Prostatic disease in the dog (Proceedings)

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Prostatic disease in the dog (Proceedings)

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Nov 01, 2010

Benign Prostatic Hyperplasia

The most common prostatic disease in the dog is benign prostatic hyperplasia (BPH), which occurs in intact male dogs that are usually ≥ 2 years-of-age. Scottish terriers appear to be more severely affected than other dog breeds. The etiology is associated with altered androgen-estrogen ratios as the dog matures. Dogs with BPH can be asymptomatic or display clinical signs such as tenesmus (staining to defecate), hemorrhagic or clear urethral discharge, and hematuria. On prostatic palpation abdominally or rectally the prostate is nonpainful and often symmetrically enlarged. The presence of BPH predisposes the affected patient to developing prostatic cysts and bacterial prostatitis, which may produce additional clinical signs associated with those disorders. Data base results usually reveal an unremarkable CBC and biochemistry profile with a urinalysis indicating hematuria. Survey radiographs generally reveal prostatic enlargement, while abdominal ultrasonography indicates that the prostate has either normal echogenicity or is diffusely hyperechoic with small parenchymal cavities. Fluid obtained post-prostatic massage or semen post-ejaculation may be normal or have RBCs present.

Castration is the most effective treatment of BPH. Although treatment is only necessary if clinical signs are present, asymptomatic patients can still benefit from castration in regard to preventing the development of clinical signs. Involution of the gland begins shortly after orchiectomy is performed, reaching approximately 50% reduction in size by 3 weeks post-castration. If the patient with BPH is symptomatic but the owner rejects castration as a therapeutic option, medical intervention can be considered.

Hormonal therapy has long been recognized as a means to achieve reduction in the size of the enlarged prostate, but has many potential side effects. In addition, the hormones generally used in treatment affect the reproductive potential of the patient, limiting the usefulness of hormonal therapy in affected dogs that are kept intact for breeding purposes.

Estrogen depresses pituitary gonadotrophin secretion, reducing testicular androgen secretion which ultimately results in prostatic atrophy. Products used in BPH therapy include diethylstilbesterol (DES) administered at 0.2 – 1 mg PO q2 – 3 days for 3 - 4 weeks and Premarin, a conjugated estrogen product, administered at 0.312 – 0.625 mg/day PO for 5 days and then every 2 – 4 days for 3 weeks initially. A maintenance dose can then be established to control the dog's clinical signs over a longer period of time, if needed. Potential side effects from estrogen include bone marrow suppression (anemia, leucopenia, and thrombocytopenia), which can be permanent or require lengthy support for recovery. Paradoxically, use of estrogen products can eventually result in prostatic enlargement due to the induction of prostatic metaplasia, alterations in secretory status, and fibromuscular growth. These estrogen-induced changes can also predispose the patient to development of prostatic cyst formation and bacterial infection. In addition, reduction in the patient's libido can result from the administration of estrogen. Due to the many potentially undesirable side effects, estrogen therapy for BPH is not recommended.

Progestogens have also been used in the treatment of BPH, including megestrol acetate (0.5 mg/kg/day PO for 4 – 8 weeks) and medroxyprogesterone acetate (3mg/kg subQ). These progestogens decrease the number of prostatic androgen receptors and testosterone levels, competitively inhibits binding of dihydrotestosterone (DHT) to intracellular receptors, and inhibits 5-α-reductase, resulting in decreased DHT concentrations. As a consequence, decreased libido and fertility may develop. Several adverse effects may occur with the use of megestrol, including weight gain, lethargy, behavioral changes, mammary enlargement, diabetes mellitus, neoplasia, and adrenal suppression. Medroxyprogesterone acetate decreases testosterone levels and temporarily inhibits spermatogenesis. Many of the same adverse effects seen with megestrol can also be seen with medroxyprogesterone. Although some dogs with BPH receiving progestogens have been successfully bred, the adverse effects associated with these drugs make them undesirable for long-term therapy.

Finasteride and flutamide have been used successfully for the treatment of BPH in dogs. However, it should be remembered that both of these agents are expensive and must be given on a maintenance basis to sustain reduction in the size of the hyperplastic prostate.

Finasteride (Proscar®) is a 5-alpha reductase inhibitor which blocks conversion of testosterone to its active metabolite, dihydrotestosterone. The dose is 0.1 - 1 mg/kg PO daily for 1 – 4 months. Finasteride does not affect serum testosterone levels and has little effect on libido although it will decrease the prostatic portion of ejaculate. Clinical signs related to BPH generally begin to resolve approximately one week after the initiation of finasteride therapy and are often completely resolved within one month post-initiation. Once therapy with finasteride has been discontinued, the prostate will once again hypertrophy, reaching its pre-treatment size approximately 1 – 2 months after completion of finasteride administration. The drug is teratogenic and should not be administered by women of reproductive age. If used in dogs intended for breeding, it is recommended to discontinue use of finasteride temporarily 10 days prior to breeding and during the breeding period in order to minimize any risk to puppies produced and to restore the volume of prostatic fluid in the ejaculate.

Flutamide (Eulexin®) is an antiandrogenic agent that competes for dihydrotestosterone receptors in the prostate. The dose is 2.5 – 5 mg/kg/day PO for 4 – 6 weeks. Flutamide has few effects on testicular function, causing no change in the patient's libido, sperm production, or apparent fertility. However, hepatopathy as severe as liver failure has been documented in humans taking flutamide.

Chemical castration with subsequent resolution of BPH can be accomplished with the gonadotropin-releasing hormone (GnRH) agonists deslorelin (Suprelorin®) and nafarelin (Gonazon®) or the synthetic testosterone analogue osaterone acetate (Ypozone®). The GnRH agonists are used as subQ sustained release implants, achieving down regulation of GnRH receptors and subsequent suppression of testosterone an estradiol concentrations. The implants result in decreased size of both the prostate and testes of the patient for a period of 6 – 12 months. The patient is rendered infertile until the implant is removed. In contrast, osaterone acetate (0.25 – 0.5 mg/kg PO daily for 7 days), which has been marketed in Europe for treatment of BPH, competitively inhibits prostatic DHT receptors, resulting in decreased prostatic size and resolution of clinical signs without affecting sperm quality or the patient's fertility. Notable reduction in clinical signs occurs within two weeks of completion of administration and reduction in prostatic size is maintained for approximately 6 months. Potential adverse effects of osaterone include reduction in serum cortisol and adrenocortical insufficiency.