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BENIGN PROSTATE HYPERPLASIA

Author : Henry L’Eplattenier

Categories : Vets

Date : April 4, 2011

Henry L’Eplattenier considers this common condition in older dogs and discusses its symptoms and treatment

THE prostate is the only major accessory sex gland in the dog. It is a bilobed structure that completely encircles the proximal portion of the urethra.

In young animals, the prostate lies entirely within the pelvic cavity, but with sexual maturity it increases in size and assumes an abdominal position.

Histologically, the prostate has an epithelial and a stromal component. The epithelial cells form tubuloalveoli that drain into the urethra. The prostate is surrounded by a capsule containing smooth muscle fibres that extend into the organ, dividing the alveolar tissue into dis tinct lobules.

Blood supply to the prostate is supplied by the prostatic artery, which arises from the pudendal or umbilical artery. Anastomoses can be found between the prostatic vessels and the urethral artery, and the cranial and caudal rectal artery. Venous blood returns via the prostatic vein to the internal iliac vein. Lymph drains into the iliac lymph nodes.

Sympathetic innervation is provided by the hypogastric nerve, which stimulates the active secretory process and expulsion of secretions by smooth muscle contractions.

Parasympathetic innervation with fibres from the pelvic nerve also contributes to smooth muscle contraction1.

1 / 5 Fluid secreted by the prostate forms more than 90 per cent of the total volume of the ejaculate2 and is expulsed in the first and third fractions of the ejaculate.

Its main functions are to reduce the viscosity of the ejaculate and to facilitate sperm transport. Prostatic secretions are acidic and have a bactericidal effect, which may prevent ascending urinary tract infections.

With increasing age, and under the influence of androgens, the prostate undergoes spontaneous enlargement, referred to as benign prostatic hyperplasia (BPH).

Pathogenesis of BPH

BPH occurs commonly in older dogs. After five years of age, nearly all dogs have a degree of BPH, which may continue to develop with increasing age.

Two forms of BPH may be distinguished – glandular hyperplasia and complex hyperplasia (or cystic hyperplasia).

In benign glandular hyperplasia an increase in the amount of secretory epithelium occurs. Each of the lobules is larger and has more elaborate branching than found in the normal gland. The alveoli are larger and contain more cells. The amount of stroma is relatively less than in the normal gland.

In the complex form of BPH, a variety of changes occur within the affected gland, including glandular hyperplasia, atrophic or attenuated secretory epithelium, and usually cysts or dilated alveoli. Hyperplasia can begin as early as one or two years of age and its prevalence increases with age.

It has long been recognised that hormones are involved in the induction of benign prostate hyperplasia. However, the exact aetiology of BPH is not understood. BPH develops only in intact males and is age-related. There is a moderate decline of circulating testosterone and dihydrotestosterone (DHT) concentration throughout adult life, while the serum estradiol level is unchanged. Therefore, it is thought that variations in the ratio of circulating androgens (testosterone and DHT) and oestrogens with increasing age may induce the morphological changes associated with BPH3.

The parenchymal changes associated with BPH can predispose the prostate to develop other conditions, such as suppurative prostatitis and/or prostatic abscess, and prostatic cysts.

Clinical signs and diagnosis of BPH

In most cases, BPH does not cause any clinical signs. Only if the prostate is so enlarged that it compresses the colon and interferes with defaecation are dogs usually presented to the

2 / 5 veterinarian. The owner may describe ribbon-shaped or flattened faeces. Other clinical signs frequently include haemorrhagic discharge from the urethra.

A physical examination should include abdominal and rectal palpation. Both testicles should be palpated for tumours. On rectal examination, the prostate is found to be enlarged, symmetrical and painless. In larger dogs, elevating the contents of the abdomen caudodorsally with one hand during rectal exam may facilitate the palpation of the prostate.

Ultrasound examination usually reveals a symmetrically enlarged prostate with loss of the normal homogenous appearance (Figure 1). Ultrasonography is also excellent in determining the presence of anechoic (fluid-filled) cysts within the prostatic parenchyma.

A definitive diagnosis can be obtained by cytological exam of prostatic cells4 obtained through fine needle aspirates (Figure 2).

Routine haematology and biochemistry do not normally show any changes specific for BPH.

More recently the serum concentration of canine prostatespecific arginine esterase (CPSE) has been shown to be an excellent indicator of BPH in the dog (Odelis CPSE test).

CPSE is a hormone secreted by prostatic epithelial cells under the control of sex hormones. The protein belongs to the family of kallikreins, as does prostatespecific antigen (PSA) in man.

CPSE is present in sperm (comprising more than 90 per cent of the protein in prostatic fluid) and in blood. When prostatic cells become hyperplastic, the serum concentration of CPSE increases.

Treatment of BPH

Treatment is required in patients with clinical signs of prostatic disease. The goal is to decrease the size of the prostate and alleviate the signs of pelvic canal obstruction.

The treatment of choice is surgical castration. A 50 per cent reduction of the size of the prostate can be expected within three weeks. Alternatively, chemical castration is possible1. A variety of pharmaceutical agents have been tested in dogs and these can be divided into three groups:

• progestogens;

• 5-alpha-reductase inhibitors; and

• anti-androgens.

Progestogens act by feedback on the hypothalamus and pituitary glands and indirectly reduce

3 / 5 testosterone production by the testes. They do not only affect the prostate, but also have an influence on the dog’s behaviour (reduced aggressiveness, decreased libido).

Progestogens include delmadinone acetate (1mg/kg to 2mg/ kg SQ, repeated after eight days if no response), medroxyprogesterone acetate (3mg/kg SQ twice at four weeks interval) and megestrol acetate (0.55mg/kg PO for four weeks).

Circulating testosterone enters the prostatic cells and is transformed into DHT. DHT is the androgen that controls the growth of prostatic cells. The enzyme responsible for this transformation is called 5-alpha-reductase.

Inhibition of this enzyme, therefore, blocks the effect of androgens on the prostate without suppressing the other systemic effects of circulating testosterone (behaviour and libido). Synthetic steroid finasteride is a 5-alpha-reductase inhibitor, which is used effectively for treating BPH in humans, and has also successfully been used to induce prostate atrophy in dogs without decreasing sperm quality or libido (finasteride, 5mg per dog between 10kg and 50kg every 24 hours).

More recently osaterone acetate has been licensed for the treatment of BPH in dogs. It is an anti- androgen, which blocks the uptake of testosterone by prostate cells and blocks the androgen receptor in the cell, thereby inhibiting the binding of DHT to the receptor. It therefore has a rapid onset of action. It is given at a dose of 0.25mg/kg to 0.5 mg/ kg SID for seven days and has an effect for about six months.

As with the 5-alpha-reductase inhibitors, the level of circulating testosterone is not changed, so that sperm quality and libido are not influenced. Osaterone acetate is, therefore, indicated instead of surgical castration in breeding dogs with BPH. Due to its rapid onset of action (quicker than surgical castration), osaterone acetate can also be administered at the same time as surgical castration to accelerate reduction in size of the prostate.

References

1. Basinger R R, Robinette C L and Spaulding K A (2003). The prostate. In Slatter D (ed), Textbook of Small Animal Surgery (3rd edn), W B Saunders, Philadelphia: 1,542-1,557. 2. Johnston S D, Kamolpatana K, Root-Kustritz M V and Johnston G R (2000). Prostatic disorders in the dog, Anim Reprod Sci 60-61: 405-415. 3. Mahapokai W S (2000). Hormonally-Induced Benign Prostatic Hyperplasia in the Dog. Thesis. University of Utrecht. 4. Teske E and Nickel R (1996). Zur aussagekraft der zytologie bei der diagnostik des prostata-karzinoms beim hund, Kleintierpraxis 41: 239-247.

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