Introduction

Urinary incontinence is common in dogs and is a frequent reason that owners bring their dogs to a veterinarian. Urethral sphincter mechanism incompetence (USMI) is the most common cause of urinary incontinence in adult female dogs and is estimated to affect between 5 and 20% of spayed female dogs.^1–5 Though the true prevalence of USMI in the total male canine population remains unknown, one report of urinary incontinence in dogs found that adult male dogs accounted for only 9 of 320 cases.³ The etiology and pathogenesis of this condition in male dogs have not been determined; however, comparison with continent dogs has identified many risk factors, including a shorter urethral length, caudal bladder position, and castration.^6–8 Urethral sphincter mechanism incompetence in male dogs is defined as involuntary leakage of urine due to decreased urethral tone after the exclusion of other causes, such as prostatic disease, bladder or urethral calculi, bladder or urethral neoplasia, lower urinary tract infections, ectopic ureters, and neurologic dysfunction. The gold standard for the diagnosis of USMI in both male and female dogs is urethral pressure profilometry. However, since this technique has limited availability, history, clinical signs, physical exam, imaging of the urinary system, urinalysis, and urine culture typically make the diagnosis in both sexes.

The options for management of USMI in male dogs are limited. Medical management with phenylpropanolamine (PPA), estrogens, or anticholinergic drugs has been reported; however, the overall reported response to these agents is poor. Although a prospective study evaluating urinary incontinence in dogs found that seven of eight male dogs included in the study had resolution of incontinence as well as significant increases of their urethral pressure profile values following oral PPA administration, a larger retrospective analysis of 43 male dogs treated with various drugs for USMI found that only 7 dogs (16%) had an excellent response to medical therapy, and 28 (65%) had a poor response.^6,9 Small case series have been published describing surgical techniques used in the management of USMI in male dogs. While prostatopexy was only successful in one of nine dogs reported in one case series, urinary continence was restored in three of seven dogs that underwent the relocation of an intrapelvic bladder neck to an intra-abdominal position.^10,11 Likewise, two of four males that received a single intraurethral polytetrafluoroethylene injection became continent.⁴ More recently, the use of artificial urethral sphincter devices has been reported in dogs.¹² Although only three male dogs were included in this study, their continence scores increased significantly when compared to presurgical scores.

Testosterone administration is an alternative medical therapy that has been used in male dogs with urinary incontinence. The management of a small number of castrated dogs with methyltestosterone was attempted in one retrospective study.⁶ The drug was reported to be ineffective, with a “poor” response in four of five dogs and a “good” response in one dog. Though testosterone cypionate^a, a testosterone ester, is recommended as a medical therapy for male USMI in many veterinary textbooks, its successful use in an incontinent male dog is only reported in a single case report.^13–15 Testosterone has potential adverse effects, including prostatic hyperplasia and behavioral aggression caused by excessive androgenic action. The frequency of the development of adverse effects in male dogs receiving this medication for management of urinary incontinence has not been reported. Therefore, the objective of this case series was to report the clinical efficacy and adverse effects of testosterone cypionate administered to a small group of castrated male dogs with incontinence presumed to be caused by acquired USMI.

Materials and Methods

Results

Eleven neutered males were identified for inclusion in the study. During the same period studied, a total of 123 spayed female dogs were seen at our institution for USMI. Of the 11 male dogs, two owners could not be contacted for the completion of the follow-up questionnaire, and one dog was found to be receiving concurrent treatment with both PPA and testosterone cypionate. Eight dogs were included in the series (Table 1). Median follow up, as defined as the period between the beginning of testosterone therapy and the phone interview, was 25.5 mo (range: 2–67 mo). The median age of the dogs was 7.5 yr. The median age of castration for the eight dogs for which it was known was 1.5 yr (range: 6 mo to 3 yr). Urinary incontinence in all dogs was first noted at a median age of 3.5 yr (range: 6 mo to 8 yr) and occurred during rest and recumbency in seven of eight dogs. The remaining dog dribbled urine continuously, especially during or following activity. Five of eight dogs had received previous medical treatment for urinary incontinence including diethylstilbestrol (DES) and PPA. Of these five dogs, all had either failed to respond to medical management or had initially responded but then incontinence recurred.

TABLE 1 Patient Data, Imaging, and Previous Treatments for Incontinence

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Physical exam failed to identify an underlying cause for the urinary incontinence of the dogs included in the study. Rectal examinations were recorded for six of eight dogs in the study and were unremarkable. Neurologic examinations, performed in all dogs, were unremarkable. Urinalyses and aerobic cultures were available for all cases. Median urine specific gravity was 1.025 (range: 1.010–1.044). In no cases were pyuria, hematuria, cylinduria, or bacteriuria reported. One case (dog 1) had glucosuria detected and was identified as being diabetic, based on concurrent hyperglycemia and increased fructosamine value. Significant bacterial growth (Proteus mirabilis) was isolated from the urine of one dog (dog 3); urine from all other dogs did not yield bacterial growth after 48 hr of aerobic culture. Urinary tract infection was not judged to be the cause of incontinence in dog 3 based on the fact that incontinence persisted after treatment with amoxicillin-clavulanic acid selected on the basis of microbial culture and sensitivity. The urinary tract of each dog was assessed by ultrasound, positive contrast cystourethrogram, and cystoscopy in seven, three, and two cases, respectively (Table 1). Relevant imaging findings such as a dilated urethra, evidence of cystitis, and prostatomegaly were identified in two, one, and one cases, respectively.

The median dose of testosterone cypionate was 1.8 mg/kg (range: 1.0–2.2 mg/kg) administered intramuscularly for a median dosing interval of 4.5 wk (range: 3–6 wk) (Table 2). The median number of treatments was four (range: 2–25). Owners scored a median satisfaction score of 1.5 (range: 1–4), with three of eight owners reporting that their dog had either a good or excellent response to testosterone cypionate. One of eight owners indicated a fair response, and four of eight owners indicated a poor response. No adverse effects were reported in any dog. In two dogs, satisfaction was deemed sufficient to warrant the continued use of testosterone.

TABLE 2 Testosterone Cypionate Dosing Schedule and Response

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Discussion

In the present study, treatment with testosterone cypionate was retrospectively evaluated in eight dogs. In five of these dogs, previous treatments with either PPA or DES had been unsuccessful. Despite this, testosterone cypionate resulted in good or excellent control in only three of eight dogs based on assessment by the dogs’ owners. The most common medical therapies for USMI in female dogs are PPA and estrogens. The success rate of PPA alone in female dogs has been reported to be as high as 85–90%, while the response rates for estrogens has been reported to range from 18–65%.^2,16,17 The response rate to PPA and DES in male dogs has been reported to be substantially lower in some studies, with complete response reported in only 31 and 37% of male dogs, respectively.⁶

Factors proposed to be important in maintaining continence in healthy male dogs include a long proximal urethra, increased urethral tone generated by the prostate, and, potentially, differences in follicular stimulating hormone and luteinizing hormone receptors located in the urethra and bladder.¹⁸ The mechanism through which testosterone cypionate improves urinary continence in males is poorly understood. Though purely speculative, hypertrophy of the prostate, mediated by nuclear androgen receptors, has been proposed to play a role in maintaining urinary continence.^19,20 In addition, functional effects mediated through phosphodiesterase-5 as well as α₁-adrenergic receptors are thought to be important in maintaining tone of the bladder and urethral smooth muscles. All of the subjects in this study were castrated; therefore, smaller prostatic mass might have contributed to the reduced continence in these patients. Prostatic hypertrophy following treatment with testosterone cypionate, therefore, might explain the improved continence in some of these dogs; however, prostatic size following treatment was not recorded in the medical records.

The more traditional medical therapies used for USMI in both males and females, PPA and DES, are oral medications that require frequent administration to maintain continence. Diethylstilbestrol is initially given daily and then administered once weekly to maintain continence. Use of DES in males is uncommon because of the low response rate as well as the serious potential side effects, including feminization, induction of squamous prostatic metaplasia, and bone marrow suppression. Phenylpropanolamine requires long-term oral administration every 8–12 hr, and, even though clinical side effects are rarely encountered, significant increases in systolic blood pressures have only been reported in studies of continent research beagles.^{16, 21–23} Therefore, intramuscular administration of testosterone cypionate every 4 wk might offer a more convenient and safe dosing interval for some owners. Unfortunately, due to the small scale of our study, no conclusions could be made about the optimal dosing or number of treatments necessary to have the highest likelihood of a response.

Though no published data exists documenting adverse effects associated with testosterone supplementation in dogs, various pathologies including perianal adenomas, perineal hernias, and prostatic hyperplasia have been associated with increased serum testosterone levels in dogs.^24–26 In our study, no adverse effects were reported. The median number of treatments administered was four. It is possible that an increased rate of side effects would have been seen if the treatments had been continued for a longer period of time. Interestingly, the owner of the dog that received the most treatments (n = 25) did not report any adverse effects. None of the dogs in the current study were reported to have gastrointestinal signs or clinical signs suggestive of prostatic hypertrophy, such as stranguria, hematuria, and/or tenesmus. Nonetheless, owners of dogs undergoing this therapy should be cautioned to look for such clinical signs. All the dogs in this study had subsequent testosterone administration performed by their referring veterinarians. Consequently, only three of the eight dogs were reassessed at our institution while on testosterone therapy. Of the two dogs that had rectal exams recorded, no abnormalities were noted. In addition, no follow-up imaging was performed to evaluate prostatic size following testosterone cypionate administration.

A recent human clinical trial evaluating three different testosterone formulations for the treatment of late-onset hypogonadism reported the incidence of prostatic side effects after 3 mo of therapy.²⁷ These investigators documented no clinical signs suggestive of prostatic hypertrophy and no statistical difference in pre- and posttreatment prostate-specific antigen concentrations, which is a sensitive marker of increased prostatic mass in humans. Although these data suggest that the possible side effect of prostatic hypertrophy has little clinical relevance, caution is warranted in extrapolating this conclusion to canine patients until future studies involving follow-up prostatic ultrasonography have been performed. Posttreatment complete blood counts and biochemical profiles were not available for review in this group of dogs; therefore, the presence of laboratory abnormalities is unknown. Humans treated with testosterone cypionate for late-onset hypogonadism have shown no significant hematologic abnormalities after 14 wk of therapy.²⁷

This case series has several limitations. The information regarding each patient was variable, based on completeness of the medical record and the reliability of the owner to recall response to treatment and overall satisfaction when contacted for follow-up. The reliance on owners’ observations rather than urodynamic data to determine the drug’s effect is a significant drawback. Several investigators have noted a placebo effect in owners’ perception of their dogs’ continence following medical intervention.^21,28 Second, this study lacked a control group. Limited comparisons were made using previous reports that evaluated other medical therapies for incontinence (PPA and DES), but no direct comparisons between the treatments could be made. It is possible that we are reporting a group of dogs that was more difficult to treat since a substantial proportion had failed to respond to standard medical therapy prior to referral. Third, since the drug dose, dosing interval, and duration of treatment were determined based on clinician discretion as well as the patient’s response to the drug, there was no standardized treatment schedule for the patients in this study. For example, one dog received only 2 doses of testosterone cypionate, while another received 25 doses. This might have impacted the reported efficacy as well as the frequency and severity of side effects of the drug. Finally, the definitive diagnosis of USMI was not made by urethral pressure profilometry in any dog. Therefore, some of the dogs included in this study might have been suffering from incontinence due to another mechanism despite our best efforts to exclude those patients.

Conclusion

Though the results reported here are based on a small retrospective case series, our data suggest that testosterone cypionate might be an option in treating USMI in male dogs that are refractory or have contraindications to more commonly used medications. Additionally, no severe adverse effects were noted in this case series when testosterone cypionate was dosed at 1.0–2.2 mg/kg intramuscularly every 3 to 6 wk for up to 25 doses. Based on these data, prospective, multi-institutional controlled studies of the effects of testosterone cypionate in male dogs with USMI are warranted. These studies should incorporate more rigorous assessments of the patient’s anatomy using ultrasonography or computed tomography, urethrocystoscopy, urethral profilometry pre- and posttestosterone cypionate administration to more objectively monitor response to therapy, as well as regular monitoring of biochemical and hematologic parameters pre- and posttherapy.