Urinary incontinence is commonly due to urethral sphincter incompetence. It is most common in large-breed spayed female dogs (11%–20% incidence); however, it can occur in sexually intact females, male dogs, and cats. Concentrations of 17-beta-estradiol decrease after ovariohysterectomy in bitches, resulting in the deterioration of urethral closure within 3–6 months.
Currently, no drugs are approved to treat incontinence in animals, and most of the human products historically used have been removed from the market because of toxicity concerns. Some estrogen compounds and alpha-adrenergic receptor agonists may still be available to veterinarians through compounding pharmacies
Estrogens for Treatment of Urinary Incontinence in Animals
Diethylstilbestrol is a nonsteroidal estrogen derivative that closely resembles the natural estrogen estradiol. Veterinary products are available in some countries; otherwise, diethylstilbestrol is available through veterinary compounding pharmacies. In the US, diethylstilbestrol is not commercially available, because of its carcinogenic and teratogenic effects in humans.
Diethylstilbestrol is orally bioavailable and reaches peak plasma concentrations in 1 hour in dogs; it has an elimination half-life of 24 hours because of enterohepatic recirculation. Estrogens sensitize the urethral sphincter to alpha-adrenergic stimulation; therefore, diethylstilbestrol treatment is synergistic with alpha-adrenergic agonists.
Diethylstilbestrol is administered at a daily loading dose for 7–10 days and then decreased to once-weekly dosing, if possible, to avoid toxic effects. Treated dogs are susceptible to bone marrow suppression from estrogen, typified by early thrombocytopenia (see Platelet Disorders) and potentially fatal aplastic anemia. Hematopoietic toxicity occurs rarely in cats.
Other adverse effects of diethylstilbestrol in dogs include alopecia, cystic ovaries, cystic endometrial hyperplasia, pyometra, prolonged estrus, and infertility. When it is administered once weekly in spayed female dogs, adverse effects from diethylstilbestrol are rare. Because of an association with carcinogenicity, diethylstilbestrol is banned for use in food animals in most countries. In the US, the FDA prohibits extralabel use in food-producing animals.
Estriol is a natural estrogen that has high affinity for receptors on cells of the lower urogenital tract. Estriol increases urethral resting tone in females and is approved for estrogen-responsive urinary incontinence in ovariohysterectomized female dogs in the US, Australia, and the UK.
Estriol is rapidly absorbed after oral administration, and it is highly protein bound in plasma. Estrogens are widely distributed and are generally found in higher concentrations in sex hormone target organs. Estriol is conjugated in the liver and excreted via urine. The elimination half-life is 8–12 hours in dogs.
Adverse effects include anorexia, emesis, polydipsia, anxiety, aggression, lethargy, hypersalivation, swollen vulvae, estrous behavior, sexual attractiveness, and mammary hyperplasia. Estrogenic effects generally resolve with lowered dosage. Estriol should not be used with other estrogens. Polyuria and polydipsia, pregnancy, lactation, and age < 1 year are contraindications.
Alpha-Adrenergic Agonists for Treatment of Urinary Incontinence in Animals
Alpha-adrenergic agonists such as phenylpropanolamine (PPA), ephedrine, and phenylephrine act directly on smooth muscle receptors to increase urethral tone and maximal urethral closure pressure. Although often more clinically effective than diethylstilbestrol, these drugs have short-lived action that usually requires dosing every 8–12 hours.
Of this class of drugs, PPA is the most effective and has the fewest cardiovascular adverse effects. PPA is approved as a flavored tablet for urinary incontinence in dogs in the US.
Alpha-adrenergic agonist veterinary products approved for use in dogs are now available, including an extended-release tablet for once-daily administration. Ephedrine or phenylephrine may be tried; however, they are less efficacious than PPA. Adverse effects of alpha-adrenergic agonists include excitability, restlessness, hypertension, and anorexia.
Testosterone for Treatment of Urinary Incontinence in Animals
In male dogs, testosterone injections are used to treat urinary incontinence. However, testosterone is generally less effective in males than is estrogen in female dogs.
