Depo-Promone is one of the most effective injectable heat suppressants available in veterinary medicine — a single subcutaneous injection can prevent or suppress oestrus in female dogs for up to 6 months and in cats for 4–6 months. But it is also one of the most misused products in small animal reproductive management, with serious complications that arise almost entirely from incorrect timing of administration or inappropriate patient selection.
This guide covers everything owners and vets need to know: how it works, the critical timing rules, exact doses, what risks to watch for, and when alternative options (spaying, GnRH implants, oral progestogens) are a better choice.
What Is Depo-Promone?
Depo-Promone is an injectable suspension manufactured by Pfizer Animal Health, containing medroxyprogesterone acetate (MPA) 50mg per ml. Medroxyprogesterone acetate is a long-acting synthetic progestogen — a progesterone analogue — that suppresses the hormonal cascade driving oestrus in female dogs and cats. It is available in 3ml and 5ml vials.
How Does Depo-Promone Suppress Heat?
MPA works at three levels of the reproductive system simultaneously:
- Hypothalamic-pituitary level: MPA blocks GnRH release from the hypothalamus, which in turn prevents the pituitary gland from secreting FSH and LH. Without FSH and LH, follicle maturation stops and ovulation cannot occur.
- Tubal transport: Even if follicle activity were to occur, MPA alters fallopian tube contractility, disrupting oocyte transport and preventing fertilisation.
- Uterine environment: MPA modifies the endometrial lining, making successful implantation of a fertilised egg impossible.
Because MPA is a depot formulation (suspended in an aqueous carrier designed for slow absorption), a single injection provides months of sustained suppression rather than requiring daily dosing.
The Most Important Rule: Timing
This is where most problems with Depo-Promone occur. MPA must only be given during anoestrus — the resting phase of the reproductive cycle that occurs between heats. Specifically, it should be given in the second half of anoestrus, approximately 3 months after the end of the last heat.
Administering Depo-Promone during or just before a heat cycle (during pro-oestrus, oestrus, or metoestrus) massively increases the risk of endometrial hyperplasia, pyometra, and mammary disease. This is not a minor consideration — pyometra is a life-threatening emergency requiring emergency spaying.
How to Know Your Animal Is in Anoestrus
- The animal shows no signs of heat (no vulval swelling, no discharge, no attractiveness to males, no behavioural changes)
- At least 3 months have passed since the last heat cycle ended
- If uncertain, a veterinarian can perform vaginal cytology or measure serum progesterone to confirm anoestrus before injection
Never inject if there is any doubt about the current cycle stage.
Dosage Guide
Administer by subcutaneous injection only. Do not give intravenously. Shake well before use. Choose an inconspicuous injection site to minimise the visibility of any hair discolouration that may occur.
| Patient | Volume | MPA Dose | Repeat Interval |
|---|---|---|---|
| Standard bitches | 1.0–1.5 ml | 50–75 mg | Every 6 months (during anoestrus) |
| Small bitches (<10 kg) | 0.5 ml | 25 mg | Every 6 months (during anoestrus) |
| Queens (cats) | 1.0 ml | 50 mg | Every 4–6 months (during anoestrus) |
Two Different Uses
To prevent the next heat (one-off): Give a single injection 15–21 days before the expected date of the next heat. The animal will skip that heat cycle. Normal cycling will eventually resume.
For long-term (permanent) heat suppression: Give injections on the schedule above, renewed at each interval during anoestrus. This maintains continuous suppression as long as treatment continues.
Which Animals Should NOT Receive Depo-Promone?
Depo-Promone has a significant contraindication list that must be worked through before every injection:
- Animals currently in pro-oestrus, oestrus, or metoestrus
- Prepubescent animals that have not yet had their first heat
- Animals intended for breeding
- Pregnant animals
- Animals with existing or suspected mammary tumours
- Diabetic animals (MPA has an anti-insulin effect)
- Animals with uterine disease: pyometra, endometritis, endometrial hyperplasia
- Animals with a history of irregular heat cycles, nymphomania, or false pregnancy
- Animals with prolonged or unusual vaginal discharge
- Greyhounds (continuous treatment not recommended in this breed)
Side Effects — What Owners Need to Know
MPA is a potent hormone with a recognised and significant side effect profile. These risks are real and increase with repeated use:
Uterine Disease
Endometrial hyperplasia and pyometra (life-threatening uterine infection requiring emergency surgery) are among the most serious adverse events. They can occur after even a single injection, but risk increases substantially with repeated treatments. This is why many veterinary guidelines now recommend spaying over long-term MPA use in otherwise healthy animals.
Mammary Complications
MPA stimulates mammary gland development. Mammary hypertrophy and mammary tumours have been reported. This is particularly concerning given that mammary tumours are already the most common neoplasm in intact female dogs.
Diabetes Mellitus
MPA has a significant anti-insulin effect. In animals with pre-existing insulin resistance or subclinical diabetes, MPA can precipitate overt diabetes. In known diabetic animals, it is absolutely contraindicated.
Behavioural and Metabolic Changes
Polyphagia (increased appetite), weight gain, lethargy, and personality changes including aggression or apathy have been reported.
Growth Hormone Stimulation
MPA stimulates growth hormone secretion from mammary gland tissue. This can lead to acromegaly-like changes in some dogs (enlarged paws, coarsened facial features), as well as insulin resistance.
Injection Site Reaction
A localised patch of hair discolouration or permanent alopecia can develop at the SC injection site. Always choose an inconspicuous location (lateral neck, flank) to minimise cosmetic impact.
Return of Fertility — What Happens When You Stop
If Depo-Promone injections are discontinued, the heat cycle will eventually return — but the timeline is unpredictable. Most animals return to oestrus within 6 months of the last injection, but delays of up to 2 years or longer are possible. Owners must be clearly informed of this before starting treatment, particularly if the animal may be needed for breeding later.
After stopping treatment, wait for at least two normal heat cycles before attempting breeding to allow the uterus to fully recover to a normal pre-injection state.
Drug Interactions
- Corticosteroids: Combination with corticosteroids can worsen or precipitate diabetes mellitus. Avoid concurrent use where possible.
- Insulin: Absolute contraindication — do not use Depo-Promone in any animal receiving insulin therapy. MPA makes glycaemic control essentially impossible.
Depo-Promone vs Other Heat Suppression Options
Depo-Promone is not the only option for managing oestrus. Understanding the alternatives helps in choosing the right approach for each animal:
| Method | Duration | Reversible? | Key Advantage | Key Risk |
|---|---|---|---|---|
| Depo-Promone (MPA injection) | 6 months (dogs) / 4–6 months (cats) | Yes | Single injection, long effect | Pyometra, mammary tumours, diabetes |
| Megestrol tablets (Nonovulin) | Requires daily dosing | Yes — easily stopped | Dose easily adjusted | Similar risks to MPA injection |
| GnRH implant (Suprelorin) | 6 or 12 months | Yes | No uterine or mammary risks | Cost, availability, initial flare |
| Ovariohysterectomy (spay) | Permanent | No | Eliminates pyometra and reduces mammary tumour risk | One-time anaesthetic/surgical risk |
For most healthy dogs and cats where long-term contraception is desired, spaying or GnRH implants have more favourable safety profiles than repeated MPA injections. Depo-Promone is most appropriate for animals where surgery is genuinely higher risk than hormonal treatment, or for short-term, one-off heat prevention.
Where to Buy Depo-Promone
You can order Depo-Promone 3ml and Depo-Promone 5ml from PetShopBoss.com with free worldwide shipping. Related products: Nonovulin Anti-Estrus Tablets for Dogs & Cats | Alizin Injection (Aglepristone) for Unwanted Pregnancy & Pyometra in Dogs

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