Download Introduction Canine prostatic diseases include benign prostatic hyperplasia (BPH), prostatitis (acute... Prostate disease in the dog

Prostate disease in the dog
Introduction
Canine prostatic diseases include benign prostatic hyperplasia (BPH), prostatitis (acute and chronic), prostatic
cysts, and prostatic neoplasia. These diseases may occur concurrently or separately. A complete history and
appropriate diagnostics are necessary to make an accurate diagnosis. This paper will discuss the signalment,
history, clinical signs, diagnostic tools, treatments and prognosis for each causes of prostate disease in the
canine.
Prostate anatomy
The prostate is a bi-lobed, oval to round, organ located within the cranial pelvic canal/caudal abdomen. The
proximal urethra runs through the center of both lobes. Testosterone is converted to dihydrotestosterone
(DHT) via the enzyme 5α-reductase. DHT stimulates prostatic development, growth and production of
glandular secretions. 5α-reductase is found in two distinct isoenzymes (types 1 and 2). Isoenzyme 1 is found in
the skin, liver and prostate; while isoenzyme 2 is found only in the prostate and other genital tissues.
Testosterone and DHT bind to the same androgen receptors and cause the same tissue effects. DHT binds
much more tightly and longer to the androgen receptors than testosterone; thus smaller amounts of DHT will
cause an amplified response by the prostate compared to testosterone.
Benign Prostatic hyperplasia
BPH is the most common disease of the prostate in intact male dogs. Approximately 50% of dogs 5 years of age
have some signs of BPH and by 7 years of age, 90% of intact dogs will have signs of BPH. This disease develops
directly due to the effect of testosterone on the prostate. Testosterone causes both hyperplasia and
hypertrophy. The prostate is highly vascularized with BPH, particularly in the periurethral zone, predisposing
to vascular fragility and bleeding from these vessels into the secretory ducts or into retention cysts. The
prostate will be symmetrical, non-painful and enlarged.
Most dogs with BPH have no clinical signs at all, but when signs develop, they may include sanguinous (fresh or
digested) drippings from the penis/prepuce, hematuria, hemospermia, stranguria, dysuria, incontinence,
and/or tenesmus. The degree of urinary or fecal signs is directly proportional to the increased size of the
gland. Some dogs may present with infertility due to alterations in prostatic fluid pH and osmolarity.
Rectal palpation may be accomplished in some dogs depending on their size and the location of the gland
within the pelvic canal. Upward pressure on the caudal abdomen may push the gland back into the pelvic canal
to facilitate palpation. Care should be taken making any assessment of prostate size unless the entire gland
can be palpated. Diagnosis may be accomplished with ultrasonography, prostatic fluid cytology, and/or
prostatic cytology or biopsy. Ultrasound usually reveals an enlarged, symmetrical gland with a homogenous
but hyperechoic (to normal) echotexture, with or without small-large retention cysts. In dogs with concurrent
prostatitis, the echotexture may be mottled, yet hyperechoic to normal. Prostatic fluid may be obtained via
prostatic massage for cytology. Cytologic specimens may also be obtained by fine needle aspirate (FNA) or
core biopsy. Semen collection can also be used to obtain 3rd fraction fluid which may contain light blood
contamination to frank hemorrhage or digested blood (coffee colored secretions).
Treatment of BPH involves removing the androgen exposure to the prostate. The most effective and fastest
way to treat is via castration. The prostate will be 80% smaller within 3 months of castration. However, in
breeding males, this is not an option. For these individuals, there are a number of medications that can be
used.
5α-reductase inhibitors. Finasteride is an azasteroid which blocks conversion of testosterone to DHT by
inhibiting the action of 5α-reductase type 2. Since testicular testosterone production is unaffected there are no
negative effects on libido, erection or spermatogenesis. Without the effect of DHT on the prostate, apoptosis
occurs resulting in reduction in prostate size. There is a very wide safety margin for this drug. The dose range
is 0.1 – 0.5 mg/kg po qd. The tablets come in 1 or 5 mg sizes so most medium – giant breed dogs would start at
5 mg/day and small/toy breeds would start at 1 mg/day. Some giant breed dogs may require 7.5 mg daily, but
most will respond well to the 5 mg/day dose. Care should be taken to avoid inadvertent ingestion of tablets
by pregnant bitches as teratogenic effects have been reported in women and rodents taking finasteride. There
is no concern over embryotoxicity or bitch fertility when breeding to a male on an active finasteride program.
Finasteride should be used continuously until the dog is neutered regardless of active breeding status.
Use of 5α-reductase inhibitors results in decrease secretion from the prostate, particularly the 3rd fraction. In
natural mating situations, the third fraction is an important factor in sperm transport, in that it provides a fluid
medium for sperm to swim up the cervix and into the uterus. Dogs on daily finasteride may have markedly
reduced amounts of fraction 3. It is possible that this may impact their fertility in a natural mating. Thus, once
a normal prostatic size is reached, some type of alternate dosing schedule is usually used (every other to every
third day treatment, or month on/month off regimen). This dosing schedule must be tailored to the individual
dog as some are more sensitive to the effects than others – this may actually have more to do with the size of
the dog and the dose he is on rather than individual response to medication.
Anti-androgen therapy. Osaterone acetate (Ypozane®, Virbac) is a testosterone analogue that competitively
binds to androgen receptors, reduces 5α-reductase concentrations, and inhibits testosterone transport into
prostatic cells. The dose is 0.25 - 0.5 mg/kg po qd once daily for 7 days. Treatment lasts for about 5 months.
This results in about 40% reduction in prostate volume within 14 days. Fifty percent of dogs have resolution of
clinical signs within 2 weeks and eighty-five percent have resolution within 6 months. There are no obvious
negative effects on semen quality or fertility. This medication is not labeled for use in the US.
Delmadinone acetate (Tardak®, Pfizer Animal Health) is a potent progestin that binds competitively to
androgen receptors and suppresses luteinizing hormone (LH) via negative feedback, which in turn decreases
circulating testosterone concentrations. There may be effects on fertility and libido so this is not a good
choice for actively breeding males. There is also a decrease in cortisol, which may lead to hypoadrenocorticism
in some patients. Diabetes mellitus may be exacerbated with this medication. One or two injections (1 - 2
mg/kg IM or SQ) at 14 days intervals is usually used, and results in remission of clinical signs in 50% of dogs
within 14 days and 85% by 6 months, with an almost 30% reduction in prostate volume within 14 days. This
medication is not labeled for use in the US.
Historically, medroxyprogesterone acetate has been used to reduce clinical signs, but it does not significantly
reduce prostate volume. It may also cause development of diabetes mellitus or mammary neoplasia, so its use
is not currently recommended. Megestrol acetate at 0.55 mg/kg orally once daily for 6-8 weeks has also been
used. Decreased libido and semen parameters may occur while the medication is being administered but
should return to pre-treatment values within a few months of discontinuing.
Antiestrogen therapy. Estrogens are believed to potentially cause BPH or to at least have a permissive role in
its development. Therefore, antiestrogens can be used to successfully treat this disorder. Tamoxifen citrate at
2.5 mg/kg po qd, results in a 25-50% reduction in prostate volume within 30 days. Tamoxifen also decreases
libido, serum testosterone concentrations, semen quality and testicular size and tone. While on treatment,
sperm production will cease and all semen parameters with decline gradually and libido will also decline.
Following cessation of therapy, all parameters are expected to return to normal within limits within several
months, assuming initial treatment didn’t last more than 30 days.
Anastrazole (Arimidex®, AstraZeneca) is a potent, highly selective aromatase inhibitor. A dose of 0.025 mg/kg
po qd for 28 days results in rapid reduction of prostate volume by over 20% with no effects on libido, testicular
size or tone, or semen parameters.
Gonadotropin releasing hormone (GnRH) agonist therapy. Deslorelin acetate® (Suprelorin, Virbac) and azaglynafarelin (Gonazon®, Intervet) are potent GnRH agonists that decrease LH production by desensitizing pituitary
gonadotrophs to GnRH and Leydig cells to LH. Following a brief stimulatory period after implant placement,
there is long term downregulation of testicular function resulting in poor to no libido and a cessation of
spermatogenesis, along with a decrease in prostate volume by as much as 55%. Semen parameters and libido
return to normal within 3 months of implant withdrawal. These implants are not labeled for use in the US.
Prostatitis
Prostatitis is a common disease entity in intact male dogs. Dogs with BPH are predisposed. Clinical signs
depend on whether the condition is acute or chronic; with acute cases presenting as sick patients with obvious
inflammatory disease and chronic prostatitis cases typically being subclinical in nature. Infection occurs due to
ascension of bacteria from the urethra, scrotal contents, bladder or hematogenously. Aerobic bacteria such as
Escherichia coli, Staph spp, Strep spp, Pseudomonas, Pasteurella, Proteus, Mycoplasma and Ureaplasma are all
common pathogens, along with any other opportunistic bacteria that may be present. Anaerobic infection is
less common but possible. Fungal organisms (particularly Blastomyces) have an affinity for the prostate and
testicles and should be considered if signs of systemic fungal infection are present.
Dogs with acute prostatitis may present with fever, malaise, dehydration, vomiting, diarrhea, stiff/stilted hind
limb gait, back pain, +/- abdominal pain. There may be hemospermia, hematuria, pyospermia, or pyuria.
Semen quality and libido may be decreased. It can be difficult to determine if bladder or prostate infection
was the initiating cause as the two tracts are so interconnected. Rectal examination will typically reveal an
enlarged, asymmetrical and painful prostate, if it can be palpated in the pelvic canal. If the prostate is markedly
enlarged it may reside entirely in the abdominal cavity. Diagnostics include ultrasonography (heterogenous
architecture with hypoechoic parenchyma with or without cavitation), radiography, prostatic fluid evaluation
(collection is often impossible due to pain associated with ejaculation, so prostatic massage, under sedation,
may be necessary), complete blood count (CBC) and serum chemistry. Cytology usually reveals increased
numbers of neutrophils often with intracellular bacteria. Culture of prostatic fluid is recommended for
aerobic, anaerobic and/or fungal (if suspected) organisms. Fine needle aspiration or core biopsy is
contraindicated in cases of suspected acute prostatitis because the needle tract may be seeded with bacteria.
Dogs with chronic prostatitis are typically asymptomatic unless they have concurrent signs of BPH. They may
present with infertility due to descending testicular/epididymal infection or alterations in prostatic secretions
(ph and osmolarity). Rectal palpation may reveal an asymmetrical, non-painful, but enlarged, prostate.
Diagnosis is via ultrasonography (enlarged, asymmetrical, heterogenous architecture with normal to slightly
hyperechoic echotexture), cytology and culture of the third fraction (collected either by ejaculation, prostatic
massage or FNA), culture of the third fraction or by prostatic aspirate or core biopsy, and histopathology via
core biopsy. Cytology may or may not reveal increased numbers of neutrophils depending on whether the
infected areas of the prostate are walled off to the secretory ducts; therefore a lack of neutrophils, does not
rule out chronic prostatitis. In long-standing cases of chronic prostatitis, the gland may actually be smaller
than normal, due to fibrosis and contracture, but it is still asymmetrical and non-painful.
Prostatic abscessation may occur with acute prostatitis. It is difficult to differentiate retention cysts from
abscessation on ultrasound, so this is typically determined based on risk and clinical picture (dogs with acute or
chronic prostatitis are at high risk for abscessation, while dogs with BPH are not). Complete blood count
usually reveals a marked leukocytosis with neutrophilia and a degenerative left shift with prostatic
abscessation.
For dogs no longer being used for breeding, castration with appropriate antibiotic therapy and supportive care
is indicated as soon as the patient is stable. For breeding males, treatment involves supportive care (IV fluids,
NSAIDs, pain management), appropriate antibiotic therapy based on culture results and treatment of
concurrent BPH.
With acute prostatitis, the blood-prostate barrier is broken, allowing most antibiotics access to the prostatic
tissue. In a normal prostate, antibiotic penetration occurs via concentration gradients and diffusion. The bloodprostate barrier normally only allows lipophilic drugs that are not highly protein bound to diffuse across. The
pH of the prostate is more acidic than blood (normal pH of prostatic fluid is 6.1-6.5). Ion trapping also affects
the ability of antibiotics to penetrate the intact prostate. All drugs have a charged fraction (ionized) and an
uncharged fraction. The uncharged fraction of lipophilic drugs equilibrate on both sides of a membrane, while
the charged portion concentrates on one side or the other depending on pH of the fluid on either side of the
membrane. Drugs are more concentrated on the side with greatest ionization. Thus in a normal prostate,
weak bases will concentrate within the prostatic tissue (since the secretions are acidic). If prostatic secretions
are altered, and pH is more basic, weak acids may be a better choice. With chronic prostatitis, antibiotics
should be continued for at least 4-6 weeks and sometimes longer. The prostatic fluid should be recultured and
ultrasound repeated at the end of treatment to ensure complete resolution. These dogs will be predisposed to
recurrent infection.
Good antibiotic choices include the fluoroquinolones, trimethoprim-sulfa, the macrolides and
chloramphenicol. The fluoroquinolones are zwitterions (have both a positive and a negative charge), they are
not basic or acidic, and therefore penetrate the prostate regardless of pH. They are effective against most
aerobic bacteria including Mycoplasma and Ureaplasma. They are not effective against fungal organisms or
anaerobes. They are typically the antibiotic of choice while waiting for culture results. Trimethoprim is a weak
base and has broad spectrum activity, but may be associated with side effects with long term use (i.e.
keratoconjunctivitis sicca, blood dyscrasias). The macrolide antibiotics (erythromycin, tylosin) penetrate the
prostate well but are only effective against gram positive organisms so should not be used until a sensitivity
has been obtained. Chloramphenicol crosses the blood-prostate barrier well and is effective against
anaerobes. Humans should wear gloves when administering this medication to their pets.
Prostatic abscesses usually require surgical drainage unless they are very small, as it is difficult to get high
enough antibiotic concentrations into the center of the abscess. Large prostatic abscesses or those close to
the surface of the gland are at high risk for rupture into the abdominal cavity resulting in septic peritonitis and
a very high mortality rate. Surgical techniques include omentalization, marsupialization and penrose drain
placement. Omentalization is currently the surgical treatment of choice. There are more complications with
penrose drain placement and marsupialization so these are typically only used if omentalization is not
successful.
Prostatic Cysts
These may occur within the parenchyma (retention cysts) and are associated with BPH or they may be
paraprostatic (remnants of the tubular paramesonephric ducts). Cysts may cause no signs at all, or if they
become large enough may cause stranguria, dysuria, tenesmus or constipation. Intraprostatic cysts predispose
to abscessation. Paraprostatic cysts can be surgically resected. Treatment for BPH will often reduce the size of
smaller retention cysts, but large retention cysts require surgical removal, using the same techniques
described above for abscessation.
Prostatic Neoplasia
Adenocarcinoma and transitional cell carcinoma are the 2 most common neoplastic conditions of the canine
prostate. These neoplasms tend to be aggressive and metastasize quickly. Liver and lung are the most
common metastatic targets. Prostatic neoplasia is not androgen dependent and as such occurs more
commonly in neutered males than intact males. Androgens may in fact be protective against neoplastic
transformation. Castration may also cause a shift in the prostatic stroma from actin-positive smooth muscle
cells to vimentin-positive mesenchymal cells, which may favor tumor formation. Furthermore, castrated
animals may live longer than their intact counterparts predisposing them to age-related neoplastic processes.
Clinical signs may include dysuria, stranguria, tenesmus, constipation, back pain, stiff/stilted hind limb gait, or
abdominal pain. Rectal palpation may reveal a painful prostate if it can be palpated. Diagnosis is via
ultrasonography (heterogenous architecture, asymmetrical), FNA, or core biopsy. Diagnosis does not tend to
occur until late in the disease process and metastasis are common.
Treatment is usually palliative and does not result in significantly extending the lifespan of the patient. Surgery
may be considered if there are no signs of metastasis and involves total prostatectomy. Urinary incontinence is
common following this procedure. Another surgical procedure is subtotal intra-capsular prostatectomy (open
procedure or with Nd:YAG laser). There may be increased survival time with this procedure and less chance of
urinary incontinence. Transurethral resection of the prostate is a third surgical possibility and results in
decreased clinical signs but no improvement in survival time. Dogs with dysuria may benefit from tube
cystotomy or urethral stent placement.
Radiation therapy does not improve quality of life or extend survival times and is fraught with complications
including colitis, GI stricture or perforation, skin ulceration, bladder wall thickening, chronic cystitis, urethral
stricture, ileosacral osteosarcoma, osteopenia, pelvic limb edema, and perianal pain. At this time, radiation
therapy is not a viable treatment alternative.
Non-traditional chemotherapy with NSAIDS like piroxicam and carprofen may be of benefit because neoplastic
prostate cells express COX-2. Increased survival times (up to 7 months) may be seen with these NSAIDs. The
bisphosphates are osteoclast inhibitors and may help increase bone density and thereby decrease pain and
chances of fracture associated with metastasis. They may also control hypocalcaemia of malignancy.
Conclusion
Most dogs with prostate disease are intact. Accurate diagnosis of prostatic disorders present will allow for
appropriate therapy to treat all aspects of disease present. It is important to remember that more than one
prostatic disease may exist at one time and so all components must be addressed with appropriate therapy to
affect a successful outcome for the dog. Neutered males dogs with prostate disease will most likely be
neoplastic unless the dog was recently neutered.
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