Diethylstilbestrol for Dogs: When and How it is Used

Diethylstilbestrol (DES) is a synthetic estrogen used to treat urine leaking in spayed female dogs. It's given once a day for a few days, then about once a week.¹ It's also become hard to get. The licensed DES tablet in Canada has been discontinued, and we've switched our patients to estriol, a natural estrogen that works the same way. In the US, DES is available only from compounding pharmacies.²

What is diethylstilbestrol (DES)?

DES is a man-made estrogen that vets use for urethral sphincter mechanism incompetence (USMI), a weakness in the muscle that keeps the urethra closed. It's the most common cause of leaking in dogs whose bladder and nerves are otherwise normal, and many people call it spay incontinence.¹

USMI is usually linked to the drop in sex hormones after spaying. It affects between 3% and 20% of spayed females and is much less common in males.¹

Is diethylstilbestrol still available for dogs?

Not in Canada. The licensed DES tablet, sold as Stilbestrol, has been discontinued, so we now use estriol instead. In our experience it controls leaking well. The catch is that it has to be given every day or every second day, where many dogs on DES needed only one dose a week.

In the US, DES is still prescribed, but only as a compounded medication. There's no FDA-approved version, while PPA and estriol are both approved for dogs.² Some compounding pharmacies have stopped making DES, so check with yours before the supply runs low.

If you can't get a refill, contact your vet before the last dose so the switch to estriol or PPA happens without a long gap.

How does diethylstilbestrol (DES) work in dogs?

DES makes the urethral sphincter more responsive to norepinephrine, the nerve signal that tells the muscle to tighten. A tighter sphincter holds urine in the bladder.^1,4

Dogs with USMI most often leak while lying down or resting. As the bladder fills, the pressure inside it overcomes the weakened sphincter.¹ Many are dry during the day and leave a wet patch where they sleep.

DES also lasts a long time in the body. It's absorbed quickly and peaks in the blood about an hour after a dose. The liver and gut then recycle it, which stretches its half-life in dogs to about 24 hours.⁴ Estriol is short-acting,⁶ which is why it has to be given more often.

How well does diethylstilbestrol work in dogs?

In a study of 31 spayed dogs treated with DES, 20 stopped leaking completely, 7 improved and 4 didn't respond.³ It's a small study from 1987, and no trial has compared estrogen head to head with PPA.¹

Estriol has been studied more thoroughly. In a placebo-controlled trial of 206 dogs, treatment succeeded in 66% of dogs on estriol after 14 days, compared with 37% on placebo.⁷ In another study of 129 dogs, 83% became continent or improved.⁶ PPA is often more effective than DES, though it needs two or three doses a day.^1,4

What to check before starting DES

DES only helps one kind of urinary incontinence in dogs, so we confirm the cause first. Every dog that leaks urine should have a urinalysis and urine culture to check for a bladder infection.¹

Drinking and urinating more than usual also makes leaking worse.¹ If your dog is thirstier than usual, find out why. It could be a medication such as prednisone, kidney disease, or a less common hormone problem such as diabetes insipidus.

Leaking is also different from trouble emptying the bladder. A dog that strains to pee or dribbles after she's finished may have a voiding problem such as reflex dyssynergia, which needs a different treatment.¹ A young dog that has leaked constantly since puppyhood is more likely to have an ectopic ureter, a birth defect where a ureter bypasses the sphincter.¹

Diethylstilbestrol dosage for dogs

The usual starting dose is 0.1 to 1 mg per dog by mouth, once a day for 3 to 5 days. Once the leaking stops, the dose drops to once a week, or less often if she stays dry.¹ It's set per dog rather than per kilogram, scaled to her size and adjusted to how she responds.⁵

The aim is the lowest dose that keeps her dry, because estrogen side effects often depend on the dose.¹ Some dogs can take breaks from DES and restart it if the leaking returns.⁵

Because it's compounded, DES comes as a capsule, tablet or liquid made for your dog. It can be given with or without food, and giving it with a meal helps if it upsets her stomach. If you miss a dose, don't double the next one. Carry on with the usual schedule.

What are the side effects of diethylstilbestrol in dogs?

Most side effects are mild and ease when the dose is lowered. The common ones are:^1,5

• Swelling of the vulva or mammary glands
• Attracting male dogs, though only intact males take an interest
• Behaviour changes
• Thinning hair, reported in dogs treated for several months, which grows back once the drug is reduced or stopped

Bone marrow suppression is the serious one. It usually shows up first as a low platelet count and can progress to aplastic anemia, which can be fatal.⁴ It's rare at the doses used for incontinence and has mostly been reported with high doses of DES or with a different estrogen, estradiol cypionate.¹ If you see pale gums, bruising or bleeding, stop DES and call your vet the same day.

Estrogen also affects the uterus. In females that haven't been spayed, it can cause cystic endometrial hyperplasia and pyometra, a uterine infection.⁴ That's one reason DES is reserved for spayed dogs.

If your dog starts drinking more while on DES, have her checked. Extra drinking makes leaking worse, and it can point to another illness.¹

Precautions for dogs and people

DES isn't used in pregnant or nursing dogs or in dogs with estrogen-sensitive cancers. Specialists also advise against estrogen in young females that haven't had a heat yet, because of the risk of an enlarged uterus or pyometra.¹ Male dogs with USMI start on PPA instead.¹

DES is also a known risk to people. Between 1940 and 1971 it was prescribed to pregnant women, and their daughters turned out to have about 40 times the usual risk of a rare cancer of the vagina and cervix.⁸ Anyone who is pregnant, trying to conceive or breastfeeding shouldn't handle it. Everyone else should wear gloves and wash their hands after giving a dose.

Estriol carries a milder version of the same warning. Women who are pregnant, could become pregnant or are breastfeeding should take care handling it, and everyone should wash their hands afterwards.⁷

Alternatives to DES: estriol and PPA

Both are approved for dogs in the US, and both need more frequent dosing than DES.^1,2,7

PPA is the usual first choice. All eight internal medicine specialists on the 2024 ACVIM consensus panel start with it, and when it fails, six of the eight move to estriol and two to DES.¹ PPA tightens the sphincter by stimulating its nerve receptors directly, so it works in males as well as females. It can raise blood pressure, so your vet should measure it before starting and recheck it periodically. Give it at least 28 days before deciding whether it's working.¹

Estriol is a natural estrogen approved for spayed female dogs, and it acts on the sphincter the same way DES does.^1,7 The label dose is 2 mg once a day for at least 14 days. After that it's stepped down, no faster than once a week, to the lowest dose that keeps her dry, which can be as little as 0.5 mg every second day.⁷ In a 6-week trial, blood tests on 114 dogs taking estriol found no abnormalities.⁶

An estrogen and PPA can be given together to a dog that doesn't respond to either one alone. One study found no added benefit, but some dogs do better on the combination or need less of each drug.¹

If medication doesn't control the leaking, a specialist can inject a bulking agent into the urethra or place an artificial urethral sphincter. Bulking agents make over 80% of dogs continent, but the leaking returns within a year in many. The artificial sphincter has the best long-term results.¹

If your dog is leaking urine or running low on DES, call us at (519) 896-0532 to book an exam.