Wade Bushman, MD, PhD

Recurrent urinary tract infections (UTIs) in postmenopausal women can be a particularly challenging problem. We acknowledge there is no clear-cut solution to this vexing problem, but various strategies can be employed that have found success.

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Asymptomatic bacteriuria is common in postmenopausal women, and the incidence increases with age, diabetes, and sexual activity. There is a correlation of bacteriuria with risk for symptomatic UTI; however, it is not recommended to treat asymptomatic bacteriuria, as it may paradoxically increase the risk of symptomatic UTI. The goal, then, is to treat as necessary but to avoid overtreatment.

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UTIs in postmenopausal women may occur with typical symptoms (urgency, frequency, dysuria, incontinence, and foul odor) or fever. In some patients, such as those with impaired mentation, the diagnosis can be less obvious and is often implicated as a causative factor in temporary decreased cognition. In patients with a history of lower urinary tract symptoms (LUTS), symptoms may be exacerbated by UTI, but in the absence of typical UTI symptoms it is often difficult to determine whether an up-tick in LUTS is really due to UTI or is simply symptomatic fluctuation superimposed on asymptomatic bacteriuria.

The appropriate management of a patient presenting with “recurrent UTIs” starts with an appropriate evaluation.

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First, a detailed history must be taken to elicit symptoms, severity (fevers, hospitalizations, ER visits), frequency (weekly, monthly), microbiology (organisms and resistance patterns), comorbidities, prior evaluations, treatments, and responses to date. Contributing conditions may be identified on physical examination, bimanual and vaginal exam, and post-void residual measurement.

A key step is to elicit the symptoms associated with reported UTI episodes and match them with laboratory findings. Many times, the patient’s urinary symptoms are not due to bacterial infection. This distinction is critical to make, since prevalence of both asymptomatic bacteriuria and LUTS is high in elderly women and bacteriuria may be inappropriately implicated as the cause of the patient’s troubles. In fact, patients may have primary voiding dysfunction and the diagnosis of “recurrent UTIs” may result from the follow-up cultures obtained by a diligent primary care physician after antibiotic treatment that really only shows re-colonization with asymptomatic bacteriuria.

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If a history is obtained that is consistent with recurrent bacterial UTIs with associated symptoms and prompt response to culture-directed antimicrobial therapy, then the next step is to rule out recurrent UTIs due to a hidden nidus of infection such as a stone, tumor, or foreign body. The tip-off is quickly relapsing infection with the same organism. If this is found, then a complete urologic evaluation with upper tract imaging and cystoscopy is indicated. In patients with recurrent UTIs with a variety of organisms and no history of febrile infection, neither cystoscopy nor upper tract imaging is necessary and the focus moves to management: treatment of contributing factors, prevention, and antibiotic treatment.

Vaginal atrophy is common in postmenopausal women and can be identified on pelvic examination by the appearance of dry, friable, and thin mucous membranes. The pathogenesis of recurrent UTIs is believed to be due to alterations in bacterial flora, changes in vaginal pH, and breakdown of natural mucosal barriers preventing ascending infection. The mechanism of local estrogen replacement stimulates blood flow, increases pH, and aims to restore mucosal barriers. A Cochrane review from 2008 cited two randomized clinical trials (RCTs) showing that vaginal estrogens reduced the recurrence of UTIs compared to placebo with RR of 0.25 and 0.64 in each study 

 No such benefit was found with oral estrogens.

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In our practice, if there is evidence of vaginal atrophy on pelvic examination, we strongly consider such an approach. The risks for local therapy are very low, with the most common side effect being local irritation.

The use of probiotics is controversial. Some RCTs show benefit while others do not. A major confounder is that the term “probiotics” is not specific. It includes oral and vaginal administration and may utilize either specific or multi-strain regimens. Thus, meta-analysis interpretation is limited. Furthermore, few studies looked specifically at UTIs in postmenopausal women. The purported mechanism of action of probiotics is to establish vaginal colonization that acts as a barrier to ascending infection, prevent re-colonization of the vagina by potential uropathogens, and modulate host defenses.

The most compelling evidence is for use of intravaginal suppositories of 

 In a recent RCT, use of such an approach had a relative risk of 0.50 in young women 

 Given the low risk-benefit profile of intravaginal suppositories taken on a weekly basis after treatment of the acute UTI, this tends to be an attractive option for patients interested in non-antibiotic-based approaches. If intravaginal Lactobacillus suppositories are not available at a retail pharmacy, patients may be directed to online retailers such as Amazon.

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Cranberry extracts or cocktails taken on a daily basis are believed to reduce the risk of recurrent UTIs. The magnitude of their effect is somewhat under question as highlighted by a recent Cochrane analysis, but several RCTs and meta-analyses have demonstrated benefit compared to placebo 

 Some of this variation may be due to lack of standardization of treatment. Nevertheless, cranberry extracts are an inexpensive, well-tolerated dietary supplement that has evidence supporting its use.

Antibiotic prophylaxis is a highly effective way to reduce the incidence of recurrent UTI. The agents most commonly used are trimethoprim-sulfamethoxazole or trimethoprim (Bactrim, Sulfatrim), ciprofloxacin (Cipro, Proquin), cephalexin (Keflex), and nitrofurantoin (Macrobid, Furadantin, Macrodantin) (table). Standard dosing regimens use low-dose nightly administration to produce effective antibiotic concentrations in the urine without inducing resistance in the gut flora. This is critical since the gut is the source of potential uropathogens and higher doses will compromise the effectiveness of the prophylactic regimen.

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The recommended doses are trimethoprim-sulfamethoxazole, 400/80 mg; ciprofloxacin, 250 mg; and cephalexin, 250 mg. Trimethoprim, 80 mg can be used in patients with sulfa allergy.

Nitrofurantoin is a very useful prophylactic agent, especially because it is effective against many extended spectrum beta lactamase-producing 

and is less likely to breed resistance, but use in the elderly is generally discouraged because of a relatively higher risk of serious side effects, including pulmonary fibrosis. Its use should therefore be based on a careful consideration of benefit versus risk. In postmenopausal women whose UTIs are clearly related to sexual activity, post-coital prophylaxis can be prescribed.

Several studies have demonstrated that women, when appropriately counseled, can reliably recognize the symptoms of UTI and initiate empiric treatment. The concept of self-start therapy is to provide the patient with a treatment for early intervention for UTIs that occur with modest frequency (3-6 times per year). They are prescribed a single agent, and at the earliest signs of infection start therapy for a full treatment course-typically 3 days for an uncomplicated UTI. If symptoms do not respond quickly or are associated with fever, then they must seek prompt medical attention.

Self-start therapy often alleviates patient anxiety, reduces the time-to-treat, and provides the patient with a sense of control. However, it must be emphasized that this strategy is recommended only for a highly reliable patient who has been thoroughly evaluated and appropriately counseled.

Recurrent UTI in the postmenopausal woman is a common problem that can be effectively addressed by a step-wise approach that produces historical and laboratory evidence for recurrent symptomatic UTIs, rules out bacterial persistence and relapsing infections that merit further diagnostic evaluation, identifies and addresses contributing conditions, and offers the patient an effective regimen of prophylaxis or self-start therapy. This entity should be distinguished from asymptomatic bacteriuria, which should be managed conservatively without antibiotics.

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Although there is no clear-cut solution to the problem of recurrent UTIs in postmenopausal women, "various strategies can be employed that have found success," write Wade Bushman, MD, PhD, and Brian V. Le, MD, MA.

Wade Bushman, MD, PhD

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How to manage recurrent UTIs in postmenopausal women