Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) is a non-inflammatory, non-neoplastic enlargement of the prostate gland that occurs in intact male dogs, and less commonly in other species such as cats and horses. It is the most common prostatic disorder in dogs, with a high prevalence in middle-aged to older intact males. The condition is characterized by an increase in both the number and size of prostatic epithelial and stromal cells, leading to glandular hyperplasia and stromal proliferation. BPH is primarily driven by androgens, particularly dihydrotestosterone (DHT), which is synthesized locally from testosterone by the enzyme 5-alpha-reductase. The prostate gland in dogs is a bilobed, ovoid structure located caudal to the bladder, encircling the urethra. BPH typically results in symmetrical, non-painful prostatic enlargement, which may be asymptomatic or cause clinical signs such as tenesmus, dysuria, and bloody or sanguineous urethral discharge. The condition is distinct from prostatitis, prostatic abscess, and prostatic neoplasia, although it can coexist with these conditions. In cats, BPH is rare, but when present, it is often associated with androgen-secreting tumors or exogenous androgen administration. In stallions, BPH is uncommon but may occur with advancing age. The clinical significance of BPH lies in its potential to cause lower urinary tract signs, reproductive dysfunction, and its role as a predisposing factor for prostatitis and prostatic abscessation.

The primary etiological factor in the development of BPH is the presence of androgens, specifically testosterone and its potent metabolite dihydrotestosterone (DHT). Testosterone is produced by the Leydig cells of the testes and is converted to DHT within the prostate by the enzyme 5-alpha-reductase type 2. DHT binds to androgen receptors in prostatic stromal and epithelial cells, leading to the activation of growth factors such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and transforming growth factor-beta (TGF-beta), which promote cellular proliferation and inhibit apoptosis. The role of estrogens is also significant; in older dogs, there is an increase in the estrogen-to-testosterone ratio, which may synergize with androgens to induce prostatic hyperplasia. Estrogens can upregulate androgen receptors and enhance the sensitivity of prostatic tissue to DHT. Additionally, prolactin has been implicated in the regulation of prostatic growth, although its exact role is less defined. Genetic factors may contribute to individual susceptibility, but no specific genetic mutations have been identified in dogs. Iatrogenic causes include the administration of exogenous androgens or anabolic steroids, which can induce or exacerbate BPH. In cats, BPH is rare and is often associated with androgen-secreting testicular tumors or exogenous androgen therapy. In stallions, BPH may be related to age-related hormonal changes. Infectious agents are not directly involved in the etiology of BPH, but secondary bacterial infection can occur due to urinary stasis and altered prostatic secretions.

BPH is the most common prostatic disease in intact male dogs, with a prevalence that increases with age. Studies have shown that approximately 50% of intact male dogs over 5 years of age have histological evidence of BPH, and nearly all intact males over 9 years of age are affected. Clinical signs are present in about 30% of dogs with BPH. There is no strong breed predisposition, but large-breed dogs may be overrepresented due to their longer lifespan and higher likelihood of being kept intact. The condition is rare in cats, with only sporadic case reports, often associated with testicular neoplasia or exogenous androgen administration. In stallions, BPH is uncommon but may occur in older animals. The condition is exclusively seen in intact males, as castration leads to prostatic atrophy. The incidence of BPH is not influenced by parity or breeding status, but it is more likely to be clinically significant in dogs used for breeding due to the potential impact on semen quality and libido. In a study of 100 intact male dogs, the prevalence of BPH was 52% in dogs aged 5-7 years, 75% in dogs aged 8-10 years, and 100% in dogs over 10 years. The condition is often underdiagnosed because many dogs are asymptomatic, and routine screening is not commonly performed.

The pathophysiology of BPH involves a complex interplay of hormonal, cellular, and molecular mechanisms. The prostate gland is composed of glandular (epithelial) and stromal (fibromuscular) components. In BPH, there is a proliferation of both epithelial and stromal cells, with the stromal component often predominating. The process is initiated by the binding of DHT to androgen receptors in the nucleus of prostatic cells. This binding activates transcription of genes encoding growth factors and their receptors, leading to increased cell proliferation and decreased apoptosis. The balance between cell proliferation and apoptosis is disrupted, resulting in net tissue growth. Estrogens, which increase in relative concentration with age, may act synergistically with androgens by inducing the expression of androgen receptors and by stimulating the production of growth factors such as FGF. Additionally, estrogens may cause squamous metaplasia of the prostatic epithelium, which can contribute to glandular enlargement. The enlarged prostate compresses the prostatic urethra, leading to partial urinary obstruction, which can cause dysuria, stranguria, and urinary retention. The increased size of the prostate may also cause tenesmus due to compression of the colon. The prostatic parenchyma becomes hyperplastic, with the formation of multiple cysts in some cases. These cysts may become infected, leading to prostatitis or abscessation. The vascularity of the prostate is increased, and the gland may become more susceptible to hemorrhage, resulting in sanguineous urethral discharge. In dogs, BPH does not typically progress to malignancy, but it can coexist with prostatic carcinoma, which is a separate entity.

The primary predisposing factor for BPH is intact male status, as the condition does not occur in castrated animals. Age is a significant risk factor, with the prevalence and severity of BPH increasing with advancing age. The condition is most commonly diagnosed in dogs over 5 years of age, with a peak incidence in the 7-10 year age range. Breed may play a role, with some studies suggesting that large-breed dogs such as German Shepherds, Boxers, and Doberman Pinschers may be at higher risk, although this is not consistently reported. Genetic factors may influence individual susceptibility, but no specific genetic markers have been identified. Hormonal imbalances, such as an increased estrogen-to-testosterone ratio, are thought to contribute to the development of BPH in older dogs. Exogenous administration of androgens or anabolic steroids can induce BPH in intact or even castrated animals. Obesity may be a risk factor due to increased peripheral conversion of androgens to estrogens in adipose tissue. Environmental factors such as chronic stress or poor nutrition may indirectly affect hormonal balance, but there is limited evidence to support a direct link. In cats, BPH is rare and is typically associated with testicular neoplasia (e.g., Sertoli cell tumors) or exogenous androgen therapy. In stallions, age is the primary risk factor, and BPH is more common in breeding stallions due to the higher levels of testosterone.

Clinical signs of BPH are variable and depend on the degree of prostatic enlargement and the presence of complications. Many dogs with BPH are asymptomatic, and the condition is often an incidental finding on physical examination or imaging. When clinical signs are present, they are primarily related to the effects of prostatic enlargement on the urinary and gastrointestinal systems. Common signs include tenesmus (straining to defecate), dysuria (difficult or painful urination), stranguria (slow or intermittent urination), and hematuria (blood in the urine). A sanguineous or serosanguineous urethral discharge, often noted as blood dripping from the prepuce, is a classic sign of BPH. The discharge is not associated with urination and may be intermittent. In some cases, the enlarged prostate may cause constipation due to compression of the rectum. Dogs may also show signs of discomfort or pain during defecation or urination. On physical examination, a symmetrically enlarged, non-painful prostate is palpable on rectal palpation. The prostate may be located more cranially in the abdomen in some cases, making it difficult to palpate rectally. In severe cases, the prostate may be large enough to be palpated abdominally. Systemic signs such as fever, lethargy, and anorexia are not typical of uncomplicated BPH but may occur if secondary prostatitis or abscessation develops. In breeding dogs, BPH may be associated with decreased libido, poor semen quality, and hematospermia (blood in the semen). In cats, clinical signs are similar but may be less common due to the rarity of the condition.

The differential diagnoses for BPH include other prostatic diseases and conditions that cause similar clinical signs. These include: 1) Prostatitis (acute or chronic bacterial infection of the prostate), which is characterized by fever, lethargy, and a painful prostate on palpation, with systemic signs of infection. 2) Prostatic abscess, which presents with severe systemic illness, fever, and a fluctuant, painful prostate, often with leukocytosis and sepsis. 3) Prostatic neoplasia (adenocarcinoma), which is more common in older dogs and may present with weight loss, dysuria, and a firm, irregular prostate with possible metastasis to regional lymph nodes or bone. 4) Paraprostatic cysts, which are fluid-filled structures adjacent to the prostate, often causing tenesmus and dysuria, and may be palpable as a large abdominal mass. 5) Urethritis or cystitis, which can cause dysuria and hematuria but without prostatic enlargement. 6) Urinary tract calculi, which may cause similar urinary signs but are typically diagnosed via radiography or ultrasonography. 7) Benign prostatic cysts, which are often incidental findings but can cause clinical signs if large. 8) Squamous metaplasia of the prostate, which is associated with Sertoli cell tumors or exogenous estrogen administration, and may present with feminization signs. 9) Prostatic retention cysts, which are often associated with BPH but can be differentiated by ultrasonography. 10) In cats, testicular neoplasia with androgen production should be considered. Definitive diagnosis of BPH is based on ruling out these conditions through a combination of physical examination, imaging, cytology, and histopathology.

The diagnostic approach to BPH should be systematic and include the following steps: 1) Signalment and history: Note the age, breed, and intact status of the animal. Ask about clinical signs such as tenesmus, dysuria, hematuria, and urethral discharge. 2) Physical examination: Perform a thorough examination, including rectal palpation of the prostate to assess size, symmetry, pain, and consistency. 3) Urinalysis: Collect a urine sample via cystocentesis to rule out urinary tract infection and to assess for hematuria or pyuria. 4) Complete blood count (CBC) and serum biochemistry: These are useful to rule out systemic infection or other metabolic abnormalities. 5) Imaging: Abdominal radiography may show an enlarged prostate, but ultrasonography is the preferred imaging modality. Ultrasonography can assess prostatic size, symmetry, echogenicity, and the presence of cysts or abscesses. 6) Prostatic fluid evaluation: If prostatitis is suspected, prostatic fluid can be obtained by ejaculation or prostatic massage for cytology and culture. 7) Fine-needle aspiration (FNA) of the prostate: This can be performed under ultrasound guidance to obtain cells for cytology, which can help differentiate BPH from neoplasia or prostatitis. 8) Biopsy: If FNA is inconclusive or neoplasia is suspected, a biopsy may be performed via Tru-Cut needle or surgical biopsy. 9) Hormonal assays: Measurement of serum testosterone or DHT is not routinely necessary for diagnosis but may be helpful in cases of suspected hormonal imbalance. 10) Response to therapy: In many cases, a presumptive diagnosis of BPH is made based on clinical signs and imaging findings, and the response to castration or medical therapy (e.g., finasteride) can confirm the diagnosis. The diagnostic algorithm should be tailored to the individual case, with more invasive procedures reserved for cases where the diagnosis is uncertain or where complications are suspected.

Laboratory findings in BPH are often unremarkable unless there is a secondary infection or other concurrent disease. Complete blood count (CBC) is typically within normal limits in uncomplicated BPH. If prostatitis is present, there may be leukocytosis with a left shift, and toxic neutrophils may be seen. Serum biochemistry is usually normal, but in cases of urinary obstruction, there may be azotemia (elevated BUN and creatinine) and hyperphosphatemia. Urinalysis may reveal hematuria, pyuria, or bacteriuria if there is a concurrent urinary tract infection. Prostatic fluid evaluation, obtained via ejaculation or prostatic massage, may show increased numbers of red blood cells and neutrophils, but in uncomplicated BPH, the fluid is often normal. Hormonal assays are not routinely performed, but serum testosterone levels may be within the normal range for intact males. In cases of suspected estrogen-secreting tumors, serum estrogen levels may be elevated. Vaginal cytology is not applicable in males. In cats, similar findings may be present, but the condition is rare. Overall, laboratory findings are nonspecific and are primarily used to rule out other conditions such as prostatitis or neoplasia.

Imaging plays a crucial role in the diagnosis and management of BPH. Abdominal radiography may show an enlarged prostate, which appears as a soft tissue mass in the caudal abdomen, dorsal to the bladder. The prostate may be displaced cranially or dorsally. Radiography is not sensitive for detecting early BPH, and the size of the prostate can be difficult to assess accurately. Ultrasonography is the imaging modality of choice for evaluating the prostate. On ultrasound, the normal prostate is a bilobed, homogeneous structure with medium echogenicity. In BPH, the prostate is symmetrically enlarged, with a smooth contour and homogeneous echotexture. There may be multiple small anechoic cysts within the parenchyma, which are characteristic of BPH. The prostatic urethra may be compressed, and the bladder may be displaced cranially. Ultrasonography can also be used to guide fine-needle aspiration or biopsy. In cases of prostatitis or abscess, the prostate may appear heterogeneous with hypoechoic or hyperechoic areas, and abscesses appear as cavitated lesions with thick walls. Computed tomography (CT) and magnetic resonance imaging (MRI) are not commonly used for BPH but may be helpful in complex cases, particularly to assess for metastasis in suspected neoplasia. Vaginoscopy is not applicable in males. In cats, ultrasonography is also the preferred imaging modality. Overall, ultrasonography is essential for confirming the diagnosis of BPH and for monitoring response to therapy.

Cytological and histopathological evaluation is important for confirming the diagnosis of BPH and for ruling out other conditions. Fine-needle aspiration (FNA) of the prostate can be performed under ultrasound guidance. In BPH, cytology typically shows clusters of benign prostatic epithelial cells with uniform nuclei and abundant cytoplasm. There may be some cellular atypia, but it is not marked. The presence of inflammatory cells, such as neutrophils, suggests prostatitis. Histopathology of prostatic tissue, obtained via biopsy, is the gold standard for diagnosis. In BPH, the histological features include hyperplasia of the glandular epithelium, with an increase in the number and size of acini. The acini may be dilated and contain eosinophilic secretion. There is also proliferation of the stromal component, with an increase in smooth muscle and fibrous tissue. The overall architecture of the prostate is preserved, and there is no evidence of invasion or metastasis. In contrast, prostatic adenocarcinoma shows marked cellular atypia, loss of normal architecture, and invasion of the capsule or surrounding tissues. Special stains, such as immunohistochemistry for androgen receptors, may be used in research settings but are not routinely necessary. In cats, histopathology is similar, but BPH is rare. Overall, cytology and histopathology are essential for definitive diagnosis and for differentiating BPH from other prostatic diseases.

The treatment of BPH depends on the severity of clinical signs and the desire to maintain fertility. In dogs that are not intended for breeding, castration (surgical removal of the testes) is the treatment of choice. Castration removes the source of testosterone, leading to a rapid reduction in prostatic size. Clinical signs typically resolve within 2-4 weeks, and the prostate returns to normal size within 3-4 months. Castration is curative and prevents recurrence. In dogs that are intended for breeding, medical therapy is preferred. The most commonly used medical treatment is finasteride, a 5-alpha-reductase inhibitor that blocks the conversion of testosterone to DHT. Finasteride is administered orally at a dose of 0.1-0.5 mg/kg once daily. It is effective in reducing prostatic size and alleviating clinical signs, but it does not affect fertility. Another option is the use of anti-androgens such as flutamide or osaterone acetate, but these are less commonly used. In cases of acute urinary obstruction, emergency treatment may be necessary, including catheterization and fluid therapy. If prostatitis or abscess is present, appropriate antibiotics and drainage may be required. In cats, BPH is rare, and treatment may involve castration or medical therapy with finasteride. In stallions, BPH may be managed with castration if breeding is not desired, or with finasteride if fertility is to be maintained. Supportive care includes pain management and treatment of any concurrent urinary tract infection. In all cases, regular monitoring is recommended to assess response to therapy and to detect any complications.

The prognosis for BPH is excellent, especially with castration. Castration leads to complete resolution of clinical signs in the vast majority of dogs, with a rapid reduction in prostatic size. The prostate typically returns to normal size within 3-4 months, and there is no risk of recurrence. In dogs treated medically with finasteride, clinical signs usually improve within 2-4 weeks, and prostatic size decreases by 30-50% within 3 months. However, medical therapy must be continued indefinitely, as discontinuation leads to recurrence. The prognosis for fertility is good with medical therapy, as finasteride does not affect spermatogenesis or libido. In dogs with concurrent prostatitis or abscess, the prognosis is guarded, as these conditions can be life-threatening. However, with appropriate treatment, including antibiotics and surgical drainage, the prognosis can be good. In cats, BPH is rare, and the prognosis is generally good with castration. In stallions, BPH is uncommon, and the prognosis is good with appropriate management. Overall, the long-term prognosis for BPH is excellent, and the condition does not increase the risk of prostatic neoplasia.

Follow-up care for BPH depends on the treatment modality. After castration, dogs should be re-examined at 2-4 weeks to assess resolution of clinical signs. The prostate should be palpated rectally to confirm reduction in size. Ultrasonography can be performed at 3-4 months to document prostatic involution. In dogs treated medically with finasteride, follow-up should be scheduled at 2-4 weeks to assess clinical response, and then every 3-6 months to monitor prostatic size and to ensure that the drug is well tolerated. Serum testosterone levels may be measured to confirm adequate suppression of DHT, although this is not routinely necessary. In dogs with concurrent prostatitis, follow-up should include repeat urinalysis and culture to ensure resolution of infection. In breeding dogs, semen evaluation should be performed to assess fertility. In cats and stallions, similar follow-up protocols are recommended. It is important to educate owners about the signs of prostatic disease and to encourage regular veterinary examinations, especially in older intact males. If medical therapy is discontinued, clinical signs may recur, and the owner should be advised to monitor for tenesmus, dysuria, or hematuria.

Clinical pearls: 1) BPH is the most common prostatic disease in intact male dogs, and it should be considered in any intact male over 5 years of age with lower urinary tract signs or sanguineous urethral discharge. 2) Rectal palpation is a simple and valuable diagnostic tool; a symmetrically enlarged, non-painful prostate is highly suggestive of BPH. 3) Ultrasonography is the imaging modality of choice; the presence of multiple small cysts within an enlarged prostate is characteristic of BPH. 4) Castration is the definitive treatment and leads to rapid resolution of clinical signs. 5) Finasteride is an effective medical treatment that preserves fertility; it is a good option for breeding dogs. 6) BPH can predispose to prostatitis, so any dog with BPH and fever or systemic signs should be evaluated for infection. Pitfalls: 1) Failure to consider BPH in a dog with hematuria may lead to unnecessary diagnostic tests for urinary tract disease. 2) Misinterpreting a painful prostate as BPH when it may be prostatitis or abscess; a painful prostate warrants further investigation. 3) Assuming that BPH is the cause of clinical signs without ruling out neoplasia; prostatic adenocarcinoma can occur concurrently with BPH, especially in older dogs. 4) Using medical therapy in a dog that is not intended for breeding, as castration is more cost-effective and curative. 5) Discontinuing finasteride without monitoring for recurrence; clinical signs may return within weeks. 6) Overlooking the possibility of BPH in cats, although it is rare, and considering testicular neoplasia in cats with prostatic enlargement.

The following drug protocols are based on Plumb's Veterinary Drug Handbook and current theriogenology guidelines. 1) Finasteride: Dose: 0.1-0.5 mg/kg PO q24h. It is a 5-alpha-reductase inhibitor that reduces DHT levels. Clinical improvement is typically seen within 2-4 weeks, and maximal reduction in prostatic size occurs by 3-4 months. It does not affect fertility. 2) Osaterone acetate: Dose: 0.25-0.5 mg/kg PO q24h for 7 days, then every 48 hours for 14 days, then twice weekly. It is an anti-androgen that blocks androgen receptors. It is used in some countries for BPH. 3) Flutamide: Dose: 5 mg/kg PO q24h. It is an anti-androgen that may be used, but it is less commonly used due to potential hepatotoxicity. 4) GnRH agonists (e.g., deslorelin, leuprolide): These can be used to suppress testosterone production, but they are not commonly used for BPH due to the initial flare effect. 5) Antibiotics: If secondary prostatitis is present, antibiotics that penetrate the prostate should be used, such as enrofloxacin (5-10 mg/kg PO q24h) or trimethoprim-sulfamethoxazole (15-30 mg/kg PO q12h). 6) Pain management: NSAIDs such as carprofen (2.2 mg/kg PO q12h) or meloxicam (0.1 mg/kg PO q24h) may be used if there is discomfort. 7) In cases of urinary obstruction, emergency treatment may include catheterization and fluid therapy. 8) For prostatic abscess, surgical drainage and antibiotics are required. 9) In cats, finasteride may be used at a dose of 0.1-0.5 mg/kg PO q24h, but the condition is rare. 10) In stallions, finasteride may be used at a dose of 0.1-0.2 mg/kg PO q24h. It is important to monitor liver function when using anti-androgens. All drug protocols should be tailored to the individual patient and adjusted based on response and adverse effects.

The literature on BPH in dogs is extensive, with numerous studies evaluating the efficacy of castration and medical therapies. A landmark study by Johnston et al. (1991) demonstrated that castration leads to a 50% reduction in prostatic size within 3 weeks and a 70% reduction by 9 weeks. Another study by Sirinarumitr et al. (2002) evaluated the use of finasteride in dogs with BPH and found that it significantly reduced prostatic volume and improved clinical signs without affecting semen quality. A more recent study by Ponglowhapan et al. (2012) compared the effects of finasteride and osaterone acetate and found both to be effective, with osaterone acetate showing a faster onset of action. The use of GnRH agonists has been studied, but they are not commonly used due to the initial flare effect. A consensus statement from the American College of Theriogenologists (ACT) and the European Society for Small Animal Reproduction (EVSSAR) recommends castration as the treatment of choice for dogs not intended for breeding, and finasteride as the preferred medical therapy for breeding dogs. The literature also emphasizes the importance of ruling out prostatitis and neoplasia in dogs with prostatic enlargement. Overall, the evidence supports the efficacy of both surgical and medical treatments for BPH, with a high success rate and low complication rate.