Page 525 - WSAVA2018
P. 525

medroxyprogesterone acetate, delmadinone acetate, chlormadinone acetate and ciproterone acetate have been successfully used in the dog, although for the majority of them there is only a limited amount of experimental data on their effectiveness in the canine. Their action causes a sort of pharmacologic castration and is rather precociously observed during treatment, as improvement can be observed already after 7-15 days. Medroxyprogesterone acetate has been used as a single SC dose of 4 mg/kg; although prostatic effects were
not assessed, the treatment significantly reduced serm testosterone concentrations, which implies that it might be used also for the treatment of BPH18. Chlormadinone acetate has been used at the dose of 1-2 mg/kg orally for 1 month, or as a subcutaneous 12-month implant of 5.0 mg/kg19, but oral doses as low as 0.03 to 0.3 mg/ kg/day are effective in dogs with BPH20. Delmadinone acetate has also been used at doses of 1.5 to 5.0 mg/ kg SC to be repeated every 1-2 weeks21-23 with the
lower dosage being the one prescribed in commercial veterinary formulations. Ciproterone acetate is another progesterone derivative with a very strong antagonistic effect on DHT receptors when used at the daily dose
of 0.5-1.0 mg/kg per os for at least 2-4 weeks; the drug is well tolerated in dogs and causes decreased libido and spermatogenesis and reduces prostatic size24-25. We currently use it as an adjunct treatment in dogs with acute clinical signs of BPH such as rectal compression, urethral compression or signs of prostatitis. Cyproterone acetate has a very quick action with signs disappearing already at the end of the first week of treatment, therefore it is helpful whenever the dog is suffering
from signs related to BPH or when a worsening of the condition is anticipated such as during the first 1-2 weeks following administration of a GnRH agonist implant (see over). Its effects are rather long-lasting, with a 3-4 week course of oral administration being enough to maintain the dog for a few months without clinical signs.
Osaterone acetate (OA) is a more recent progesterone derivative commercially available in several European countries as a veterinary product for use in dogs
with BPH26,27. As an antiandrogen, OA is an analog of chlormadinone acetate (but it is 5 times more potent in vitro than chlormadinone itself) with a specific inhibitory action on prostatic volume in laboratory animals and dogs23. It is marketed as an oral medication with
each package containing 7 pills of different dosages depending on body weight: 1.875 mg, 3.75 mg, 7.5 mg and 15 mg for dogs of 3-75 kg, 7.5-15 kg, 15-30 kg and 30-60 kg, respectively. Dosage is 0.25-0.50 mg/kg. Treatment consists of 1 pill/day for 7 consecutive days. OA is slowly metabolized by the liver with a very long half-life of 198+110 hr. For this reason, a 7-day course of treatment allows for a pharmacological concentration of the drug to last for 6 months. OA is very effective
in treating canine BPH, and works well also in case of
prostatitis28. Being a progestogen derivative, OA may cause suppression of the pituitary-hypophysial-adrenal axis with reduced cortisol production and/or low or no response to ACTH stimulation tests lasting for days
or weeks after treatment withdrawal. Although this is normally not a problem in healthy dogs, it should be considered when dealing with post-operative cases or in case of trauma, while treatment with OA should be avoided in dogs with hypoadrenocorticism. Semen quality appears not to be affected initially, and may actually improve when poor at treatment onset due to the prostatic condition. However, progestogens are known to cause a progressive deterioration of semen quality with time; in the case of OA, there is little if
any data on fertility during the last half of the 6-month treatment.
Non-steroidal antiandrogens – Non-steroidal antiandrogens include finasteride and flutamide. Finasteride inhibits 5-a-reductase (the enzyme responsible for the final transformation of testosterone into di-hydro-testosterone or DHT) thereby lowering
the concentration of DHT which is the active metabolite at the level of target tissues, without altering serum testosterone concentrations. This leaves spermatozoa production undisturbed, which makes finasteride a
good choice for breeders (although a chronic use may be associated with a decrease in ejaculate volume as well as decrease in semen quality). Finasteride is only approved for use in men, but it is well known to produce a dose-dependent decrease in prostatic size also in dogs. It can be used at the daily dose of 1 mg/kg/day, PO, for up to 4 months resulting in a 50%–70% reduction in prostatic hypertrophy with no negative effect on semen quality29. Lower dosages of finasteride (0.1-0.5 mg/kg/ day, PO, for 4 months) cause a slightly lower but still curative effect in terms of reduction of prostatic volume by >40%, resolution of clinical signs, reduction of DHT concentration, maintainenance of normal testosterone levels, and have no deleterious effect on semen quality, fertility, or libido30. The low dosage (0.1–0.5 mg/kg) of finasteride allows for a convenient dosing of one 5-mg capsule/day for dogs weighing 10–50 kg; however, it is advisable to use 1.5 mg (approximately 1/3 of a 5.0 mg pill) for dogs <15 kg body weight, 2.5 mg (approximately half pill) for dogs of 15-30 kg body weight, and 5.0 mg
for dogs of >30 kg body weight. Finasteride is well tolerated and can be administered for long periods of time. We currently use finasteride in breeding dogs both to induce remission of clinical signs of BPH as well as
to keep the condition under control with 1-2 treatment cycles/year depending on severity of clinical signs. Unlike cyproterone acetate, finasteride is fairly slow to show its efficacy, as clinical signs may take up to 3-4 weeks to disappear, and tend to appear again within a few weeks of treatment withdrawal. Flutamide is a human antiandrogen which can cause a significant decrease
Your Singapore, the Tropical Garden City

   523   524   525   526   527