This article delves into the use of Diethylstilbestrol (DES) and Estriol, two estrogen derivatives, in veterinary medicine, focusing on their applications, mechanisms of action, and potential adverse effects, particularly in dogs. While DES, a nonsteroidal estrogen, was once explored for various applications, its use is now significantly restricted due to serious health concerns in humans, including carcinogenicity and teratogenicity. Estriol, a natural estrogen, presents a safer alternative for specific conditions, primarily estrogen-responsive urinary incontinence in spayed female dogs. Understanding the distinct properties and risks associated with each compound is crucial for veterinarians and pet owners.
Diethylstilbestrol (DES): Applications and Risks
Diethylstilbestrol is a synthetic estrogen that mimics the effects of natural estradiol. While available in some countries through veterinary compounding pharmacies, its commercial availability in the United States is prohibited due to its known carcinogenic and teratogenic effects in humans. In dogs, DES is orally bioavailable, reaching peak plasma concentrations within an hour and possessing an elimination half-life of 24 hours, attributed to enterohepatic recirculation.
The mechanism of action for DES in managing certain conditions involves sensitizing the urethral sphincter to alpha-adrenergic stimulation, making it synergistic with alpha-adrenergic agonists. The administration typically involves a daily loading dose for 7–10 days, followed by a reduction to once-weekly dosing to mitigate toxic effects.
However, the use of DES is associated with significant adverse effects in dogs. Bone marrow suppression is a primary concern, manifesting initially as thrombocytopenia and potentially leading to fatal aplastic anemia. Hematopoietic toxicity, while rarer, can also occur in cats. Other adverse effects observed in dogs include alopecia, cystic ovaries, cystic endometrial hyperplasia, pyometra, prolonged estrus, and infertility. These risks are notably reduced when DES is administered only once weekly in spayed female dogs. Due to its association with carcinogenicity, the use of DES is banned in food animals in most countries, and the FDA in the US specifically prohibits its extralabel use in such animals.
Estriol: A Safer Alternative for Urinary Incontinence
Estriol, a naturally occurring estrogen, exhibits a high affinity for receptors in the lower urogenital tract. Its primary approved use in veterinary medicine is for treating estrogen-responsive urinary incontinence in ovariohysterectomized female dogs in the US, Australia, and the UK. Estriol works by increasing urethral resting tone in females.
Following oral administration, estriol is rapidly absorbed and becomes highly protein-bound in plasma. Like other estrogens, it is widely distributed, with higher concentrations found in sex hormone target organs. The liver conjugates estriol, which is then excreted via urine. In dogs, the elimination half-life of estriol is approximately 8–12 hours.
While generally considered safer than DES, estriol can still cause adverse effects. These include anorexia, emesis, polydipsia, anxiety, aggression, lethargy, hypersalivation, swollen vulvae, estrous behavior, sexual attractiveness, and mammary hyperplasia. These estrogenic effects typically resolve with a reduction in dosage. It is important to note that estriol should not be used concurrently with other estrogens. Contraindications for its use include polyuria and polydipsia, pregnancy, lactation, and age less than 1 year.
Conclusion and Considerations
The use of estrogen derivatives like Diethylstilbestrol and Estriol in veterinary practice requires careful consideration of their efficacy, mechanism of action, and, crucially, their potential side effects. Diethylstilbestrol, due to its significant risks, has largely been phased out for most applications, especially with the availability of safer alternatives. Estriol offers a valuable therapeutic option for urinary incontinence in spayed female dogs, though vigilance for potential adverse reactions is still necessary. Veterinarians must weigh the benefits against the risks, adhere to approved dosages and administration protocols, and counsel pet owners about possible side effects to ensure the well-being of their animal companions.
