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Prostatic hyperplasia/cystic hyperplasia in the dog

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Category: Schede
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  • Disciplina: Urologia
  • Specie: Cane

Almost all sexually intact male dogs over 6 years old develop a prostatic disease defined prostatic hyperplasia.1 This disorder can, in fact, be detected histologically already from 2.5 years old. Cystic hyperplasia appears later, at about 4 years of age. Cats are not affected by this disorder: the only two species susceptible are dogs and humans.2

 

PATHOGENESIS

The underlying cause of prostatic hyperplasia is an imbalance in the ratio of androgens/oestrogens: in fact, with increasing age the concentration of testosterone in the plasma tends to decrease, while that of oestrogens remains the same, leading to a decrease in the ratio.2

This causes an increase in the expression of androgen receptors in the prostate. Dihydrotestosterone is the predominant hormonal mediator.3,4 Prostatic hyperplasia consists in an increase in both the number and size of cells, although the increase in the number is predominant. These two factors lead to enlargement, usually symmetrical and bilateral, of the gland. Furthermore, the hyperplastic gland is more vascularised and has a greater tendency to bleed.

Not uncommonly affected animals develop cysts which may or may not communicate with the lumen of the urethra through the prostatic ducts. These cysts may be of different sizes and usually contain a clear fluid which ranges in colour from transparent to amber-reddish. Although the size of the gland increases, its secretory capacity decreases leading to a reduction in the volume of seminal fluid.

 

CLINICAL FEATURES

This pathology affects up to 100% of sexually intact male dogs, starting from 2.5 years old, and is often asymptomatic. The most common clinical signs in those dogs which do have manifestations are a bloody urethral discharge that is independent of micturition, haematuria, haematospermia and urinary or rectal tenesmus. Prostatic hyperplasia is rarely accompanied by systemic symptoms: affected dogs are usually lively and active, although occasional cases of anorexia, lethargy and pain have been reported.5,6  At trans-rectal palpation the prostate is bilaterally enlarged, mobile, not tender and of variable consistency. Rarely the gland may be enlarged asymmetrically.6,7  Ultrasound examination reveals that the prostate is diffusely hyperechoic with intraparenchymal hypoechoic cavities (Figs. 1 and 2). These cavities are well defined and have smooth outlines.

 

DIAGNOSIS

The definitive diagnosis can only be made from examination of a biopsy specimen; however, it is not necessary to carry out this examination if the signalment, history and clinical findings are typical. A positive response to treatment (whether pharmacological or surgical) confirms the diagnosis.

Finally, it should not be forgotten that benign prostatic hyperplasia in the adult/elderly dog can be accompanied by other pathological conditions: for this reason it can easily mask a neoplasm in its early stages or chronic prostatitis. It is, therefore, important to remember that prostate cancers do not respond to the treatment for hyperplasia and that chronic prostatitis leads to the development of infections of the lower urinary tract and alterations to the prostatic fluid.

 

TREATMENT

Treatment is imperative only in symptomatic subjects. There are currently two therapeutic options, one conservative (pharmacological treatment) and one surgical. Conservative treatment can also be used while waiting to perform the definitive surgery.

Conservative or pharmacological treatment. Oestrogen, anti-androgens or progestins may be used:

1.     Oestrogens: these have a negative feed-back effect on the production of pituitary gonadotropins which is reflected by decreased synthesis of androgens. A brief course of treatment is able to reduce the secretory capacity of the prostate for months. The most effective doses have not yet been determined and a therapeutic protocol has not been defined. It is important to remember that oestrogen toxicity can be fatal following overdoses, repeated administrations or, more rarely, idiosyncratic phenomena.8-11 Initially the toxicity is manifested by a leucocytosis characterized by a left shift followed by severe bone marrow suppression resulting in anaemia, thrombocytopenia and leucopenia. Repeated administrations of oestrogens can also cause squamous metaplasia of the prostate and stasis of secretions.

2.     Anti-androgens:

1. Flutamide: this is a non-steroidal anti-androgen that, administered orally, competes with the receptors for dihydrotestosterone within the prostate gland. In dogs it causes a significant decrease in the size of the gland within 10 days. The hyperplasia recurs within 2 months of suspending treatment with the drug. Following treatment with a dose of 5 mg/kg/die for 1 year, no dogs showed a decrease in libido or in the production of sperm.

2. Finasteride: this is an inhibitor of alpha-5-reductase. At a dose of 0.1-0.5 mg/kg/die it lowers serum dehydrotestosterone levels and is able to reduce the volume of the prostate by about 40% after 8 weeks.12. It reduces the amount of semen produced (reducing the volume of prostatic fluid), without, however, damaging its quality; furthermore, libido and fertility are not altered.13 This drug can cause anomalies in male foetuses when these are exposed to the drug at 3 months of gestation and for this reason is a risk to pregnant women. The tablets are covered, to prevent contact with the active ingredient while handling the drug, although this will be present in the semen, urine and faeces of treated dogs.

3.     Progestins:

1. Megestrol: this causes a reduction in the concentration of testosterone in the serum, inhibits binding of dihydrotestosterone to its receptors as well as lowering the concentration of this latter; furthermore it decreases the number of androgen receptors in the prostate.14At the dose of  0.55 mg/kg/die for 4 weeks it resolves clinical signs without harming sperm production.

2. Medroxyprogesterone acetate: this was given subcutaneously at a dose of 3 mg/kg and the treated animals evaluated for 27 weeks. The clinical signs of prostatic hyperplasia reappeared 10-24 months after the treatment. Throughout the 27 weeks of evaluation the quality of the semen was not altered. Data on the long-term repeated use of this drug are lacking.

3. Delmadinone acetate: this drug is not marketed in Italy but is available in the United Kingdom in the form of an injectable solution authorised for the treatment of prostatic hyperplasia. The recommended dose is 1-2 mg/kg i.m. or s.c. In those animals that respond positively to the first dose, the injection is repeated every 3-4 weeks.

Surgical treatment. Castration is the treatment of choice15in that it causes a 75% reduction in the volume of the prostate in 8-9 weeks16 and there is no equally effective medical therapy. The involution of the gland starts a few days after the intervention and is about 50% by 3 weeks after the operation; the urethral discharge generally resolves within 4 weeks. Prostatic cysts can be treated by ultrasound-guided fine needle aspiration: in this case the aspirated fluid should be sent to the laboratory for microbiological studies.

 

MONITORING THE PATIENT

In the case of asymptomatic subjects the owner should be informed about the characteristic clinical signs in order that these can be noted early if they occur. In patients treated conservatively or surgically, trans-rectal palpation of the prostate should be carried out every 2-3 weeks to check that the involution of the gland is proceeding as expected. If the involution is not sufficient, the presence of other unidentified, concomitant prostate disorders should be considered.

 

Suggested readings

  1. Ettinger SJ, Feldman EC: “Textbook of Veterinary Internal Medicine, 6th edn”. Elsevier-Saunders, St. Louis 2005.
  2. Couto CG, Nelson WR: “Medicina interna del cane e del gatto”Elservier-Masson, 2010.
  3. BSAVA Manual of Canine and Feline Nephrology and Urology Second edition, Edited by Johnathan Elliot and Gregory F. Grauer, 2007.
  4. OsborneCA, Finco DR: Canine and feline nephrology and urology. Williams & Wilkins, Philadelphia, 1995

 

References

  1. Berry SJ, Strandberg JD, Saunders WJ, Coffey DS.: “Development of canine benign prostatic hyperplasia with age.” Prostate. 1986;9(4):363-73.
  2. Wilson JD.: “The pathogenesis of benign prostatic hyperplasia”Am J Med. 1980 May;68(5):745-56.
  3. Isaacs JT, Coffey DS.: “Changes in dihydrotestosterone metabolism associated with the development of canine benign prostatic hyperplasia.” Endocrinology. 1981 Feb;108(2):445-53.
  4. Wenderoth UK, George FW, Wilson JD.: “The effect of a 5 alpha-reductase inhibitor on androgen-mediated growth of the dog prostate.” Endocrinology. 1983 Aug;113(2):569-73.
  5. Krawiec DR, Heflin D.:”Study of prostatic disease in dogs: 177 cases (1981-1986). J Am Vet Med Assoc. 1992 Apr 15;200(8):1119-22.
  6. Root Kustritz M, Merkel L.: “Theriogenology question of the month. Benign prostatic hypertrophy (BPH), prostatitis, and prostatic neoplasia.” J Am Vet Med Assoc. 1998 Sep 15;213(6):807-9.
  7. GilsonSD, Miller RT, Hardie EM, Spaulding KA.: “Unusual prostatic mass in a dog.” J Am Vet Med Assoc. 1992 Mar 1;200(5):702-4.
  8. Fogle B.: “Iatrogenic oestrogen poisoning in a Maltese terrier” Vet Rec. 1981 Sep 5;109(10):201.
  9. Mills JN, Slatter DH.: “Stilboestrol toxicity in a dog” Aust Vet J. 1981 Jan;57(1):39-42.
  10. Rhodes L, Ding VD, Kemp RK et al.: “Estradiol causes a dose-dependent stimulation of prostate growth in castrated beagle dogs.” Prostate. 2000 Jun 15;44(1):8-18.
  11. Sontas HB, Dokuzeylu B, Turna O, Ekici H. : “Estrogen-induced myelotoxicity in dogs: A review.” Can Vet J. 2009 Oct;50(10):1054-8.
  12. Sirinarumitr K, Sirinarumitr T, Johnstone SD, Sarkar DK, Kustritz MV.: “Finasteride-induced prostatic involution by apoptosis in dogs with benign prostatic hypertrophy”.Am J Vet Res. 2002 Apr;63(4):495-8.
  13. Sirinarumitr K, Johnston SD et al.: “Effects of finasteride on size of the prostate gland and semen quality in dogs with benign prostatic hypertrophy.”J Am Vet Med Assoc. 2001 Apr 15;218(8):1275-80.
  14. Geller J, Albert J, Geller S. et al.: “Effect of megestrol acetate (Megace) on steroid metabolism and steroid-protein binding in the human prostate.”J Clin Endocrinol Metab. 1976 Nov;43(5):1000-8
  15. Huggins C.: “The etiology of benign prostatic hypertrophy.” Bull N Y Acad Med. 1947 Dec;23(12):696-704.
  16. Berry SJ, Cofffey DS, Strandber JD, Ewing LL.: “Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostati hyperplasia.” Prostate. 1986;9(3):295-302.