Pathogenesis of Benign Prostatic Hypertrophy

The pathogenesis of BPH is not known completely. Testosterone, DHT, estradiol, and some growth factors such as epidermal growth factor, transforming growth factor, keratinocyte growth factor, and basic growth factor are involved in prostatic growth. DHT, a form of testosterone metabolized by 5α-reductase enzyme, is a major hormone involved in prostatic enlargement; it enhances growth of stromal and glandular components. The uptake of DHT by prostatic cells is stimulated by estradiol. Prostatic DHT concentration in dogs with BPH was reported to be approximately two to four times greater than in normal intact male dogs. However, plasma and prostatic testosterone concentration of dogs with BPH were in the normal range.

Diagnosis of Benign Prostatic Hypertrophy

The diagnosis of BPH is based on clinical signs and a detection of prostate enlargement without any other prostatic diseases. Some affected dogs may be diagnosed after blood contamination is found in semen during routine breeding soundness examination without any other clinical signs. In the dog BPH may be suspected based on clinical signs including constipation, sanguineous discharge dripping from the tip of the penis, blood in the urine or semen, and difficult urination. Straining to defecate may result in perineal hernias. Scottish terriers may have more severe clinical signs of BPH than in other breeds. Digital rectal examination reveals a symmetrically large, smooth surface and firm prostate with no sign of pain during examination. A dog with BPH and a large intraprostatic cyst may have an asymmetric prostatic lobe. The complete blood count in dogs with BPH is usually normal.

Prostatic enlargement is diagnosed radiographically when the prostatic diameter on the lateral radiograph exceeds 70% of the distance between the sacral promontory and the pubis. Ultrasonographically the prostate gland usually is enlarged symmetrically with parenchyma that is homogeneous in echogenicity and either with or without cavitating cystic lesions. A prostatic cyst is usually visible as a discrete, hypoechoic lesion within the parenchyma. The volume of prostatic tissue (cm³) can be calculated using the following formula:

where L = the greatest craniocaudal length, W = the transverse dimension, and D = the dorsoventral length of the prostate measured in centimeters (Kamolpatana, Johnston, and Johnston, 2000). Prostatic volume in the dog with BPH is usually greater than 10 ml, which is generally 2 to 6.5 times greater than that of normal dogs of similar weight.

Prostatic fluid collected by ejaculation, prostatic massage, or prostatic aspiration (ultrasound guided) in the dog with BPH should yield less than 10⁴ colony-forming units (CFUs) of aerobic bacteria per milliliter and no anaerobic bacteria, Mycoplasma spp., or Ureaplasma spp. Normal seminal fluid sediment cytology lacks inflammatory cells containing less than 3 white blood cells (WBC)/hpf. Sometimes diagnosis of squamous metaplasia of the prostate is possible if the seminal fluid has an abundance of squamous cells in the sediment cytology.

Medical Treatment of Benign Prostatic Hypertrophy

The treatment objectives in dogs with BPH are to decrease the size of the prostate gland and to alleviate signs related to BPH. Castration is a permanent BPH treatment and is recommended for most dogs with BPH. Medical management using hormone therapy is an alternative to castration for BPH in cases in which the risk of anesthesia or surgery is high. However, hormone therapy is only a temporary treatment for BPH. For breeding dogs, medical treatment is necessary.

Finasteride (Proscar) 5-mg tablet, at a dosage of 0.1 to 0.5 mg/kg (or 1 tablet/dog weighing between 1 and 50 kg) q24h PO is recommended for medical BPH treatment in dogs. Finasteride is a 5α-reductase inhibitor that blocks production of DHT from testosterone. The prostate in dogs with BPH treated with finasteride involutes by programmed cell death (apoptosis) rather than necrosis; thus no inflammatory process is associated. Finasteride significantly decreases prostatic volume and serum DHT concentration by 40% to 50% but does not affect adversely semen quality, libido, or serum testosterone in dogs with BPH. The only effect of finasteride on semen quality is a decrease in semen volume. Clinical signs related to BPH, such as constipation or blood in the semen, abate within 1 to 4 weeks after the onset of finasteride treatment. No adverse effects have been reported using finasteride. During and after finasteride treatment, dogs with BPH have bred bitches successfully that subsequently underwent normal pregnancy, gestation duration, and litter size. Dogs with BPH should receive finasteride treatment for 1 to 4 months. Prostate size and clinical signs are decreased significantly at the end of 1 month of treatment in most dogs. About 45% of treated dogs showed recurrence of BPH clinical signs within 4 months after cessation of treatment with finasteride using a dose of 0.1 to 0.5 mg/kg for 4 months. Finasteride had no adverse effect on complete blood count or serum biochemistry during and after the 4 months of therapy. Deslorelin (Suprelorin), a synthetic gonadotropin-releasing hormone (GnRH) analog, has been used for BPH treatment in dogs (Limmanont, Phawaphutanont, and Sirinarumitr, 2011). Suprelorin is available as a 4.7 or 9.4 mg deslorelin acetate for subcutaneous implantation and can last for 6 months or 12 months, respectively. Prostatic size and seminal fluid volume are decreased during the 6-month treatment period after administration of 4.7 mg of deslorelin. Within 4 months of deslorelin implantation, anejaculation (inability to ejaculate) was reported in all treated dogs. After 4 months from hormone cessation (10 months after implant administration), all treated dogs still had anejaculation, no recurrence of BPH clinical signs, and small prostatic sizes. No skin reaction at the implantation site (between the shoulder blades) was detectable, and there were no adverse effects on complete blood or serum biochemistry during and after the 4 months of treatment. However, deslorelin implantation for BPH treatment is not recommended for stud dogs because of the actions of decrease in testicular sizes and testosterone levels, resulting in poor semen quality and anejaculation. It is unknown how long normal testicular function remains impaired after deslorelin treatment in male dogs.

Other medical treatments used to reduce prostatic size in BPH dogs include diethylstilbestrol (0.2 to 1 mg/dog q48-72h for 3 to 4 weeks PO), medroxyprogesterone acetate (3 mg/kg [with a minimum dose of 50 mg] SC given at least 4 weeks apart), megestrol acetate (0.55 mg/kg q24h PO for up to 4 weeks), and flutamide (5 mg/kg q24h PO). The potential side effects of estrogen treatment in dogs include bone marrow suppression with resultant anemia, thrombocytopenia, or pancytopenia. Repeated estrogen treatments may incite growth of fibromuscular stroma and induce squamous metaplasia of the prostate. Adverse effects of medroxyprogesterone acetate treatment in dogs include increased appetite, hypothyroidism, diabetes mellitus, testicular degeneration, and decreased serum concentration of testosterone. Flutamide significantly decreased prostate size within 10 days of treatment. Libido and sperm production were unchanged in male dogs treated with flutamide for 1 year; however, a course of flutamide treatment is prohibitively expensive.