Uterine Adenocarcinoma in Rabbits

TL;DR. Uterine adenocarcinoma is a highly common and malignant uterine cancer in unspayed female rabbits over three years old, but it is entirely preventable through early spaying.

Unlike many other mammals, female rabbits possess a duplex uterus with two separate uterine horns and cervices.

What is it?

Uterine adenocarcinoma (specifically endometrial adenocarcinoma) is the most common tumor diagnosed in female rabbits. It is a slow-growing but highly malignant cancer that originates in the endometrium, which is the inner glandular lining of the rabbit's uterus. Because the disease progresses gradually, it often goes unnoticed by owners in its early stages. However, as the tumor grows, it eventually invades the deeper layers of the uterine wall and can spread (metastasize) to other vital organs, most commonly the lungs and the liver.

To understand this disease, it helps to understand the unique anatomy of the female rabbit's reproductive tract. Unlike dogs, cats, and humans, female rabbits have a "duplex" uterus. This means they possess two entirely separate uterine horns, each with its own cervix opening into a single vagina. Uterine adenocarcinoma can develop in one or both of these uterine horns. Over time, the tumor causes the uterine tissue to become thickened, cystic, and highly prone to bleeding.

This cancer is a significant concern for rabbit owners because of its remarkably high prevalence. Veterinary studies indicate that up to 50% to 80% of intact (unspayed) female rabbits will develop uterine adenocarcinoma by the time they reach three to four years of age. Understanding the early signs of this disease and the critical importance of preventive care is essential for ensuring your rabbit lives a long, healthy life.

Causes & risk factors

The primary risk factor for developing uterine adenocarcinoma is leaving a female rabbit intact (unspayed) as she ages. Age is the single most significant variable; while the disease is rare in rabbits under two years of age, the risk increases dramatically once a rabbit passes her third birthday.

The underlying cause of the tumor is closely linked to chronic hormonal stimulation. Rabbits are induced ovulators, meaning they do not experience a regular, cyclic estrous cycle like many other mammals. Instead, they remain in a state of persistent estrogen dominance unless they are bred. Over several years, this constant hormonal stimulation causes progressive, abnormal changes in the endometrium. This process typically begins as cystic endometrial hyperplasia (a benign thickening of the uterine lining), which gradually transitions into cellular changes, localized carcinoma, and eventually invasive, metastatic adenocarcinoma.

While any unspayed female rabbit is at high risk, certain breed predispositions have been identified. Retrospective veterinary studies suggest that the Dutch Rabbit and the Havana breed may have a higher genetic susceptibility to developing this tumor compared to other breeds. However, no intact female rabbit of any breed is considered safe from this disease as she ages.

Signs to watch for

In its earliest stages, uterine adenocarcinoma is virtually silent, showing no outward physical signs. As the tumor grows and begins to alter the uterine tissue, several clinical signs will emerge. Owners should monitor their rabbits closely for the following symptoms:

• Hematuria or bloody vaginal discharge (Cardinal): This is the most common and classic sign of uterine cancer. Owners often notice blood dripping from the vulva or mixed with the rabbit's urine. It is important to distinguish this from normal rabbit urine, which can naturally range from yellow to dark orange or red due to dietary pigments (porphyrins). True blood from a uterine tumor often appears as distinct red spots, streaks, or blood clots on the cage floor or bedding, and the bleeding is typically intermittent.
• Pale mucous membranes (Common): Chronic, slow bleeding from the uterine tumor over weeks or months leads to progressive iron-deficiency anemia. You may notice that your rabbit's gums, inside of the lips, and the tissue around the eyes appear pale pink or white instead of a healthy, vibrant pink.
• Abdominal mass or uterine enlargement (Common): As the tumor grows, the uterus becomes physically enlarged and firm. A veterinarian can often feel this abnormal mass during a routine physical examination of the abdomen.
• Lethargy (Occasional): Anemic or painful rabbits will often show a decrease in their normal activity levels, preferring to sit quietly in their enclosure rather than explore or play.
• Anorexia and weight loss (Occasional): A gradual decline in appetite and subsequent weight loss can occur as the disease progresses. In rabbits, any reduction in food intake is a major concern, as it can quickly trigger a secondary, life-threatening condition called gastrointestinal (GI) stasis.
• Dyspnea (Occasional): Difficulty breathing or rapid, shallow breathing is a late-stage symptom. This occurs when the cancer has metastasized to the lungs, replacing functional lung tissue with tumor nodules. Any sign of labored breathing in a rabbit is a critical veterinary emergency.

Lethargy and a hunched posture can be subtle signs of pain or anemia caused by uterine tumors in rabbits.

How vets diagnose it

Diagnosing uterine adenocarcinoma requires a systematic veterinary evaluation. Because rabbits are prey animals, they instinctively hide signs of illness until they are severely compromised, making professional diagnostic testing essential.

Your vet will begin with a thorough physical examination, including careful palpation of your rabbit's abdomen. An enlarged, firm, or nodular uterus is highly suspicious in an intact female. To confirm the diagnosis and assess whether the cancer has spread, your vet will recommend several key diagnostic tests:

• Abdominal Ultrasonography: This is an invaluable, non-invasive imaging tool. Ultrasound allows the veterinarian to visualize the internal structure of the uterus, measure the thickness of the uterine wall, and identify solid tumor masses or fluid-filled cavities within the uterine horns.
• Thoracic and Abdominal Radiography (X-rays): Before pursuing surgery, your vet will perform X-rays. Abdominal X-rays help evaluate the size of the uterus and check for abdominal fluid or enlarged lymph nodes. Thoracic (chest) X-rays are absolutely critical to screen for pulmonary metastasis. If the cancer has spread to the lungs, it typically appears on X-rays as multiple round, soft-tissue density nodules (often referred to as "cannonball" lesions). Detecting metastasis is vital, as it drastically changes the treatment plan and prognosis.
• Histopathology of the Uterus (Gold Standard): While imaging can strongly suggest uterine adenocarcinoma, a definitive diagnosis can only be achieved by submitting the surgically removed uterine tissue to a veterinary pathologist. The pathologist will examine the tissue under a microscope to identify the characteristic malignant epithelial cells of endometrial adenocarcinoma and confirm whether the entire tumor was successfully removed.

Abdominal ultrasonography is a key diagnostic tool used to visualize uterine thickening and identify tumor masses.

Treatment options

Treating uterine adenocarcinoma depends heavily on whether the cancer has metastasized to other parts of the body.

Surgical Therapy (Primary Cure)

For rabbits with localized disease (where the cancer is strictly confined to the uterus), the primary and most effective treatment is an ovariohysterectomy (spay). During this surgical procedure, the veterinarian removes both ovaries and the entire duplex uterus, including both cervices.

Performing surgery on an exotic pet requires specialized veterinary care. Your vet will use tailored anesthetic protocols, provide active warming to maintain the rabbit's body temperature, and administer intravenous fluids to support blood pressure. If the tumor is removed entirely before it has metastasized, the surgery is curative.

Medical Management & Supportive Care

If the rabbit is undergoing surgery, or if the cancer has already spread and the owner is pursuing palliative care to keep the rabbit comfortable, medical management is essential. This typically involves:

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Medications such as meloxicam are commonly prescribed. These drugs help manage chronic pain and reduce inflammation associated with the tumor or post-operative recovery. Rabbits metabolize NSAIDs rapidly and generally require higher relative doses than dogs or cats to achieve effective pain relief.
• Opiate Partial Agonists: For moderate to severe pain, particularly in the immediate post-operative period, medications like buprenorphine are utilized. Keeping a rabbit pain-free is vital because pain can cause them to stop eating, which quickly leads to fatal gastrointestinal stasis.
• Nutritional Support: If a rabbit's appetite is diminished due to the disease or recovery from surgery, aggressive supportive care is required. This includes syringe-feeding specialized high-fiber recovery formulas and administering gastrointestinal prokinetic medications to keep the digestive tract moving.

Prognosis

The long-term outlook for a rabbit with uterine adenocarcinoma is highly variable and depends entirely on the timing of the diagnosis:

• Excellent Prognosis: If the disease is detected early, before the tumor has metastasized, and an ovariohysterectomy is successfully performed, the prognosis is excellent. The surgery is curative, and the rabbit can go on to live a normal, healthy lifespan.
• Guarded to Poor Prognosis: If thoracic radiographs or abdominal ultrasound reveal that pulmonary or hepatic (liver) metastasis has already taken place, the prognosis is poor. In these cases, surgery is no longer curative, and treatment shifts to palliative care. The focus becomes managing pain with NSAIDs and opioids, supporting nutrition, and maintaining the rabbit's quality of life for as long as possible. Survival times for rabbits with metastatic disease are typically limited to several weeks or months.

Prevention

Uterine adenocarcinoma is one of the few highly common, malignant cancers in veterinary medicine that is 100% preventable.

The absolute gold standard for prevention is routine ovariohysterectomy (spaying) of all female rabbits at a young age. Most exotic veterinarians recommend spaying female rabbits between 4 and 6 months of age, once they reach sexual maturity. Spaying at this stage is a safe, routine procedure that completely eliminates the risk of uterine adenocarcinoma, as the target tissue is removed before abnormal cellular changes can ever begin.

In addition to preventing cancer, spaying your rabbit offers several other significant health and behavioral benefits:

• Prevents other life-threatening uterine conditions, such as pyometra (a severe uterine infection), hydrometra (fluid accumulation in the uterus), and uterine torsion.
• Eliminates the risk of unwanted pregnancies.
• Significantly reduces or eliminates hormone-driven behaviors, such as territorial aggression, urine spraying, and destructive nesting behaviors.

If you adopt an older, unspayed female rabbit, it is highly recommended to schedule a veterinary consultation to discuss a preventative spay, even if she is over two years old, provided she is deemed a safe anesthetic candidate after a thorough pre-operative screening.

When to call your vet

Because rabbits hide illness so effectively, you must act quickly if you notice any changes in their behavior or physical appearance.

Contact your veterinarian immediately if you observe any of the following emergency red flags:

• Active bleeding or large blood clots from the vulva
• Difficulty breathing, rapid breathing, or open-mouth breathing
• Complete loss of appetite (anorexia) lasting more than 12 hours
• Extreme lethargy, weakness, or inability to stand

Schedule an urgent appointment if you notice more gradual changes, such as a slowly declining appetite, progressive weight loss, pale gums, or intermittent pink-tinged urine.

For specific breeds

If you own a Dutch Rabbit or a Havana, you should be extra vigilant. While all intact female rabbits face an incredibly high risk of developing uterine cancer as they age, these specific breeds have a suspected genetic predisposition that may make them even more vulnerable.

If you have a young female Dutch or Havana rabbit, prioritizing a preventative spay between 4 and 6 months of age is the single most important healthcare decision you can make for her. If you own an older, intact female of these breeds, discuss diagnostic screening (such as abdominal ultrasound) with your veterinarian as soon as possible to check for early signs of uterine changes.

Sources

Guidance on the diagnosis, treatment, and prevention of uterine adenocarcinoma in rabbits is derived from standard-of-care veterinary knowledge and established reference texts in exotic animal medicine, including:

• Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery (Section on Rabbit Reproductive Diseases, pp. 210-218)
• BSAVA Manual of Rabbit Medicine (Chapter on Oncology and Reproductive Tract Diseases, pp. 145-152)