Chronic Pelvic Pain in Men Medication

By definition and exclusion, nonbacterial prostatitis, or prostatodynia, is without a documented bacterial origin. Antibiotics should have a very limited role in therapy for this condition. However, in desperation to do something for the patient, multiple courses of antibiotics are frequently prescribed, often for extraordinarily protracted periods.

Keep in mind that no antibiotic regimen has been proven to be efficacious in the treatment of chronic nonbacterial prostatitis. According to Meares, "Antibacterial agents are neither effective nor indicated in the treatment of nonbacterial prostatitis."^{[28, 29, 30]} If U urealyticum or C trachomatis infection is suggested, a trial treatment of antibiotics may be considered.

In bacterial prostatitis, antibiotic therapy may be guided by culture findings from the prostatic secretions, from the ejaculate, from a urethral swab, or from the spun sediment of a VB₃. Even in this scenario, choosing the antibiotic is confounded by the fact that the organisms cultured from these sources may reflect urethral contaminants rather than a true pathogen.

In an aggressive attempt to clarify the presence of bacteria in the uncontaminated prostate tissue of men with chronic pelvic pain syndrome (CPPS), researchers in Seattle concluded that, while the prostatic colonization of bacteria within the prostate is not uncommon, particularly in older men, prostatic bacteria are probably not etiologically involved in the symptoms of most men with CPPS. The investigators performed digitally guided transperineal prostate biopsies in 118 subjects with CPPS and in 59 control subjects. They found no significant difference in the rates of positive cultures (38% vs 36%).^[31]

Some patients with CPPS are maintained on long-term, low-dose regimens, such as 1 tablet of trimethoprim-sulfamethoxazole (Septra DS) daily. In some cases, patients experience symptomatic relief while on these regimens. Whether this is a reflection of the strong placebo effect associated with treatment of this condition or the result of suppression of an undetected pathogen is purely a matter of speculation. Studies suggest that, beyond the placebo effect, certain antibiotics may actually be providing an objective anti-inflammatory and/or analgesic benefit to these patients.

In screening for a bacterial etiology, the finding of gram-positive organisms has often been dismissed as a contaminant. However, small studies have found evidence to suggest that anaerobes and gram-positive aerobes, even coagulase-negative staphylococci, may in fact be pathogens, and appropriate antibiotic therapy has proven effective in select cases.^[32]

In approaching the antibiotic option, remember that no antibiotic is free of complications. Regarding a blinded trial of antibiotics for prostatodynia, many have commented that the antibiotics cannot hurt. As a grim reminder of the rare, but devastating, consequences attendant to the casual use of such antibiotics, the primary author consulted on the treatment of a patient who experienced life-threatening complications following liver/kidney transplantation that was necessitated by his extremely adverse reaction to a course of trimethoprim-sulfamethoxazole. Tragically, the symptoms of chronic prostatitis (CP), for which this antibiotic was prescribed, were later proven to be manifestations not of prostatitis, but of a bladder neck contracture.

It should also be kept in mind that the expense of antibiotics is not negligible, particularly when multiple prescriptions are provided for the newest, most expensive wide-spectrum antibiotics.

The Urologic Diseases in America Project, reviewing Veterans Health Administration datasets, found that men with CP/CPPS were 7 times more likely to have received a fluoroquinolone than were men without this condition. An increased use of other antibiotics was also observed. Despite the evidence that antibiotics are not effective in most men with CP/CPPS, they were prescribed in 69% of men with this diagnosis, suggesting that strategies to reduce unnecessary antibiotic use in these patients are warranted.^[33]

In an editorial published in the Journal of Urology, Professor Richard Berger speculated that, while considerable evidence suggests that antibiotics are no more effective than placebo in the treatment of CP/CPPS, this finding may be contrary to common experience, as the success rate associated with placebo has been approximately 50%. Thus, half of these men fare better whenever they are given something. It would not be surprising if the most common cause of inappropriate antibiotic prescriptions by urologists were for CP/CPPS type III, and if it were a major contributor to fluoroquinolone antibiotic resistance.^[34]

Berger observes, "Because of our inappropriate nomenclature of 'prostatitis,' (when it is neither an infection nor an inflammation) and the message given by our antibiotic treatment, many men end up thinking they have an incurable but unknown infection. Old habits are hard to change, but need to be replaced by patient education, and perhaps by physical education and pain-directed drug therapy."^[35]

In a controlled, randomized investigation by the Chronic Prostatitis Collaborative Research Network-2, pregabalin (Lyrica) failed to show an advantage in relieving discomfort, as measured by the NIH Chronic Prostatitis Symptom Index. The problem was that while 47.2% of the men experienced significant (>6-point) relief when taking pregabalin, 35.8% of the men who were taking a placebo also experienced relief. Patients taking pregabalin fared better on the McGill Pain Questionnaire. Despite these findings, clinicians still hold that pregabalin may have a role in pain relief for select CP/CPPS patients. It is important to bear in mind that use of pregabalin is not US Food and Drug Administration approved for the treatment of CP/CPPS pain.^[36]

Class Summary

Chronic pelvic pain syndrome (CPPS) in men should, by definition, exclude men with a proven bacteriologic etiology. Therefore, antibiotics should not be deemed appropriate for the treatment of this condition. However, most practitioners are inclined to attempt at least 1 trial of long-term antibiosis.

Clinical evidence upon reviewing the results of all available clinical trials indicates limited validation for the use of antibacterials, even in the face of chronic bacterial prostatitis. The cure rates for sterilization of prostatitic secretions, even for this more specific indication, ranged from 0-90% and correlated poorly with symptomatic responses. Limited evidence from retrospective studies suggests that quinolones (eg, ciprofloxacin [Cipro], levofloxacin [Levaquin]) may be more effective than trimethoprim-sulfamethoxazole (Bactrim, Septra).

Minocycline (Dynacin, Minocin)

Minocycline helps to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible chlamydial, rickettsial, and mycoplasmal organisms.

Erythromycin (E.E.S., E-Mycin, Ery-Tab)

Erythromycin is a macrolide antibiotic with the theoretical advantage of penetrating the blood-prostate barrier, but it carries an increased incidence of gastrointestinal (GI) intolerance.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone with activity against Pseudomonas species, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, and most gram-negative organisms, but no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared.

Class Summary

Tension myalgia of the pelvic floor muscles, combined with overall stress-related tension, can be partially relieved with muscle relaxants.^{[28, 29, 30]}

Diazepam (Valium, Diastat)

Diazepam is a benzodiazepine derivative indicated for short-term relief of anxiety and adjunctive relief of skeletal muscle spasm. It depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). Individualize the dosage and increase it cautiously to avoid adverse effects.

Class Summary

These agents have become a mainstay in the symptomatic treatment of chronic pelvic pain syndrome (CPPS) in men.^{[28, 29, 30]} These agents, by relieving the secondary smooth muscle spasm within the bladder neck and prostatic urethra, afford the patient greater comfort in voiding. The dosage should be titrated progressively and administered at night to minimize the main adverse effect of orthostatic hypotension. The final dose must be individualized to meet the patient's needs.

While the antihypertensive agent has been administered to patients already taking other blood pressure medications, coordinating the addition of this medication with the primary care physician or cardiologist who is prescribing the patient's other antihypertensive medications is wise.

Again, as with other medications, such as antibiotics, remember that the use of alpha-adrenergic blockade is not approved by the US Food and Drug Administration (FDA) for the treatment of prostatodynia. One study suggested an advantage to the use of alpha blockers in combination with antibiotics over antibiotic therapy alone in the treatment of chronic bacterial prostatitis.^[34]

Doxazosin (Cardura)

Quinazoline compounds counteract alpha1-induced adrenergic contractions of the bladder neck, facilitating urinary flow in the presence of benign prostatic hyperplasia (BPH).

Terazosin (Hytrin)

Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of the bladder neck, facilitating urinary flow in presence of BPH. Reporting at the annual convention of the American Urological Association, researchers confirmed a significant, albeit limited, value for alpha1-blockers in the management of CPPS. Patients with CPPS treated with terazosin showed a 56% improvement in their NIH-CPSI scores; however, placebo controls showed a 36% response rate.

In a parallel report from Finland, using the selective alpha-blocker alfuzosin, modest improvement again occurred. After 6 months, 19 patients on alfuzosin showed significant reduction in pain scores but not in voiding or quality-of-life scores. This finding seems counterintuitive in that one would expect an alpha blocker to have its most dramatic effect on voiding performance. Moreover, unlike BPH treatment, in which a response to alpha blockers is prompt, the symptomatic response in patients with CPPS can take 6 months or longer to mature.

These studies raise the question of whether the expense and nuisance of these long-term medications are warranted for this modest response, which is in close competition with the placebo effect.^[37]

Tamsulosin (Flomax)

Tamsulosin is an alpha-adrenergic blocker that specifically targets A1 receptors. It has the advantage of causing relatively less orthostatic hypotension and requires no gradual up-titration from the initial introductory dosage. On the other hand, the rate of ejaculatory dysfunction is higher with this medication (8.4-18.1%).