Diethylstilbestrol
Also known as: Apstil · Destilbenol · Distilbene · diethylstilbestrolum · diethylstilboestrol · NSC-3070
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Primary sphincter mechanism incompetence (Option A) | 0.1-1 mg (total dose) per dog PO for 5 days followed by maintenance of 1 mg/week or a maximum of 0.1 mg/kg/week. Minimum effective dose should be used for maintenance. Do NOT give more than recommended. | PO | Once daily for 5 days, then weekly | Long-term maintenance | 🌎 NA |
| Primary sphincter mechanism incompetence (Option B - females) | 0.1-1 mg (total dose) PO once daily for 5 days, then 1 mg once a week | PO | Once daily for 5 days, then weekly | Long-term maintenance | 🌎 NA |
| Primary sphincter mechanism incompetence (Option C) | 0.5-1 mg (0.02 mg/kg; maximum dose of 1 mg) for 3-5 days as an induction dose and then periodically decreased to every other day and then to the lowest dose that will maintain continence. | PO | Daily initially, then tapered | Long-term maintenance | 🌎 NA |
| Estrus induction | DES at 5 mg/day for a tentative 7 days. The first day of vulvar swelling is designated as Day 1. Continue DES on DAY 1 and Day 2. If no effect is seen in 7 days, give DES at 10 mg/day for another tentative 7 days. If vulvar swelling and bleeding detected, DES is continued on Day 1 and Day 2. If no effect seen in these 14 days, discontinue and restart in 30 days. Once proestrus initiated, on Day 5 give 5 mg of Luteinizing hormone (LH) if obtainable. If LH unavailable, give GnRH 3.3 micrograms/kg IM and FSH 10 mg IM in its place. Bitch is bred on Day 13. | PO | Daily | 7-14 days | 🌎 NA |
| Benign prostatic hypertrophy | 0.2-1 mg total dose PO for 5 days | PO | Daily | 5 days | 🌎 NA |
- Primary sphincter mechanism incompetence (Option A): As an alternative to phenylpropanolamine.
- Primary sphincter mechanism incompetence (Option C): In difficult cases, may be used with phenylpropanolamine. Note: Conjugated estrogens (e.g., Premarin) are sometimes used as a substitute (e.g., 20 mcg/kg PO every 4 days).
- Estrus induction: Adjust dosages of LH and FSH for animal size-the above dosages are for a dog weighing 50-60 lbs.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Estrogen-responsive incontinence (females) | 0.1-1 mg (total dose) PO once daily for 5 days, then 1 mg once a week | PO | Once daily for 5 days, then weekly | Long-term maintenance | 🌎 NA |
- Estrogen-responsive incontinence (females): Doses of 2.2 mg/kg per day have caused death in cats secondary to bone marrow toxicity.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Diethylstilbestrol (DES) is a synthetic, nonsteroidal estrogen primarily used in veterinary medicine for the management of estrogen-responsive urinary incontinence in spayed female dogs. It has also been utilized for benign prostatic hypertrophy in male dogs and estrus induction.
Clinical Pearl: Due to the severe risk of bone marrow toxicity (fatal aplastic anemia) and its classification as a potential carcinogen and teratogen, DES is strictly prohibited in food-producing animals.
Because of human health concerns and market withdrawals, DES is no longer commercially available as an FDA-approved manufactured product and must be obtained through veterinary compounding pharmacies. In modern practice, safer alternatives like estriol (Incurin) or phenylpropanolamine (PPA) are often preferred as first-line therapies for sphincter mechanism incompetence.
Mechanism of action
DES acts as a potent agonist at estrogen receptors (ER-α and ER-β). Upon binding, the receptor-ligand complex translocates to the cell nucleus, where it binds to estrogen response elements (EREs) on DNA, altering mRNA transcription and subsequent protein synthesis.
- Urinary Incontinence: Estrogens upregulate the expression and sensitivity of α-adrenergic receptors in the internal urethral sphincter. This increases the sphincter's responsiveness to endogenous norepinephrine, thereby increasing resting urethral closure pressure and preventing urine leakage.
- Reproductive/Systemic Effects: Promotes growth and development of female sex organs, increases cervical/vaginal mucosal thickness, and causes endometrial proliferation. It also accelerates epiphyseal closure, increases calcium deposition in bone, and inhibits pituitary gonadotropin release via negative feedback.
Safety & warnings
Contraindications
- Food-producing animals (FDA prohibited)
- Pregnancy (teratogenic; causes fetal genitourinary malformations)
- Patients with preexisting anemias or leukopenias
- Females with estrogen-sensitive neoplasms
Adverse effects
- Bone marrow suppression (thrombocytopenia, leukopenia, fatal aplastic anemia)
- Cystic endometrial hyperplasia
- Pyometra (in intact females)
- Mammary neoplasia
- Feminization (in males)
- Signs of estrus (in females)
- Pancreatic, hepatic, and cardiac lesions (reported in cats)
- Malignant ovarian adenocarcinomas (experimental)
Precautions
WARNING: DES is strictly prohibited by the FDA for use in food animals due to carcinogenic potential.
- Bone Marrow Toxicity: Estrogens are toxic to the bone marrow in dogs and cats. Use with extreme caution in patients with preexisting hematologic abnormalities. Toxicity is dose-dependent and more common in older animals.
- Pyometra Risk: Can induce cystic endometrial hyperplasia and open-cervix pyometra in intact females 1-6 weeks after initiating therapy.
- Carcinogenicity: May induce mammary neoplasias and has been linked to malignant ovarian adenocarcinomas in experimental settings.
Drug interactions
May increase estrogen levels
May decrease metabolism of estrogens
Enhanced glucocorticoid effects may result; estrogens may alter protein binding or decrease metabolism of corticosteroids
May decrease the metabolism of estrogens
Oral anticoagulant activity may be decreased; increases in anticoagulant dosage may be necessary
May decrease estrogen concentrations
May decrease estrogen concentrations
May induce hepatic microsomal enzymes and decrease estrogen levels
Monitoring
- Packed Cell Volumes (PCV)
- White blood cell counts
- Platelet counts
- Liver function tests (at baseline, one month after therapy begins, and repeat 2 months after cessation if abnormal)
Pharmacokinetics
Absorption
Well absorbed from the GI tract of monogastric animals.
Metabolism
Slowly metabolized by the liver, primarily to a glucuronide form.
Elimination
Excreted in the urine and feces.
Overdose
Acute overdosage in humans with estrogens has resulted in nausea, vomiting, and withdrawal bleeding in females.
In veterinary patients, acute overdose information is limited, but chronic overdosage or high doses are well-documented to cause severe, potentially fatal bone marrow suppression (aplastic anemia, thrombocytopenia, neutropenia). Doses of 2.2 mg/kg per day have caused death in cats. Treatment of overdose should involve immediate discontinuation of the drug and aggressive supportive care (e.g., blood transfusions, broad-spectrum antibiotics for neutropenia).
Available products
Formulations
- Compounded oral capsules
- Compounded oral tablets
- Compounded oral suspensions
Human-labeled
- No commercially available regular oral DES products are available in the USA. Compounded preparations may be available from compounding pharmacies.
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
All commercially available DES tablets (plain tablets, enteric-coated tablets) should be stored at room temperature (15-30°C) in well-closed containers.
Client information
Diethylstilbestrol (DES) is a hormone used primarily to treat urinary incontinence (leaking urine) in spayed female dogs.
- Strict Dosing: It is critical to give this medication exactly as prescribed. Giving more than the recommended dose can lead to fatal bone marrow disease.
- Watch for Bleeding/Infection: Contact your veterinarian immediately if you notice pale gums, unexplained bruising, lethargy, weakness, or fever.
- Watch for Pyometra Signs: If your pet is an unspayed female, watch for excessive water consumption, frequent urination, or abnormal discharge from the vulva, which could indicate a severe uterine infection.
- Other Signs to Report: Diarrhea, vomiting, or signs of being in "heat" (swollen vulva, bleeding).
- Handling: Wash your hands after handling the medication, and keep it strictly out of reach of children and other pets.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.