By | 2011-08-17


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 Diethylstilbestrol tablets (plain tablets, enteric-coated tablets) should be stored at room temperature (15-30°C) in well-closed containers.

Diethylstilbestrol: Pharmacology

Estrogens are necessary for the normal growth and development of the female sex organs and in some species contribute to the development and maintenance of secondary female sex characteristics. Estrogens cause increased cell 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 epi-physeal 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 inhibition of 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 at the appropriate time for implantation. Diethylstilbestrol also possess antineoplastic activity against some types of neoplasias (perianal gland adenoma and prostatic hyperplasia). It affects mRNA and protein synthesis in the cell nucleus and is cell cycle nonspecific.

Diethylstilbestrol: Uses – Indications

Diethylstilbestrol has been used in estrogen responsive incontinence in spayed female dogs and in the prevention of pregnancy after mismating in female dogs and cats. Its use alone for prevention of mismating is controversial as its efficacy is in doubt.

Diethylstilbestrol 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 of the risks associated with therapy.

One author states that in small animals, “because of the alternatives and its possible side effects, estrogen is only indicated for treating mismating”. Another, states that in dogs, “owners should be routinely discouraged from having their bitches undergo abortion with estrogens.”


Diethylstilbestrol is well absorbed from the GI tract of monogastric animals. It is slowly metabolized by the liver, primarily to a glucuronide form and then excreted in the urine and feces.


Diethylstilbestrol is contraindicated during pregnancy, as it has been demonstrated 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, Diethylstilbestrol must not be used in animals to be used for human consumption.

Adverse Effects – Warnings

In cats and dogs estrogens are considered to be toxic to the bone marrow and can cause blood dyscrasias. Blood dyscrasias are more prevalent in older animals and if higher dosages are used. Initially, a thrombocytosis and/or leukocytosis may be noted, but thrombocytopenia/leukopenias will gradually develop. Changes in a peripheral blood smear may be apparent within two weeks after estrogen administration. Chronic estrogen toxicity may be characterized by a normochromic, normocytic anemia, thrombocytopenia and neutropenia. Bone marrow depression may be transient and begin to resolve within 30 – 40 days or may persist or progress to a fatal aplastic anemia. Doses of 2.2 mg/kg per day have caused death in cats secondary to bone marrow toxicity.

In cats, daily administration of Diethylstilbestrol has resulted in pancreatic, hepatic and cardiac lesions.

Estrogens may cause cystic endometrial hyperplasia and pyometra. After therapy is initiated, an open-cervix pyometra may be noted 1-6 weeks after therapy.

When used chronically in male animals, feminization may occur. In females, signs of estrus may occur and persist for 7-10 days.

Experimental administration of Diethylstilbestrol to female dogs as young as 8 months, of age have induced malignant ovarian adenocarcinomas. Doses ranging from 60 to 495 mg given over 1 month to 4 years were implicated in causing these tumors.

Diethylstilbestrol: Overdosage

Acute overdosage in humans with estrogens has resulted in nausea, vomiting and withdrawal bleeding in females. No information was located regarding acute overdose in veterinary patients, however, the reader is referred to the warnings and adverse effects listed above.

Diethylstilbestrol: 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.

Diethylstilbestrol: Doses

Doses for dogs:

For pregnancy avoidance after mismating:

a) 0.1-1 mg PO for 5 days if animal is presented 24-48 hours after coitus. If animal is presented later than 5 days post-coitus: 1 – 2 mg PO for 5 days after ECP therapy (0.044 mg/kg (ECP) IM once during 3-5 days of standing heat or within 72 hours of mismating)

For treatment of perianal gland adenomas and prostatic hyperplasias:

a) 0.1 – 1 mg PO q24-48h

b) 1 mg PO q72h; or 1.1 mg/kg once. Do not administer more than 25 mg.

For treatment of estrogen-responsive incontinence:

a) Initially 0.1-1 mg PO daily for 3-5 days, followed by maintenance therapy of approximately 1 mg PO per week. Some animals may require much higher initial dosages to obtain a response. Maximum initial doses of 0.1 – 0.3 mg/kg once daily for 7 days, then reduce to once weekly. All maintenance doses should be gradually reduced to the lowest effective dose.

b) 0.1-1 mg PO per day for 3-5 days, then 1 mg once weekly

c) 0.1-1 mg PO for 3-5 days followed by 1 mg every week or less often. Some animals may require more than 1 mg weekly to maintain.

Monitoring Parameters

When therapy is either at high dosages or chronic; see Adverse effects for more information.

Done at least monthly:

1) Packed Cell Volumes (PCV)

2) White blood cell counts (CBC)

3) Platelet counts

Baseline, one month after therapy, and repeated 2 months after cessation of therapy if abnormal:

1) Liver function tests

Client Information

Contact veterinarian if signs and symptoms of lethargy, diarrhea, vomiting, abnormal discharge from vulva, excessive water consumption and urination or abnormal bleeding occur.

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:


Human-Approved Products:

At the time of writing, no commercially available regular oral Diethylstilbestrol products are available in the USA, however compounded preparations may be available from a variety of compounding pharmacies.

Diethylstilbestrol Diphosphate Injection 50 mg/ml in 5 ml amps: .i.Stilphostrol;® (Miles) (Rx)

Diethylstilbestrol Diphosphate 50 mg Tablets; Stilphostrol® (Miles) (Rx)