Brand Name: Incurin

Available as 1 mg tablets

Background

Estrogens are potent female hormones produced naturally by the ovary and needed for the normal development of the female reproductive tract as well as for normal female fertility. Synthetic estrogens have, in the past, found assorted medical and industrial uses. In the 1960s, researchers found that sphincter-related incontinence in post-menopausal women was alleviated by giving estrogens. Soon, the sphincter incontinence that is common in spayed female dogs was also being treated effectively with estrogen in the form of diethylstilbestrol (DES).

DES was originally used commercially as a growth promoting agent in livestock, as a human medication to help maintain pregnancy and to treat prostate cancer in humans decades ago, but was removed from these uses due to human safety issues. As the uses of DES dwindled to a few veterinary uses, its manufacturer found it unprofitable to continue its production and DES went off the market in the late 1990s.

DES continues to be available to patients through compounding pharmacies; however, estriol has received FDA approval and represents another way to use estrogens for sphincter incontinence in female dogs.

Both phenylpropanolamine and estriol are FDA-approved for canine incontinence. This article reviews estriol, which has been available to dogs in other countries for at least a decade longer than in the U.S. 

How this Medication is Used

Several protocols have been published and tested regarding the initial use of estriol for canine incontinence. They all come down to this: begin at a daily dose for approximately two weeks and, if it works, taper to a lower dose each week until the minimum effective dose for the individual dog has been determined. At least seven days at each dose adjustment are needed to assess the dose. Approximately 90 percent of dogs will either be completely continent or significantly improved with this medication. The maximum dose of this medication is felt to be 2 mg daily, but if incontinence is not resolved after two weeks of this dosage, then the diagnosis and treatment plan should be reconsidered. 

Never give more than 2 mg of estriol in a 24-hour period. If a dose is accidentally skipped and a day has not passed, the dose can simply be given when it is remembered. If a day is accidentally skipped, simply give the next dose as scheduled. Do not double up on doses.  

Estriol can be given with or without food.

Side Effects

The most common side effects of estriol were reduced appetite and vomiting. Appetite reduction was experienced in about 13 percent of dogs, and vomiting in about 10 percent. Increased thirst is also a reported side effect. Reducing the dose generally controls these issues. 

Effects related to female hormones are also seen, but only rarely: swollen vulva (4% of patients), sexual attractiveness (3.5%), breast enlargement, and behavior consistent with being in heat (1%).

Estriol is a short-acting female hormone that affords extra safety compared with other female hormones. Bone marrow suppression has been an issue with other estrogens, but this has not been reported with short-acting estrogens, such as estriol, at the very low doses needed to correct urinary incontinence.

Interactions with Other Drugs

The use of this medication may alter thyroid hormone levels.

This medication should not be used in combination with other estrogens, or there may be an increased risk for hormone-related side effects, the worst of which is bone marrow suppression.

Concurrent use of phenobarbital may interfere with the effectiveness of estriol by enhancing its removal from the body.

Concurrent use of ketoconazole may elevate blood levels of estriol by interfering with its removal from the body. Similar issues occur with the use of cimetidine (an antacid) and macrolide-class antibiotics (such as clarithromycin or erythromycin).

Concurrent use of estriol and cyclosporine (an immunomodulator) may increase cyclosporine blood levels.

Thyroid supplements may not work as well in the presence of estriol.

Ursodiol may not work as well in the presence of estriol.

Concerns and Cautions

Two tablets daily is felt to be the maximum dose for any dog, and if this is not adequate to control incontinence, another therapy or further diagnostics should be elected.

Estriol should not be used in male dogs, pregnant or lactating dogs, or dogs under the age of one year.

Pregnant or breastfeeding women should wash their hands after handling estriol.

Estriol should be used with caution in patients with liver disease.

Estriol should be stored at room temperature in blister packs, protected from light.