Dog Incontinence Drugs: Medication Options Compared

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-09-20

Dog incontinence medication is most often prescribed to treat urethral sphincter mechanism incompetence, called USMI, a condition in which the muscle that holds urine inside the bladder no longer closes tightly enough. The two drugs veterinarians reach for first are phenylpropanolamine, an alpha-agonist that tightens the urethral sphincter, and diethylstilbestrol, known as DES, an estrogen used as a reserve option when phenylpropanolamine alone does not restore continence. This guide compares those two drugs with other options, explains which dogs they suit, and covers dosing, monitoring, side effects, and the point at which referral makes more sense than another dose adjustment.

This article is educational and is not a substitute for veterinary diagnosis or treatment.

At a Glance

Every entry in this table treats one specific problem, a weak urethral closure mechanism. None of them treats urgency, overflow, or incontinence caused by infection, stones, or spinal disease. That distinction decides whether a drug will help at all.

What USMI Is and Why It Causes Leaking

Urethral sphincter mechanism incompetence is the most common cause of acquired urinary incontinence in dogs [1]. The urethra has a ring of smooth and skeletal muscle that stays contracted between trips outside, holding urine in the bladder against the pressure building inside it. Incontinence happens when bladder pressure exceeds urethral pressure [2]. In USMI, the urethral closure pressure is too low, so urine escapes whenever abdominal pressure rises, such as when a dog lies down, stands up, or relaxes during sleep.

The condition is most common in neutered female dogs. In a study of 163 neutered bitches with USMI, affected dogs weighed more than continent control dogs, and heavier dogs carried a higher risk [3]. The same study found that the median time from neutering to the first episode of incontinence was 3.73 years, so many owners see the problem years after the spay rather than weeks [3]. Delaying neutering in bitches expected to reach more than 25 kg adult weight was associated with a lower hazard of developing USMI, while the timing of neuter did not change the hazard for bitches under 15 kg [3].

USMI is less common in male dogs. A retrospective review of 54 male cases found that the condition can be congenital or acquired, that neutering may play a part, and that larger breeds appear to be at greater risk [4]. Leaking in males tends to occur when intra-abdominal pressure rises, for example when the dog is recumbent, and the condition responds less reliably to medical therapy than it does in females [4]. That difference is one reason male dogs with suspected USMI are often referred earlier.

Congenital USMI exists as a separate presentation. A retrospective study of 19 bitches with congenital USMI found that all were started on phenylpropanolamine at 1.5 mg/kg orally once daily for at least a month, and continence scores after treatment did not differ significantly between bitches neutered before or after their first heat [5]. Congenital cases often appear in juvenile dogs, which changes the diagnostic path.

USMI Versus Urge and Overflow Incontinence

USMI is not the only reason a dog leaks, and the drugs in this article only address the USMI mechanism.

Urge incontinence comes from bladder irritation or overactivity. The bladder signals that it needs to empty even when it is not full, and the dog may leak while posturing, straining, or moving toward the door. Common triggers include urinary tract infection, bladder stones, and inflammation. A dog with urge incontinence usually has increased frequency, small volumes, and sometimes blood or straining. Phenylpropanolamine does not calm an overactive bladder. Treating the underlying infection or stone is the priority.

Overflow incontinence happens when the bladder cannot empty and urine backs up until it dribbles out. The bladder stays large and tense, and the dog may strain without producing a normal stream. Causes include urethral obstruction, a weak bladder muscle, and neurologic disease affecting the bladder. Alpha-agonists and estrogens can make overflow worse because they tighten the outlet further. A large, firm bladder on palpation is a reason to stop and reassess before starting any incontinence drug.

The practical rule is simple. USMI leaks when the dog is relaxed or recumbent, with normal urination otherwise. Urge leaks with urgency and frequency. Overflow leaks from a distended bladder. Only the first pattern fits the medications compared here.

First-Line Treatment: Phenylpropanolamine

Phenylpropanolamine is the first-line alpha-agonist for USMI in dogs. It is now available as an FDA-approved veterinary product, which means the formulation, dose, and label claims have been reviewed for use in dogs rather than adapted from human medicine.

How Phenylpropanolamine Works

Phenylpropanolamine stimulates alpha-1 adrenergic receptors on the smooth muscle of the urethra. Stimulation increases the tone of that muscle, raising urethral closure pressure so the outlet resists bladder pressure more effectively. Urethral pressure profilometry in bitches treated with phenylpropanolamine showed a significant increase in maximal urethral closure pressure after treatment compared with before treatment [6]. That is a direct measurement of the drug doing what it is supposed to do.

Dose and Administration

Dosing must come from the FDA-approved label or from Plumb's Veterinary Drug Handbook. A commonly cited regimen in the veterinary literature is 1.5 mg/kg orally once daily. In a retrospective study of nine bitches with USMI treated with a single daily dose of 1.5 mg/kg for at least one month, eight of nine achieved long-term continence, and the one non-responder went to surgery [6]. The same 1.5 mg/kg once-daily protocol was used in the congenital USMI study of 19 bitches [5]. In the large neutered-bitch population, phenylpropanolamine was prescribed in 75.5% of dogs, diethylstilbestrol in 21.5%, and both drugs together in 3.1% [3].

Follow the label or your veterinarian's instruction exactly. Do not split, crush, or compound the product unless directed. Give the dose at the same time each day to keep urethral tone steady around the clock. If a dose is missed, ask your veterinarian whether to give it when you remember or wait until the next scheduled dose.

What Phenylpropanolamine Does Not Cover

Phenylpropanolamine does not treat infection, stones, tumors, or neurologic disease. It does not calm bladder overactivity. It does not strengthen a bladder that cannot contract. If a dog has both USMI and a urinary tract infection, the infection still needs its own treatment, and the incontinence may not fully resolve until both problems are addressed.

Side Effects and Monitoring

Phenylpropanolamine raises blood pressure and heart rate in some patients, so blood pressure monitoring is part of responsible use. Restlessness, agitation, pacing, and changes in behavior are reasons to call your veterinarian. Loss of appetite, vomiting, and diarrhea can occur. Because the drug is a stimulant-type agent, dogs with heart disease, hypertension, hyperthyroidism, or glaucoma need a careful risk assessment before it is started.

Response should be reassessed at one to two weeks. If the dog is dry at that recheck, the dose may be continued as is. If leaking persists, your veterinarian may adjust the dose within label limits, add a second drug, or move toward a different strategy. Do not increase the dose on your own.

Reserve Estrogen: Diethylstilbestrol

Diethylstilbestrol is a synthetic estrogen used as a reserve option for USMI in dogs. It is compounded, which means it is prepared by a compounding pharmacy rather than sold as a finished FDA-approved veterinary product. Compounded drugs carry different quality and potency considerations than approved products, and the prescribing veterinarian is responsible for the decision to use one.

How DES Works

Estrogens increase the sensitivity of the urethral smooth muscle to alpha-adrenergic stimulation and can raise urethral closure pressure on their own. They also affect the vascularity and mucosal seal of the urethra. In practice, DES is often added when phenylpropanolamine alone leaves residual leaking, or used alone when an alpha-agonist is not tolerated.

Dose and Administration

Dosing must come from an approved reference such as Plumb's Veterinary Drug Handbook. DES is typically given orally on an intermittent schedule rather than daily, because the drug persists in the body for several days. Your veterinarian will set the dose and interval. Do not borrow a dose from another dog or from an older source, because compounding concentrations vary.

Bone Marrow Suppression Risk

Estrogens carry a risk of bone marrow suppression, which can be severe and sometimes irreversible. This is the main reason DES sits behind phenylpropanolamine in the treatment order and the main reason complete blood counts are part of monitoring. Any signs of lethargy, pale gums, bruising, nosebleeds, fever, or persistent infection while a dog is on DES warrant immediate veterinary contact.

Breeding Animals

Estrogens should not be used in breeding animals. DES and other estrogen products interfere with reproductive function, and the risk profile is not acceptable in dogs intended for breeding. If a dog is intact and intended to be bred, discuss the entire treatment plan with your veterinarian before any estrogen is given.

Other Estrogens

Estriol is another estrogen used in dogs, also compounded. It was one of the drugs in a case report of a dog with USMI that failed maximal doses of phenylpropanolamine and estriol before a different approach resolved the leaking [7]. That outcome does not mean estriol is ineffective in general, only that some dogs do not respond to standard medical management, which is the group that tends to be referred.

Other Medication Options

When phenylpropanolamine and estrogens do not produce acceptable control, several other drugs have been studied or used off-label. None of these is a first-line choice, and each has a specific rationale.

Methyltestosterone and Testosterone Analogues

Testosterone products have been used in castrated male dogs with USMI, and a retrospective study evaluated methyltestosterone in spayed female dogs. Ten spayed bitches with USMI received methyltestosterone at 0.32 to 1.27 mg/kg orally once daily to twice weekly. Nine of ten had good or excellent responses two to four weeks after starting, and the minimum effective dose was 0.32 mg/kg/day. No severe adverse effects occurred, though a mild, temporary increase in alanine aminotransferase was seen at doses of 1.0 and 1.1 mg/kg/day in two dogs. After dose reduction or withdrawal, two of eight dogs had recurrence, and restarting treatment clearly improved symptoms in both [8].

This is an off-label use. It is not a first-line option, and liver values need monitoring when it is used.

Leuprolide Acetate and GnRH Analogues

Leuprolide acetate is a long-acting GnRH analogue that suppresses gonadotropin release. In a study of 23 bitches with spay-related incontinence, phenylpropanolamine reduced incontinent episodes by 92% in the pre-trial period, while the GnRH analogue reduced episodes by 71% five weeks after treatment and placebo reduced them by 28%. By the end of the study, nine of twenty-two leuprolide-treated bitches responded completely and stayed continent for 70 to 575 days after treatment, and another ten had at least a 50% reduction in episode frequency. Treatment lowered plasma gonadotropin levels, but the degree of suppression did not correlate with the clinical response, and neither leuprolide nor placebo changed urethral closure pressure [9].

That last finding matters. The drug helped many dogs, but not by the mechanism originally proposed. It remains an off-label option rather than a first-line treatment.

GnRH Immunization

A GnRH vaccine has been tested as a way to lower circulating luteinizing hormone. In a study of 16 incontinent dogs already on phenylpropanolamine, 11 were immunized against GnRH and five received placebo. Ten of the eleven vaccinated dogs had side effects from vaccination, and two were withdrawn because of more severe reactions. Of the nine that completed the series, four remained continent after phenylpropanolamine was discontinued [10]. The side effect rate is high enough that this approach is not a routine recommendation.

When Drugs Are Not Enough

Some dogs do not reach continence on medication, or they reach it only at doses that cause unacceptable side effects. In the neutered-bitch population, phenylpropanolamine, DES, or both were the initial approach for nearly all dogs [3], but a subset fails. A prospective trial enrolled 15 dogs with USMI that had failed standard medical management and injected autologous skeletal muscle progenitor cells into the urethral submucosa. Median continence scores rose significantly at 3, 6, 12, and 24 months, and 14 of 15 dogs improved, though all but two still needed additional medication to reach continence [11]. That study defines the referral population: dogs that have failed standard drugs.

How the Drugs Compare

The comparison below focuses on the two drugs most owners will encounter and the alternatives that follow them.

Phenylpropanolamine is the drug to try first for most dogs with USMI. It has an approved veterinary product, a clear mechanism, measurable effects on urethral closure pressure, and a response that can be judged within one to two weeks [6]. DES is the reserve estrogen for dogs that need a second agent or cannot take an alpha-agonist, with bone marrow suppression as the reason it is not first [3]. The remaining drugs are for specific situations and are generally used under referral or after standard therapy fails.

The Decision Path

The flowchart below shows the main decision path from a leaking dog to the right next step.

flowchart TD
    A[Leaking dog] --> B[Rule out infection stones and neurologic causes]
    B --> C{Leak pattern fits USMI}
    C -->|No| D[Investigate urge or overflow cause]
    C -->|Yes| E[Start phenylpropanolamine]
    E --> F[Recheck at 1 to 2 weeks]
    F --> G{Continence achieved}
    G -->|Yes| H[Continue and monitor blood pressure]
    G -->|No| I[Add DES or adjust dose]
    I --> J[Recheck response and blood count]
    J --> K{Still leaking}
    K -->|Yes| L[Refer for advanced options]
    K -->|No| H

Giving Incontinence Medication Safely

A few practical rules reduce the chance of a bad outcome.

Give the drug exactly as prescribed, at the same time each day when the schedule is daily. Do not stop suddenly without asking, because continence can be lost and the reason for a change in control becomes harder to interpret. Do not double a dose to make up for a missed one unless your veterinarian tells you to.

Keep a simple log. Note the days your dog is dry, the days with leaking, and whether leaking happens when the dog is asleep, resting, excited, or moving. That pattern is the single most useful piece of information at the one to two week recheck, and it helps your veterinarian tell USMI from urge or overflow.

Watch for behavior changes on phenylpropanolamine. Restlessness, pacing, irritability, and difficulty settling are common enough that owners should know to expect them as a possibility. Report them rather than waiting for the next scheduled visit.

Watch for the signs of bone marrow suppression on any estrogen. Lethargy, pale gums, bruising, nosebleeds, and fever are emergencies.

Do not use estrogen products in a dog intended for breeding.

Keep all medications out of reach of other pets and children. Store compounded products according to the pharmacy label, since potency and stability depend on proper handling.

Questions to Ask Your Veterinarian

Before starting or changing a dog incontinence medication, these questions produce useful answers.

Which type of incontinence does my dog have, and what testing confirmed it? Ask whether a urinalysis and urine culture were done, since infection changes the plan.

Is the FDA-approved veterinary phenylpropanolamine product being prescribed, and what dose does the label specify for my dog's weight?

If DES or another estrogen is being added, what is the monitoring plan for blood counts, and how often will they be checked?

What response should I expect by the one to two week recheck, and what counts as failure?

Are there any heart, blood pressure, or eye conditions in my dog that make an alpha-agonist risky?

Is my dog intact or intended for breeding, and does that rule out any of these drugs?

What should I do if I see restlessness, agitation, or a behavior change?

At what point would you refer my dog to a specialist, and what would that referral involve?

Limitations and When to Contact a Veterinarian

This article describes medication classes and general monitoring principles. It cannot tell you the right drug or dose for an individual dog, because that depends on the diagnosis, the dog's weight, other medical conditions, and other medications. A veterinarian who has examined your dog should make those decisions.

Contact a veterinarian promptly if any of the following occur.

Your dog has not improved after one to two weeks on the prescribed dose. Persistent leaking at the recheck is the signal to reassess rather than wait.

Your dog develops restlessness, agitation, pacing, or a marked behavior change on phenylpropanolamine.

Your dog shows lethargy, pale gums, bruising, nosebleeds, or fever while taking an estrogen. These can indicate bone marrow suppression and need urgent evaluation.

Your dog strains to urinate, produces only a dribble, or has a large firm bladder. That pattern suggests overflow or obstruction, and incontinence drugs can make it worse.

Your dog has blood in the urine, increased frequency, or signs of pain when urinating. Infection or stones need their own treatment.

Your dog's leaking started suddenly, worsened quickly, or is accompanied by weakness, wobbling, or back pain. Neurologic causes and other conditions need to be ruled out.

Your dog is intact and intended for breeding. Estrogens should not be used in these animals.

Frequently Asked Questions

What is the most common dog incontinence medication?

Phenylpropanolamine is the most commonly prescribed drug for urethral sphincter mechanism incompetence in dogs, and it was prescribed in about three quarters of the neutered bitches in one large study [3].

Is phenylpropanolamine available as an approved veterinary product?

Yes. Phenylpropanolamine is now available as an FDA-approved veterinary product, which means it was reviewed for use in dogs rather than adapted from a human formulation.

Why is DES a reserve option rather than a first choice?

DES carries a risk of bone marrow suppression, so it is used after phenylpropanolamine or when an alpha-agonist is not suitable. Complete blood counts are part of monitoring.

Can estrogens be used in a dog I plan to breed?

No. Estrogens should not be used in breeding animals because of their reproductive effects and overall risk profile.

How soon should I expect improvement?

Response is typically judged at a one to two week recheck. Some dogs improve within days, and others need a dose adjustment or a second drug before continence is reached.

What should I monitor at home?

Track dry days, leaking episodes, and whether leaking happens at rest or during activity. Also watch for restlessness, behavior changes, lethargy, bruising, or bleeding, and report any of these.

What if my dog does not respond to medication?

Dogs that fail standard medical management are candidates for referral. Advanced options studied in this group include urethral bulking agents and cell-based injections, and some dogs still need medication afterward [11][12].

Can incontinence in dogs be cured rather than managed?

Some dogs become continent on medication and stay that way, while others need ongoing treatment. Response varies by cause, sex, and whether the dog has other conditions, and male dogs respond less reliably to medical therapy than females [4].

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Sources

1. Urethral Sphincter Mechanism Incompetence in Dogs: An Update.
2. Surgical views: Surgical treatment of urethral sphincter mechanism incompetence in dogs.
3. Urethral Sphincter Mechanism Incompetence in 163 Neutered Female Dogs: Diagnosis, Treatment, and Relationship of Weight and Age at Neuter to Development of Disease.
4. Urethral sphincter mechanism incompetence in male dogs: a retrospective analysis of 54 cases.
5. Congenital urethral sphincter mechanism incompetence: observational clinical findings and treatment outcomes-a small retrospective study in 19 bitches.
6. Clinical evaluation of a single daily dose of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch.
7. Treatment of lower back pain to resolve symptoms of canine urethral sphincter mechanism incontinence.
8. Clinical assessment of testosterone analogues for urethral sphincter mechanism incompetence in ten spayed female dogs.
9. Effect of a long acting GnRH analogue or placebo on plasma LH/FSH, urethral pressure profiles and clinical signs of urinary incontinence due to Sphincter mechanism incompetence in bitches.
10. Gonadotropin-releasing hormone immunization for the treatment of urethral sphincter mechanism incompetence in ovariectomized bitches.
11. The use of autologous skeletal muscle progenitor cells for adjunctive treatment of presumptive urethral sphincter mechanism incompetence in female dogs.
12. Evaluation of cross-linked gelatin as a bulking agent for the management of urinary sphincter mechanism incompetence in female dogs.