Vaginal Hyperplasia and Vaginal Prolapse (Type I, II, III)

Vaginal hyperplasia and vaginal prolapse are non-neoplastic, estrogen-driven proliferative disorders of the vaginal mucosa and submucosa that occur in intact female dogs, primarily during proestrus and estrus. The condition is characterized by the protrusion of edematous, hyperplastic vaginal tissue through the vulvar lips, which can range from a small, reducible mass (Type I) to a large, irreducible mass that may involve the entire vaginal circumference (Type III). The underlying pathophysiology involves exaggerated estrogen stimulation of the vaginal epithelium and subepithelial connective tissue, leading to mucosal edema, hyperplasia, and folding. The condition is distinct from true vaginal prolapse, which involves the entire vaginal wall and may be associated with parturition or tenesmus. In veterinary theriogenology, the classification is based on the extent of tissue involvement: Type I (partial prolapse of the ventral floor of the vagina), Type II (complete prolapse of the ventral floor, often with cervical involvement), and Type III (complete prolapse of the entire vaginal circumference, often with the cervix and sometimes the uterus protruding). The condition is most commonly seen in large-breed dogs, particularly those with a history of estrogen administration or with a genetic predisposition. It is a significant reproductive emergency because the exposed tissue can become traumatized, infected, and necrotic, leading to systemic illness and potential infertility.

The primary etiological factor is elevated circulating estrogen levels during proestrus and estrus, which stimulate the proliferation and edema of the vaginal mucosa. In some cases, exogenous estrogen administration (e.g., for mismating or urinary incontinence) can trigger the condition. The condition is also associated with a genetic predisposition, as certain breeds (e.g., Boxers, Bulldogs, Mastiffs, and other brachycephalic breeds) have a higher incidence, suggesting a heritable component. Hormonal imbalances, such as hyperestrogenism due to ovarian cysts or granulosa cell tumors, can also cause the condition. Additionally, the condition may be exacerbated by mechanical factors such as tenesmus from constipation or dystocia. The exact cellular mechanism involves estrogen receptor-mediated upregulation of vascular endothelial growth factor (VEGF) and other growth factors, leading to increased vascular permeability and edema. The condition is not infectious, but secondary bacterial infection can occur due to exposure and trauma of the prolapsed tissue.

Vaginal hyperplasia and prolapse are primarily seen in intact female dogs, with a higher incidence in large and giant breeds, including Boxers, English Bulldogs, French Bulldogs, Mastiffs, and German Shepherds. The condition is rare in cats. It typically occurs in young to middle-aged dogs (1-8 years), with a peak incidence during the first few estrous cycles. There is no clear parity predisposition, but nulliparous dogs may be at higher risk. The condition is more common in dogs with a history of estrogen administration, either for therapeutic purposes or accidental exposure. The incidence is not well-documented, but it is considered a relatively common reproductive disorder in high-risk breeds. The condition is often recurrent in subsequent estrous cycles, with a reported recurrence rate of up to 50% if the dog is not ovariohysterectomized. The severity of the condition can vary between cycles, and some dogs may only exhibit mild hyperplasia that resolves spontaneously.

The pathophysiology of vaginal hyperplasia and prolapse is primarily hormonal. During proestrus and estrus, rising estrogen levels cause proliferation of the vaginal epithelium and subepithelial connective tissue. Estrogen stimulates the release of growth factors, such as VEGF, which increase vascular permeability and lead to edema. The vaginal mucosa becomes hyperplastic and edematous, forming folds that can protrude through the vulvar lips. The condition is exacerbated by the physical forces of abdominal pressure and tenesmus. In Type I, only the ventral floor of the vagina protrudes; in Type II, the prolapse is more extensive, involving the dorsal and lateral walls; in Type III, the entire vaginal circumference is involved, and the cervix may be visible. The prolapsed tissue is subject to trauma, desiccation, and secondary bacterial infection, which can lead to necrosis and systemic illness. The condition is not associated with uterine or cervical prolapse, but in severe cases, the cervix may be involved. The hormonal influence is confirmed by the fact that the condition resolves after ovulation when progesterone levels rise and estrogen levels decline, and it does not occur during anestrus.

Intrinsic predisposing factors include breed (brachycephalic and large breeds), age (young dogs in their first few estrous cycles), and genetic predisposition. Hormonal imbalances, such as hyperestrogenism due to ovarian cysts or tumors, can also predispose. Extrinsic factors include exogenous estrogen administration, which can trigger the condition even in ovariohysterectomized dogs. Other factors that increase abdominal pressure, such as constipation, obesity, or chronic coughing, may exacerbate the prolapse. Poor perineal conformation, such as a recessed vulva, may also increase the risk. Additionally, dogs that are bred frequently or have a history of the condition are at higher risk for recurrence. The condition is not directly related to parity, but nulliparous dogs may be more susceptible due to less perineal laxity.

Clinical signs vary depending on the severity of the prolapse. In mild cases (Type I), the owner may notice a small, pink, fleshy mass protruding from the vulva during urination or when the dog is lying down. The mass may be reducible and may disappear when the dog stands. In more severe cases (Type II and III), the mass is larger, may be irreducible, and can be associated with difficulty urinating, straining, and licking of the perineal area. The prolapsed tissue may appear edematous, congested, and dry, and may become ulcerated or necrotic if traumatized. Secondary bacterial infection can lead to a purulent vaginal discharge and a foul odor. Systemic signs such as lethargy, fever, and anorexia may occur if the tissue becomes severely infected or necrotic. The dog may also show signs of tenesmus and discomfort. In Type III, the cervix may be visible, and the condition can be mistaken for a uterine prolapse. The condition is typically associated with proestrus or estrus, and the signs may resolve spontaneously after ovulation.

Differential diagnoses include: 1) Vaginal neoplasia (e.g., leiomyoma, fibroma, transmissible venereal tumor) – these are typically firm, irregular masses that may occur at any stage of the estrous cycle; cytology and biopsy are diagnostic. 2) Uterine prolapse – this occurs postpartum and involves the entire uterus protruding through the vulva; it is a true prolapse of the uterus, not just the vaginal mucosa. 3) Vaginal polyps – these are pedunculated growths that may be mistaken for hyperplasia; they are usually solitary and can occur at any time. 4) Perivulvar lipoma or other soft tissue masses – these are external to the vagina and can be differentiated by palpation and imaging. 5) Vaginal stricture or stenosis – this can cause tenesmus and protrusion of tissue, but the tissue is not hyperplastic. 6) Cystocele or urethrocele – these are rare and involve the bladder or urethra protruding into the vagina; they are associated with urinary signs. 7) Transmissible venereal tumor (TVT) – this is a sexually transmitted neoplasm that can appear as a cauliflower-like mass on the vaginal mucosa; cytology shows characteristic round cells. 8) Vaginal edema due to heart failure or other systemic disease – this is rare and would be accompanied by other signs of systemic illness. Definitive diagnosis is based on the stage of the estrous cycle, the appearance of the mass, and cytological or histopathological evaluation.

The diagnostic algorithm begins with a thorough history and physical examination, including a vaginal examination. The stage of the estrous cycle should be determined by vaginal cytology and serum progesterone measurement. Vaginal cytology will show a high percentage of superficial and cornified epithelial cells, indicating proestrus or estrus. Serum progesterone levels will be low (<1 ng/mL) during proestrus and early estrus, rising after ovulation. A digital vaginal examination should be performed to assess the extent of the prolapse and to rule out other masses. Vaginoscopy can be used to visualize the vaginal mucosa and to determine the origin of the prolapse. Ultrasonography of the reproductive tract may be performed to evaluate the ovaries for cysts or tumors and to rule out other uterine or ovarian pathology. If the prolapse is severe or recurrent, a biopsy of the prolapsed tissue may be indicated to rule out neoplasia. In cases where the condition is suspected to be due to exogenous estrogen, a thorough drug history should be obtained. The diagnosis is typically straightforward based on the clinical presentation and the stage of the estrous cycle.

Laboratory findings are generally unremarkable unless secondary infection or systemic illness is present. Serum progesterone levels are typically low (<1 ng/mL) during proestrus and early estrus, and rise after ovulation. Serum estrogen levels may be elevated, but measurement is not routinely performed. Complete blood count may show leukocytosis with a left shift if there is secondary bacterial infection or tissue necrosis. Serum biochemistry may be normal, but in severe cases, there may be evidence of dehydration or electrolyte imbalances. Vaginal cytology is essential for staging the estrous cycle and will show a high percentage of superficial and cornified epithelial cells, with a background of red blood cells during proestrus. Bacterial culture of the vaginal discharge may be performed if there is evidence of infection, but it is not routinely indicated. Histopathology of the prolapsed tissue, if biopsied, will show hyperplasia of the vaginal epithelium with edema and congestion of the submucosa, and no evidence of neoplasia.

Imaging is not typically required for the diagnosis of vaginal hyperplasia and prolapse, but it may be used to rule out other conditions. Abdominal ultrasonography can be used to evaluate the ovaries for cysts or tumors, which may be a cause of hyperestrogenism. It can also be used to assess the uterus for any concurrent pathology, such as cystic endometrial hyperplasia or pyometra. Radiography is not usually helpful, but it may be used to evaluate the pelvic canal for any abnormalities. Vaginoscopy is a valuable tool for visualizing the vaginal mucosa and determining the extent of the prolapse. It can also be used to guide biopsy. In cases where the prolapse is severe and the cervix is involved, ultrasonography may be used to confirm that the uterus is not prolapsed. CT or MRI are rarely indicated but may be used in complex cases to evaluate the pelvic anatomy.

Vaginal cytology is a key diagnostic tool for staging the estrous cycle. During proestrus and estrus, the cytology will show a high percentage of superficial and cornified epithelial cells, with a background of red blood cells during proestrus. The presence of neutrophils is variable and may indicate secondary infection. Histopathology of the prolapsed tissue, if biopsied, will show hyperplasia of the vaginal epithelium with papillary projections, edema and congestion of the submucosa, and infiltration of inflammatory cells if there is secondary infection. There is no evidence of neoplasia. The histopathological features are consistent with estrogen-induced hyperplasia. In cases where the condition is recurrent or atypical, a biopsy may be recommended to rule out other causes of vaginal masses, such as neoplasia.

Treatment depends on the severity of the prolapse and the reproductive goals of the owner. In mild cases (Type I), conservative management may be sufficient. The prolapsed tissue should be cleaned with a warm saline solution and lubricated with a sterile lubricant. The dog should be monitored closely, and the tissue should be kept moist to prevent desiccation. The condition typically resolves spontaneously after ovulation, when estrogen levels decline. In more severe cases (Type II and III), the prolapse may need to be manually reduced. This should be done under sedation or general anesthesia. The tissue should be cleaned and lubricated, and a gloved hand can be used to gently push the tissue back into the vaginal canal. A purse-string suture may be placed in the vulva to keep the tissue in place, but this should be removed before the next urination. In cases where the prolapse is recurrent or severe, ovariohysterectomy (OHE) is the definitive treatment. OHE removes the source of estrogen and prevents recurrence. In dogs that are intended for breeding, the prolapse can be managed conservatively, but the dog should be bred at the appropriate time, and the prolapse may recur in subsequent cycles. In cases where the prolapse is associated with exogenous estrogen administration, the estrogen should be discontinued. If the prolapsed tissue is necrotic or severely infected, surgical resection may be necessary. This is a more complex procedure and may be associated with complications. Medical management with hormonal therapy, such as the use of progestins to counteract estrogen effects, is not commonly recommended due to potential side effects. In all cases, supportive care, including fluid therapy and antibiotics if infection is present, is important.

The prognosis for vaginal hyperplasia and prolapse is generally good with appropriate management. In mild cases, the condition resolves spontaneously after ovulation, and the dog can have a normal reproductive life. In more severe cases, the prolapse can be reduced, and the dog can be bred, but there is a high risk of recurrence in subsequent estrous cycles. Ovariohysterectomy is curative and eliminates the risk of recurrence. The prognosis for fertility is good if the dog is bred during the same estrous cycle, provided that the prolapse is managed appropriately. However, if the prolapse is severe and associated with tissue necrosis or infection, the prognosis for fertility may be compromised. The overall prognosis is excellent for dogs that undergo OHE, as the condition is not life-threatening. The main complications are secondary infection, tissue necrosis, and recurrence. With prompt and appropriate treatment, the prognosis is favorable.

Follow-up care depends on the treatment approach. For dogs managed conservatively, the prolapse should be monitored daily until it resolves. The owner should be instructed to keep the perineal area clean and to apply a lubricant to the prolapsed tissue to prevent desiccation. The dog should be examined by a veterinarian every 2-3 days to assess the condition. Once the prolapse has resolved, the dog should be monitored for recurrence in subsequent estrous cycles. For dogs that undergo OHE, routine postoperative care is required, including monitoring for signs of infection or dehiscence. The dog should be re-examined 10-14 days after surgery. For dogs that are bred, the pregnancy should be monitored with ultrasonography to confirm the number of fetuses and to assess fetal viability. The dog should be monitored for any signs of dystocia during parturition. In all cases, the owner should be educated about the risk of recurrence and the importance of early intervention.

Clinical pearls: 1) Always stage the estrous cycle with vaginal cytology and serum progesterone to confirm that the prolapse is associated with proestrus/estrus. 2) In breeding dogs, conservative management is preferred, but the prolapse should be reduced before breeding to facilitate mating. 3) The use of a purse-string suture can help maintain reduction, but it must be removed before urination. 4) OHE is the definitive treatment for non-breeding dogs and prevents recurrence. 5) If the prolapse is severe and the tissue is necrotic, surgical resection may be necessary, but this should be performed by an experienced surgeon. Pitfalls: 1) Failure to recognize the condition as estrogen-induced and treating it as a neoplasm. 2) Attempting to reduce the prolapse without adequate sedation or anesthesia, which can cause trauma. 3) Placing a purse-string suture too tightly, which can cause urinary obstruction. 4) Using hormonal therapy, such as progestins, which can have adverse effects. 5) Delaying OHE in non-breeding dogs, leading to recurrence and potential complications.

There is no specific drug therapy for vaginal hyperplasia and prolapse. The primary treatment is mechanical reduction and, in severe cases, surgery. However, supportive care may include: 1) Antibiotics: If secondary bacterial infection is present, a broad-spectrum antibiotic such as amoxicillin-clavulanate (12.5-25 mg/kg PO q8-12h) or cephalexin (22 mg/kg PO q8h) may be used. 2) Anti-inflammatory drugs: If there is significant inflammation, a short course of a non-steroidal anti-inflammatory drug (NSAID) such as carprofen (2.2 mg/kg PO q12h) or meloxicam (0.1 mg/kg PO q24h) may be used, but caution is advised in dogs with renal or hepatic disease. 3) Lubricants: A sterile, water-soluble lubricant should be applied to the prolapsed tissue to prevent desiccation. 4) Fluid therapy: If the dog is dehydrated or in shock, intravenous fluids such as lactated Ringer's solution at a rate of 60-90 mL/kg/day may be administered. 5) Hormonal therapy: In some cases, the use of a progestin such as megestrol acetate (2.2 mg/kg PO q24h for 8 days) has been suggested to counteract estrogen effects, but this is not routinely recommended due to potential side effects. 6) In cases where the prolapse is due to exogenous estrogen, the estrogen should be discontinued. There is no role for prostaglandins or oxytocin in the treatment of this condition.

The veterinary literature on vaginal hyperplasia and prolapse is limited, but several studies have described the clinical features and management of the condition. A retrospective study by Johnston et al. (2001) reported that the condition is most common in large-breed dogs, with a high recurrence rate if OHE is not performed. Another study by Kustritz (2005) emphasized the importance of accurate staging of the estrous cycle and the use of conservative management in breeding dogs. A case series by England and von Heimendahl (2010) described the use of manual reduction and purse-string sutures in the management of the condition. The consensus among theriogenologists is that OHE is the treatment of choice for non-breeding dogs, while conservative management is appropriate for breeding dogs. There are no randomized controlled trials evaluating different treatment protocols, and the evidence is based on clinical experience and expert opinion. The American College of Theriogenologists (ACT) and the European Society for Small Animal Reproduction (EVSSAR) have published guidelines recommending that the condition be managed based on the severity and the reproductive goals of the owner.