Pseudopregnancy (Pseudocyesis)

Pseudopregnancy, also known as pseudocyesis or false pregnancy, is a clinical syndrome in non-pregnant female dogs (and occasionally cats) characterized by behavioral and physical signs of pregnancy and lactation, occurring typically 6 to 12 weeks after estrus. It results from the normal luteal phase of the estrous cycle, where the corpus luteum secretes progesterone for approximately 60 to 70 days, followed by a decline in progesterone and a rise in prolactin. This hormonal shift triggers mammary gland development, milk production, and maternal behaviors such as nesting, mothering of inanimate objects, and sometimes aggression. The condition is considered a normal physiological phenomenon in the bitch, but it can become pathological when signs are severe or prolonged. In cats, pseudopregnancy is rare and usually occurs after an infertile mating or induced ovulation without conception. The syndrome is classified as overt (clinical signs) or covert (hormonal changes without clinical signs). It is important to differentiate pseudopregnancy from true pregnancy, pyometra, and other reproductive disorders.

The primary etiology of pseudopregnancy is the normal endocrine events of the canine estrous cycle. After ovulation, the corpus luteum produces progesterone, which maintains the uterine environment for a potential pregnancy. If pregnancy does not occur, the corpus luteum regresses, and progesterone levels decline. This decline, particularly the rapid drop at the end of the luteal phase, triggers an increase in prolactin secretion from the anterior pituitary. Prolactin is the key hormone responsible for mammary development and lactation. In some bitches, the prolactin response is exaggerated, leading to clinical signs. The exact cause of this exaggerated response is not fully understood but may involve individual variation in hypothalamic-pituitary sensitivity, altered dopamine tone, or increased prolactin receptor sensitivity. Iatrogenic causes include administration of progestins (e.g., medroxyprogesterone acetate) or withdrawal of exogenous progesterone, which can mimic the hormonal changes. In cats, pseudopregnancy occurs after ovulation without fertilization, as the corpus luteum persists for about 30 to 40 days, and prolactin levels rise, but clinical signs are usually mild. Genetic factors may play a role, as certain breeds (e.g., Beagles, Dachshunds, and some toy breeds) appear predisposed. No infectious agents are directly implicated, but secondary mastitis can occur due to milk stasis.

Pseudopregnancy is a common condition in intact female dogs, with an estimated incidence of 50% to 75% of bitches showing some degree of clinical signs after estrus, though severe signs requiring treatment occur in about 5% to 10% of cases. It can occur in any breed, but some breeds such as Beagles, Dachshunds, and Poodles are reported to have a higher incidence. It is more common in nulliparous bitches and those that have not been bred, but it can also occur in previously pregnant bitches. Age of onset is typically after the first estrous cycle, and it recurs with each cycle in susceptible individuals. In cats, pseudopregnancy is rare and usually occurs in queens that have been bred with an infertile male or that have undergone an induced ovulation without conception. It is more common in older queens. There is no sex predilection in males, as the condition is exclusive to females. Breeding status is a significant factor: bitches that are not bred are more likely to develop clinical signs than those that are bred, possibly due to the lack of pregnancy-associated hormonal modulation. Environmental factors such as stress or the presence of other pregnant or lactating females may exacerbate signs.

The pathophysiology of pseudopregnancy is rooted in the endocrine dynamics of the canine estrous cycle. After ovulation, the corpus luteum secretes progesterone, which remains elevated for 60 to 70 days. In a non-pregnant bitch, the corpus luteum regresses spontaneously, and progesterone levels fall. This decline is not gradual but often occurs as a rapid drop, particularly after day 40. The sudden decrease in progesterone removes its negative feedback on prolactin secretion, leading to a surge in prolactin from the anterior pituitary. Prolactin is luteotropic in the dog and also stimulates mammary gland development and lactation. The elevated prolactin levels cause proliferation of mammary alveolar epithelium, secretion of milk, and behavioral changes. The exact mechanism of the exaggerated prolactin response is unclear, but it may involve increased sensitivity of the pituitary to low progesterone levels or decreased dopaminergic inhibition. Dopamine normally inhibits prolactin secretion, and a relative dopamine deficiency may contribute. In cats, pseudopregnancy occurs after ovulation, and the corpus luteum secretes progesterone for about 30 to 40 days. Prolactin levels rise, but the clinical signs are usually mild, possibly due to lower prolactin receptor density or different hormonal regulation. The mammary gland changes are similar to those in pregnancy, with hyperplasia and secretion. Behavioral changes are mediated by prolactin and possibly oxytocin, which is involved in maternal bonding. The condition is self-limiting, but if milk stasis occurs, it can lead to mastitis.

Several factors predispose a bitch to develop pseudopregnancy. Intrinsic factors include breed susceptibility, with certain breeds like Beagles, Dachshunds, and toy breeds showing higher incidence. Nulliparity is a risk factor, as bitches that have never been pregnant are more likely to exhibit clinical signs. Age is also a factor, with young bitches in their first few cycles being more commonly affected. Hormonal imbalances, such as an exaggerated luteal phase or a rapid decline in progesterone, can predispose. Genetic factors may influence the sensitivity of the mammary gland to prolactin or the hypothalamic-pituitary axis. Extrinsic factors include the administration of exogenous progestins, which can cause iatrogenic pseudopregnancy when withdrawn. Stress, such as changes in environment or the presence of other pregnant/lactating females, may trigger or exacerbate signs. Poor breeding management, such as missing the optimal breeding time and not mating the bitch, increases the likelihood of pseudopregnancy. In cats, predisposing factors include being bred by an infertile male or having an induced ovulation without conception. Obesity may also increase the risk due to altered hormone metabolism.

Clinical signs of pseudopregnancy typically appear 6 to 12 weeks after estrus, corresponding to the time when a true pregnancy would be near term. The most common signs are mammary gland enlargement, which may be bilateral and symmetrical, and milk production (galactorrhea). The mammary glands may be warm, turgid, and sometimes painful. Behavioral changes include nesting behavior, such as gathering toys or other objects into a bed, mothering these objects, and sometimes aggression when the objects are removed. The bitch may become restless, anxious, or show signs of depression. Some bitches may exhibit abdominal distension due to fluid retention or fat deposition. Appetite may increase or decrease. In severe cases, there may be a slight vaginal discharge, but it is usually not purulent. Systemic signs such as fever are uncommon unless mastitis develops. In cats, signs are usually milder and may include mammary enlargement, milk production, and behavioral changes like increased affection or nesting. The signs are self-limiting and usually resolve within 2 to 3 weeks, but they can persist longer in some individuals.

The differential diagnoses for pseudopregnancy include true pregnancy, which can be ruled out by absence of fetal heartbeats on ultrasound or lack of fetal skeletons on radiographs after day 45. Pyometra is a critical differential, especially if there is vaginal discharge and systemic signs; ultrasound will show a fluid-filled uterus, and the bitch may have leukocytosis and fever. Mammary gland neoplasia can cause mammary enlargement, but it is usually nodular and may be unilateral; cytology or biopsy is definitive. Mastitis is characterized by painful, inflamed mammary glands, often with systemic signs, and may be secondary to pseudopregnancy. Galactorrhea due to other causes, such as hypothyroidism or prolactin-secreting tumors, is rare but possible. Ovarian cysts or tumors can cause hormonal imbalances and mimic pseudopregnancy. In cats, pregnancy, pyometra, and mammary neoplasia should be considered. Other conditions like obesity or ascites can cause abdominal distension. A thorough reproductive history, including breeding dates and estrous cycle timing, is essential. Diagnostic tests such as ultrasound, progesterone measurement, and vaginal cytology help differentiate these conditions.

The diagnostic approach to pseudopregnancy begins with a thorough history and physical examination. The clinician should confirm that the bitch is not pregnant by determining the time since estrus and any breeding history. If the bitch was not bred, pseudopregnancy is likely. If she was bred, pregnancy should be ruled out. The diagnostic algorithm proceeds as follows: 1) Perform a complete physical examination, focusing on the mammary glands, abdomen, and vulva. 2) Obtain a vaginal cytology to assess the stage of the estrous cycle; in pseudopregnancy, the cytology will show a diestrus pattern with predominantly parabasal and intermediate cells, and no cornified cells. 3) Measure serum progesterone levels; in pseudopregnancy, progesterone will be elevated (typically >2 ng/mL) during the luteal phase, but it will decline as the condition progresses. 4) Perform abdominal ultrasonography to evaluate the uterus and ovaries; in pseudopregnancy, the uterus may be slightly enlarged but empty, and the ovaries may contain corpora lutea. 5) If pregnancy is suspected, radiography after day 45 can confirm the absence of fetal skeletons. 6) If there is any vaginal discharge or systemic signs, consider pyometra and perform a complete blood count and biochemistry. 7) If mammary gland abnormalities are present, fine-needle aspiration or biopsy may be indicated. 8) In cases of recurrent or severe pseudopregnancy, hormonal assays including prolactin levels may be helpful, though they are not routinely measured.

In pseudopregnancy, laboratory findings are generally unremarkable. Serum progesterone levels are elevated during the luteal phase, typically ranging from 4 to 15 ng/mL, but they decline to <1 ng/mL by the end of the luteal phase. Prolactin levels may be elevated, but this is not routinely measured. Complete blood count is usually normal, but if mastitis is present, there may be leukocytosis with a left shift. Biochemistry profile is typically normal. Vaginal cytology shows a diestrus pattern with a predominance of parabasal and intermediate cells, and no superficial cells. There may be some neutrophils and bacteria, but this is normal. If pyometra is a differential, the white blood cell count may be elevated, and there may be hyperglobulinemia. Urinalysis is usually normal. Hormonal assays for thyroid function may be considered if hypothyroidism is suspected as a cause of galactorrhea. In cats, similar findings are expected, but progesterone levels may be lower.

Imaging is crucial to rule out pregnancy and other uterine pathology. Abdominal ultrasonography is the preferred method. In pseudopregnancy, the uterus may appear slightly enlarged with a thickened endometrium, but there are no fetal structures. The ovaries may contain corpora lutea, which appear as hypoechoic structures. The uterine lumen is typically empty, with no fluid accumulation. If pyometra is present, the uterus will be distended with anechoic or echogenic fluid. Radiography can be used after day 45 of gestation to confirm the absence of fetal skeletons; in pseudopregnancy, no fetal mineralization is seen. Radiography is less useful for soft tissue evaluation but can help rule out other causes of abdominal distension. CT and MRI are rarely needed but may be used to evaluate the pituitary gland if a prolactinoma is suspected. Vaginoscopy can be performed to assess the vaginal mucosa, but it is not typically necessary. Doppler ultrasound can be used to measure uterine artery blood flow, but this is not standard.

Vaginal cytology is a key diagnostic tool. In pseudopregnancy, the cytology shows a diestrus pattern: the predominant cells are parabasal and intermediate cells, with few or no superficial cells. There may be a background of mucus and bacteria. This pattern is consistent with the luteal phase. If the bitch is in proestrus or estrus, the cytology would show a high percentage of superficial cells. Fine-needle aspiration of the mammary gland may be performed if there is a mass or if mastitis is suspected. In pseudopregnancy, the aspirate may show benign mammary epithelial cells, often with secretory material. If mastitis is present, there will be neutrophils and bacteria. Histopathology is rarely needed but may be performed if mammary neoplasia is suspected. In such cases, a biopsy would show the characteristic features of the tumor. Endometrial biopsy is not indicated for pseudopregnancy.

Treatment for pseudopregnancy is only necessary if clinical signs are severe or if the condition is recurrent and affects the dog's quality of life. In many cases, the condition is self-limiting and resolves within 2 to 3 weeks. Supportive care includes reducing the dog's food intake slightly and limiting water intake to decrease milk production, but this is controversial. Applying cold compresses to the mammary glands can provide relief. If the dog is licking the mammary glands excessively, an Elizabethan collar may be used. Medical treatment is indicated for severe signs. The most effective treatment is the use of prolactin inhibitors, such as cabergoline (5 mcg/kg PO q24h for 5-7 days) or bromocriptine (10-30 mcg/kg PO q12h for 10-14 days). These drugs reduce prolactin levels and rapidly resolve clinical signs. Alternatively, aglepristone (10 mg/kg SC on days 1, 2, and 8) can be used as a progesterone receptor antagonist, but it is less commonly used. In cases of severe mastitis, antibiotics and anti-inflammatory drugs may be needed. Ovariohysterectomy is the definitive treatment for bitches that are not intended for breeding, as it prevents recurrence. However, surgery should be delayed until the luteal phase is over to avoid complications. In cats, treatment is rarely needed, but cabergoline can be used if signs are severe.

The prognosis for pseudopregnancy is excellent. The condition is self-limiting and resolves without treatment in most cases. With medical treatment, clinical signs typically resolve within a few days. The main concern is recurrence with each estrous cycle, which can be distressing for the owner. If the bitch is not intended for breeding, ovariohysterectomy is curative. If the bitch is intended for breeding, the condition does not affect fertility; in fact, bitches that have pseudopregnancy are often fertile. However, if mastitis develops, it can lead to mammary gland damage and potentially affect future lactation. The prognosis for cats is also excellent, with rare complications. Negative prognostic indicators include the development of mastitis or the presence of an underlying endocrine disorder, such as hypothyroidism. Overall, the long-term prognosis is very good.

Follow-up for pseudopregnancy depends on the treatment approach. If no treatment is given, the owner should monitor the dog for resolution of signs within 2 to 3 weeks. If medical treatment is used, a recheck examination is recommended 1 to 2 weeks after the start of treatment to ensure that clinical signs have resolved and to monitor for side effects. If the dog is treated with cabergoline, a follow-up visit may be scheduled after the 5-day course to confirm resolution. If ovariohysterectomy is performed, routine postoperative care is required, and the dog should be rechecked in 10 to 14 days for suture removal. For breeding management, the owner should be advised to monitor the next estrous cycle and consider breeding if desired. Serial progesterone measurements may be recommended to time breeding accurately. If the dog has recurrent pseudopregnancy, the owner may consider ovariohysterectomy. In cats, follow-up is usually not necessary unless signs persist.

Clinical pearls: 1) Pseudopregnancy is a normal physiological event in the bitch, and treatment is only needed if signs are severe. 2) The onset of signs typically occurs 6-12 weeks after estrus, which is the time of luteal regression. 3) Cabergoline is the drug of choice for treatment due to its efficacy and minimal side effects. 4) Ovariohysterectomy is the definitive treatment for non-breeding bitches. 5) Always rule out pregnancy before diagnosing pseudopregnancy. Pitfalls: 1) Misdiagnosing pyometra as pseudopregnancy, especially if there is vaginal discharge; always perform ultrasound. 2) Using progestins to treat pseudopregnancy, which can cause cystic endometrial hyperplasia and pyometra. 3) Performing ovariohysterectomy during the luteal phase, which can be more complicated due to increased uterine size and vascularity. 4) Overlooking mastitis, which can be a complication. 5) Failing to consider other causes of galactorrhea, such as hypothyroidism.

The following drug protocols are based on Plumb's Veterinary Drug Handbook and theriogenology guidelines. For pseudopregnancy, the primary treatment is cabergoline (Galastop) at a dose of 5 mcg/kg PO q24h for 5-7 days. It is a dopamine agonist that inhibits prolactin secretion. Side effects are rare but may include vomiting and anorexia. Bromocriptine (Parlodel) is an alternative, but it has more side effects; dose is 10-30 mcg/kg PO q12h for 10-14 days. Aglepristone (Alizin) is a progesterone receptor antagonist that can be used at 10 mg/kg SC on days 1, 2, and 8. It is effective but may cause local reactions. For mastitis, antibiotics such as amoxicillin-clavulanate (12.5-25 mg/kg PO q8h) or cephalexin (22 mg/kg PO q8h) are indicated. Non-steroidal anti-inflammatory drugs like carprofen (2.2 mg/kg PO q12h) can be used for pain and inflammation. If the dog is to be bred, no treatment is recommended. For cats, cabergoline can be used at the same dose, but treatment is rarely needed.

The literature on pseudopregnancy is extensive. Key studies include those by Johnston, Kustritz, and Olson in 'Canine and Feline Theriogenology' which provide a comprehensive overview of the condition. They emphasize that pseudopregnancy is a normal physiological event and that treatment should be reserved for severe cases. Studies on cabergoline have shown it to be highly effective in reducing prolactin levels and resolving clinical signs within 3-5 days. A study by Onclin and Verstegen (1999) demonstrated that aglepristone is also effective. The use of progestins is discouraged due to the risk of pyometra. The ACT (American College of Theriogenologists) and EVSSAR (European Veterinary Society for Small Animal Reproduction) have published guidelines on the management of pseudopregnancy, recommending cabergoline as the first-line treatment. In cats, pseudopregnancy is less studied, but the same principles apply. Overall, the evidence supports a conservative approach, with medical intervention only when necessary.