine and feces.
Contraindications/Precautions - DES is contraindicated during pregnancy, as it has beendemonstrated to cause fetal malformations of the genitourinary system.
Estrogens have been documented to be carcinogenic at low levels in some laboratory animals.
Because of the potential for danger to the public health, DES must not be used in animals to beused for human consumption.

Adverse Effects, Warnings

In cats and dogs estrogens are considered to be toxic to the bonemarrow and can cause blood dyscrasias. Blood dyscrasias are more prevalent in older animals andif higher dosages are used. Initially, a thrombocytosis and/or leukocytosis may be noted, butthrombocytopenia/leukopenias will gradually develop. Changes in a peripheral blood smear may beapparent within two weeks after estrogen administration. Chronic estrogen toxicity may becharacterized by a normochromic, normocytic anemia, thrombocytopenia and neutropenia. Bonemarrow depression may be transient and begin to resolve within 30 - 40 days or may persist orprogress to a fatal aplastic anemia. Doses of 2.2 mg/kg per day have caused death in cats secondaryto bone marrow toxicity.
In cats, daily administration of DES has resulted in pancreatic, hepatic and cardiac lesions.
Estrogens may cause cystic endometrial hyperplasia and pyometra. After therapy is initiated, anopen-cervix pyometra may be noted 1-6 weeks after therapy.
When used chronically in male animals, feminization may occur. In females, signs of estrus mayoccur and persist for 7-10 days.
Experimental administration of DES to female dogs as young as 8 months. of age have inducedmalignant ovarian adenocarcinomas. Doses ranging from 60 to 495 mg given over 1 month to 4years were implicated in causing these tumors.
Overdosage - Acute overdosage in humans with estrogens has resulted in nausea, vomiting andwithdrawal bleeding in females. No information was located regarding acute overdose in veterinarypatients, however, the reader is referred to the warnings and adverse effects listed above.

Drug Interactions

Rifampin may decrease estrogen activity if administered concomitantly. This is presumably due to microsmal enzyme induction with resultant increase in estrogen metabolism.
Other known enzyme inducers (e.g., phenobarbital, phenylbutazone, etc.), may have a similar effect, but clinical significance is unclear.
Enhanced glucocorticoid effects may result if estrogens are used concomitantly with corticosteroid agents. It has been postulated that estrogens may either alter the protein binding of corticosteroids and/or decrease their metabolism. Corticosteroid dosage adjustment may be necessary when estrogen therapy is either started or discontinued.
Oral anticoagulant activity may be decreased if estrogens are administered concurrently.
Increases in anticoagulant dosage may be necessary if adding estrogens.
Drug/Laboratory Interactions - Estrogens in combination with progestins (e.g., oral contraceptives) have been demonstrated in humans to increase thyroxine-binding globulin (TBG) with resultant increases in total circulating thyroid hormone. Decreased T3 resin uptake also occurs, but free T4 levels are unaltered.
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