Curr Bladder Dysfunct Rep (2014) 9:181–187
DOI 10.1007/s11884-014-0246-7
INFLAMMATORY/INFECTIOUS BLADDER CONDITIONS (S MOURAD, SECTION EDITOR)
Urethritis in Women—Considerations Beyond Urinary
Tract Infection
W. D. Ulmer & J. L. Gilbert & E. J. B. De
Published online: 15 July 2014
# Springer Science+Business Media New York 2014
Abstract Urethritis is a common condition affecting women
in the USA. The symptoms, however, are not specific to a
unique cause and are shared among a wide variety of urogen-
ital diseases. This article evaluates the current literature and
provides tools to the practicing clinician. Infections, particu-
larly urinary tract infection and vaginitis, are common causes.
The sexually transmitted infection Chlamydia trachomatis
continues to be one of the most common etiologies for ure-
thritis. Newer research provides evidence for the importance
of Ureaplasma and Mycoplasma genitalium. Mechanical trau-
ma, vaginal atrophy, chemical and mechanical exposure, and
Skene’s gland and other anatomical pathology will also be
reviewed. The diagnosis and treatment of urethritis often
require the practitioner to treat associated diseases such as
chronic pelvic pain syndrome and dyspareunia. Urethritis is
intensely symptomatic leading to a pressured office interac-
tion, and it is our intent to provide the tools for a comprehen-
sive approach to female urethritis.
Keywords Urethritis . Female . Dysuria . Vaginal . Atrophy .
Vaginitis . Vulvodynia . Non-chlamydial . Non-gonococcal .
Mycoplasma
Introduction
Urethritis is a common condition affecting women of all ages
in the USA and globally. By definition, it is simply inflam-
mation of the urethra—therefore, there is tremendous overlap
in etiology. For the purposes of this paper, we will omit
W. D. Ulmer : E. J. B. De (*)
Albany Medical Center, Albany, NY 12208, USA
e-mail: elisede@gmail.com
J. L. Gilbert
BioReference Laboratories, Elmwood Park, NJ, USA
urethritis secondary to common urinary tract infection (UTI).
There is a ubiquity of information known and available on
urethritis due to urinary pathogens: the American Academy of
Family Physicians [1••] and the European Association of
Urology [2] have published excellent resources available both
online and in print.
We will focus on urethritis in women whose symptoms do
not resolve with empiric antibiotics and/or whose urine culture
is negative. In this context, causes of urethritis may be divided
into several categories: sexually or non-sexually transmitted
infections, vulvar and hormonal conditions, anatomic abnor-
malities, chemical or mechanical trauma, and cancer. Sexually
transmitted infections are common in the general population
and account for a large percentage of non-UTI urethritis.
Much is known about gonococcal and chlamydial infections;
however, organisms such as Mycoplasma genitalium and
Ureaplasma will likely gain importance as their pathogenicity
are characterized. Vulvodynia is less common but may cause
enormous morbidity [3••]. Regardless of the cause, urethritis
is an important source of suffering for women.
The goal of this manuscript is to provide clinicians
throughout the chain of referral with the tools needed to treat
women presenting with urethral inflammation. Urologists of-
ten see these patients secondarily after initial work-up by the
primary medical doctor or emergency physician and the pa-
tient is often anxious at first meeting with documents from a
series of prior visits requiring review. We aim to map out how
these complex patients can be treated to satisfaction after
relatively straightforward investigations.
Sexually Transmitted Infections
Chlamydia and Gonococcus
Sexually transmitted infections (STIs) represent an important
etiology of urogenital pain and urethritis in women. Chlamydia
182
is the most common, with over 1.4 million cases reported in
2012 [4]. Furthermore, the actual incidence is at least twice this
stated amount at 2.8 million, as many cases proceed undiag-
nosed due to undertesting [4]. Although many may not have
complaints, common signs and symptoms include painful uri-
nation, frequency, vaginal burning and itching, mucopurulent
cervicitis, abnormal vaginal discharge, and dyspareunia. A
thorough investigation of women presenting with dysuria
should include testing for STIs as the impact on women’s health
and the economic burden of the morbidities are significant. The
possible sequelae of untreated Chlamydia and Gonococcus
include pelvic inflammatory disease, chronic pelvic pain, ec-
topic pregnancy, and infertility. In fact, the US Preventive
Services Task Force recommends annual screening for chla-
mydial infection in all sexually active, non-pregnant young
women ages 24 and younger and in older non-pregnant women
who are at increased risk [5]. Voided urine specimens or cervi-
cal swab should be obtained and sent for laboratory evaluation.
Specimens obtained for Chlamydia testing should routinely be
tested for gonococcal infections as well, which are less com-
mon but are likely to be asymptomatic. The well-established
treatment regimen of cephalosporin with macrolide or doxycy-
cline should be prescribed for suspected cases of either disease
(specifically, ceftriaxone 250 mg in a single intramuscular dose
plus azithromycin 1 g orally in a single dose or doxycycline
100 mg orally twice daily for 7 days). In cases where the
test results are available, if Chlamydia test is positive and
the gonococcus test is negative, the patient can be treated
for Chlamydia alone (azithromycin). In cases where the
gonococcus test is positive and the Chlamydia test is
negative, the patient should still be treated with dual
therapy to counter gonococcal resistance to ceftriaxone
(www.cdc.gov).
Non-chlamydial and Non-gonococcal Urethritis
Herpes
Viral infection by the herpes simplex virus may be a cause of
urethritis in women. Urethritis in association with herpes
simplex virus may be accompanied by painful, visible blisters;
however, many women will have only intraurethral herpes
simplex virus infection or small meatal ulcers without external
lesions. The gold standard for testing had been viral culture
from the lesion, but the more recently available polymerase
chain reaction (PCR) testing of the lesion is more sensitive
than culture for herpes simplex virus (HSV). Testing can also
be performed using direct fluorescent antibody testing of a
lesion. Antiviral regimens of acyclovir, famciclovir, or
valacyclovir taken regularly are known to reduce frequency
of episodes.
Curr Bladder Dysfunct Rep (2014) 9:181–187
Tuberculosis
Genital tuberculosis incidence in the USA has been quoted at
0.07 % [6]. Rates are much higher in developing countries and
endemic areas. Specific risk factors for exposure may suggest
indication for testing. Secondary genitourinary tuberculosis
accounts for 10–14 % of extrapulmonary tuberculosis in some
areas [7]. Although rare, acute urethritis manifests as myco-
bacterial discharge and can result in chronic stricture forma-
tion [8]. Urine polymerase chain reaction testing may be
positive for tuberculosis. Testing of a lesion itself with poly-
merase chain reaction also provides a relatively quick and
accurate method of diagnosing the disease compared to cul-
ture [9].
M. genitalium
M. genitalium is a small parasitic bacterium that lives on the
ciliated epithelial cells of the genital tract. This bacterium may
be transmitted sexually. Its role and significance in genital
infection is still being investigated. A recent review found that
M. genitalium may have a worldwide prevalence of 2 % even
in low-risk populations [10•]. Its presence has a positive
association with urethritis, vaginal discharge, signs of cervi-
citis, and, importantly, pelvic inflammatory disease and infer-
tility [10•, 11]. The bacterium is detected by nucleic acid
amplification tests on urine sample or vaginal swab, which
may not be available in all locations. Persons found to be
infected can be treated with azithromycin 1 g once. Failure
rates of up to 28 % have been reported due to resistance [12].
Extended 5-day regimens of azithromycin therapy increase
cure rates to 96 % after doxycycline treatment failure [13]. If
treatment with azithromycin fails, prescribers should use
moxifloxacin 400 mg daily for 10–14 days.
Ureaplasma
Ureaplasma urealyticum and Ureaplasma parvum are other
potential causes of urethritis. The bacteria are actually com-
mon colonizing species of the male and female genitourinary
tract, and their role in pathologic infection is being investigat-
ed [14]. There is growing evidence for the role of particularly
U. parvum in pathologic infections; however, current recom-
mendations regarding the role of treatment are lacking [13].
The bacteria can be detected by a polymerase chain reaction
assay on voided urine or vaginal swab in women. Treatment
options follow regimens for Chlamydia, using azithromycin
or doxycycline.
Polymerase Chain Reaction Testing
Most labs offer PCR testing for M. genitalium and
Ureaplasma species on urine and vaginal swab. These are
Curr Bladder Dysfunct Rep (2014) 9:181–187
not FDA-approved at the present time but are laboratory-
validated. PCR for Gonococcus, Chlamydia, Trichomonas,
HSV-1 and HSV-2, and Mycobacterium tuberculosis is
FDA-approved (www.fda.gov).
Vulvar Conditions
Vaginal Atrophy
Vaginal atrophy is a prevalent and underreported condition in
postmenopausal women [15]. Vaginal dryness is also possible
secondary to oral contraceptive use, and vaginal atrophy has
been seen to some degree in young women on hormonal
contraceptives [16, 17]. Other causes of decreased estrogen
levels include decreased ovarian function due to radiation
therapy or chemotherapy, immune disorder, removal of the
ovaries, postpartum state, lactation, and the effects of various
medications, including tamoxifen (Nolvadex), danazol
(Danocrine), medroxyprogesterone (Provera), leuprolide
(Lupron), and nafarelin (Synarel). Previous studies have dem-
onstrated the presence of estrogen receptors throughout the
genitourinary system including not only the vagina and vulva
but also the urethra and bladder [18]. Decreased estrogens can
have a profound effect on the genitourinary system due to its
impact on cellular maturation, pH, blood flow, and nerve
stabilization. Atrophy and the resulting syndrome are typically
characterized by vaginal irritation, dryness, urinary frequency,
urgency, urge incontinence, and recurrent urinary tract infec-
tions [19]. Physical exam may reveal thinned, sometimes
erythematous tissues on physical exam. There can be a burn-
ing sensation with touching or manipulation. Age and hor-
monal manipulation precedes the onset of symptoms. Vulvar
atrophy can also be seen on biopsy; however, this would only
be performed to rule out malignancy or lichen sclerosus.
Treatment involves application of vaginal estrogens—creams
are more likely to coat the vulva and urethra than pellets or
rings. The patient can be advised to apply with the finger in
addition to the internal applicator to ensure the urethra and
vulva are covered. The commercial products can have an
alcohol base. If the patient experiences burning with the
product, compound pharmacies can mix topical estrogen with
Aloe or VersaBase® to reduce irritation. Occasionally, a peri-
menopausal or postmenopausal patient will present to the
clinic in extreme urethral pain. Once infection is ruled out, it
is the author’s experience that anticholinergics and
phenazopyridine and occasionally vaginal Valium supposito-
ries from a compound pharmacy can bridge the initiation of
vaginal estrogens for later tapering. Treating patients for atro-
phy will not only improve symptoms but may also decrease
risks for future causes of bacterial urethritis. Raz and col-
leagues demonstrated that in 93 women with postmenopausal
183
urinary tract infection randomized to treatment with
intravaginal estrogen, the estrogen decreased rates of recurrent
urinary tract infection to 0.5 episodes per patient-year com-
pared to 5.9 episodes per patient-year in the control group
[20]. Possible mechanisms of action involve improvement of
the basal maturation index, altered pH [21], and improved
mucosal seal of the urethra [22].
Infectious Vulvovaginitis
Inflammation of the vagina is often secondary to bacte-
rial vaginosis, candida infection, and/or Trichomonas. All
can present with pain, itching, and discharge. Dysuria
may be present as well and is characterized by pain from
contact of urine with the vulva externally [23]. Treatment
should be guided by the underlying cause [23]. Diagno-
sis involves testing for the causative organism. Wet
mount preparations from the vagina may reveal
Trichomonas organisms on light microscopy; however,
this has a lower sensitivity as compared to culture and
polymerase chain reaction at 65,78, and 99 %, respec-
tively. KOH wet mount taken from the lateral walls of
the vagina is useful for identifying yeast (pseudohyphae
and buds). The vaginal pH measurement, taken from just
inside the entrance to the vagina, can contribute to the
differential: bacterial vaginosis and Trichomonas infec-
tions tend to exhibit a pH above 4.5 (normal 3.8 to 4.5).
Contact Vulvovaginitis
Contact vaginitis typically presents with erythema, irritation,
and pruritus (more common in allergic reaction) [24]. Com-
mon causes include wipes, soap, cleansers/douches, filamen-
tous toilet papers, condoms, spermicide, detergent, perfumes,
lubricants, and semen. These patients can present with dysuria
from local irritative symptoms. A detailed history regarding
practices may reveal the source of irritation (for example,
residual bleach on the hands prior to onset of symptoms).
Interestingly, interstitial cystitis and a history of recurrent
urinary tract infection have been found to be more prev-
alent among subjects with contact vulvitis [25]. In our
practice, the patient with complaints of vulvar symptoms
is provided a list of irritants that worsen and substances
that reduce vulvar irritation—this reduces the interview
time in clinic and can be used as a resource at home. She
reports her triggers for documentation after she has had
time to think on the subject. This list alone (Table 1)—
particularly changing tissue products and ceasing wipes—
has resolved or improved a significant proportion of our
clinical population. For extreme cases, vaginal steroids or
wound care can be required.
184 Curr Bladder Dysfunct Rep (2014) 9:181–187

Table 1 Comprehensive list of vulvar irritants. Most importantly, the
authors provide suggested first-line remedies that often provide relief to
the patient with minimal costs
Vulvar exposures
Irritants
• Sanitary wipes
• Perfumed or harsh soaps
• Filamentous toilet papers or pads
(e.g., septic, safe, or recycled
brands)
• Vigorous wiping
• Lace or other abrasive clothing
(tight jeans)
• Horseback or bicycle riding
• Spermicidal lubricants or even
particular condom materials
• Household cleaners on hands (self
or partner)
• Feminine perfumes
• Cologne or facial hair on partner’s
face
• KY Jelly
Calming agents or habits
• Aloe-based sensitive toilet paper
• Blotting rather than wiping
• Hydrating hypoallergenic
sensitive skin soap (if allergic to
sodium laurel sulfate, African
black soap can be used)
• Cotton underwear: keep as dry as
possible
• Sanitary napkins with a plastic
rather than fibrous top
• Olive oil for comfort or
intercourse
• Coconut oil for comfort (can be
chilled)
• Petroleum jelly or other barrier
after cleaning to protect from
irritation (urine, chlorine, etc.)
some patients. Further research and work is needed to
find effective medical treatment, as treating with com-
mon pain medications and antidepressants has not shown
great success. A randomized control trial by Foster et al.
in 2010 did not show advantage in pain relief over
placebo for desipramine and lidocaine treatment [29].
Surgical excision of the involved vulvar tissue should
be considered in rare unresponsive cases and only by
experienced hands. A second opinion is prudent. Success
from vestibulectomy is reported between 65 and 90 %
but long-term relief is uncertain [30]. Multidisciplinary
approaches to treatment, including pelvic floor physical
therapy, have shown better results [31]—therefore, reduc-
ing tension in high-tension pelvic floor muscles may be
particularly helpful to reduce overall pain.
Anatomic Considerations
Diverticula

Vulvar Lichen Sclerosus
Vulvar lichen sclerosus presents as a thickening of the vulvar
skin with varying degrees of involvement. It is characterized
by pruritus, pain, and tenderness with or without blisters and
ulcers [26]. Diagnosis is by biopsy. Topical corticosteroids are
the first-line treatment for vulvar lichen sclerosus, and topical
calcineurin inhibitors remain the second-line agents in patients
for whom steroids provided incomplete resolution of symp-
toms or were not tolerated.
Vulvodynia
Vulvodynia is a diagnosis of exclusion, and care must be taken
to rule out other etiologies (including neuropathy) for pain.
Vulvodynia is generally divided into localized provoked pain
(vestibulodynia) and generalized unprovoked vulvodynia
[3••]. Vestibulodynia is defined as pain of the vestibule of
the vulva and not explained by another condition for greater
than 3 months. The prevalence is estimated to be from 11 to
16 % in a recent review by Andrews [3••]. Central and
peripheral sensitization seems to be responsible for perpetua-
tion of the symptoms long after the initial inciting event has
occurred. Possible inciting events could range from traumatic
injury (straddle injuries, overstretching of nerves to the pelvic
floor during pregnancy) to hormonal changes and to surgical
and medical side effects [27••, 28••]. Lifestyle changes may be
attempted first. The simple measures of switching to cotton
underwear, avoiding tight-fitting undergarments, using mild
soaps, lubrication for sexual intercourse, and cooling gel
packs to decrease painful sensation may provide relief for
There are anatomic etiologies to consider in women pre-
senting with symptoms of urethritis. Urethral diverticula
are rare and therefore not often considered in the differ-
ential. The overall incidence in females is between 1 and
6 % [32]. When present, they typically occur in the distal
two thirds of the urethra. Symptoms classically include
dysuria, dyspareunia, and postvoid dribbling. Symptoms
may also include a painful vaginal mass, chronic pelvic
pain, refractory lower urinary tract symptoms, obstruction
or stress urinary incontinence, intermittent passage of
purulent or bloody material, and recurrent UTIs. Patients
may also be asymptomatic with an incidentally detected
diverticulum. The diverticulum may be suspected on
physical exam by a palpable mass; urethral fluid may be
expressed and cystoscopy may reveal an ostium. MRI is
the most sensitive imaging modality with most centers
having specific protocols, including postvoiding images,
to provide the best visualization of the urethra [33]. Some
studies have found sensitivity to be up to 100 % [34]. The
use of transvaginal ultrasound in the diagnosis of diver-
ticula has been investigated and can be useful in patients
with contraindication to MRI. Furthermore, transvaginal
ultrasound may be a relatively easy and inexpensive
method of management and postsurgical follow-up [35].
Treatment is primarily surgical but observation is an op-
tion in asymptomatic or compromised patients. It should
be noted that prior transurethral bulking agents will be
read by many radiologists as a diverticulum. Correlation
with history and comparison of the density within the
structure to the urine in the bladder will help differentiate
the bulking agents from a true diverticulum.
Curr Bladder Dysfunct Rep (2014) 9:181–187
Fig. 1 Rough diagnostic guide to
be used in the work-up of non-
UTI dysuria in females. This
should be used, in conjunction
with the paper, to aid the
physician in arriving at the
appropriate diagnosis and
treatment
Skene’s Duct Cyst
The Skene’s glands are paraurethral glands located along
the anterior vaginal wall. The ducts drain into the distal
urethra near the meatus. Cyst, irritation, or abscess may
uncommonly develop. When adjacent to the urethral
meatus and large enough, they may even cause urethral
obstruction and urinary retention. They can cause dysuria
or focal pain. Physical exam may reveal an erythematous
irritation of a portion of the meatus or a small palpable
cyst. MRI or ultrasound can be useful for diagnosis.
Surgical excision may be required and is usually straight-
forward [36•].
Foreign Objects
Iatrogenic causes of urethritis should be kept in mind during
the evaluation. A thorough history and physical exam may
reveal an obstructing or eroded sling as a cause for the pa-
tient’s dysuria (due to turbulence or mucosal irritation, respec-
tively). Rarely, self-insertion of foreign bodies will be the
cause. Physical examination of the vagina and vulvar region
after a thorough history will yield the most information.
Iatrogenic injury secondary to implanted devices such as
sling, bulking agents, intrauterine devices, and pessaries
should be sought. Imaging or cystoscopy may be performed
to evaluate the extent of involvement and assess for damage to
the urethra.
185
Trauma
Urethritis is possible secondary to mechanical/chemical
trauma, such as lace or tight clothing. Passage or rarely
retention of calculi in the urethra or intramural ureter
(referred pain in the latter case) can lead to symptoms.
Trauma from normal or rough sexual intercourse may
cause local inflammation and symptoms, especially as
menopause sets in, rendering the tissue more vulnerable.
History will usually yield a potential cause; however, there
may be situations the woman does not feel comfortable
disclosing. Trauma should be suspected when edema is
observed and if the story seems inconsistent. The patient’s
limits of tolerance should not be crossed, and cystoscopy
and exam under anesthesia may be necessary.
Urethral Stricture
Urethral stricture can cause dysuria due to turbulent flow.
Although rare, urethral stricture in women may also present
with frequency, urgency, and less commonly obstructive
symptoms [37]. One of the authors evaluated a case of
Lactobacillus urethritis in a 48-year-old woman proximal to
an underlying urethral stricture, the obstruction allowing for
growth of the usually non-pathogenic organism. Report of
weak or splayed stream or uroflow revealing low flow rates
may be suggestive; however, the diagnosis is typically made
by cystoscopy.
186
Cancer
Unresolved urethritis can rarely reflect a neoplastic pro-
cess. Cystoscopy (and cytology where relevant) should
be undertaken in patients who are not responding to the
above interventions or who have microscopic hematuria
(≥3 rbc per ×40 high power field on urine microscopy) at
any point. Hematuria should prompt upper tract radio-
logic evaluation as well [38].
Conclusion
Urethritis is a common and highly symptomatic condition
affecting women at a wide range of ages. The physician who
is facile with the above work-up will provide an efficient
diagnosis and well-chosen treatment plan.
In summary, a few basic considerations at presentation
(vulvar atrophy, exposures, etc.) will often identify the cause.
Urinary tract and vaginal infection should be ruled out. Neg-
ative Chlamydia and Gonococcus testing does not necessarily
equate to a lack of infection. The microbes M. genitalium,
U. urealyticum, and U. parvum will have an important (albeit
not completely characterized) impact on how we treat sexually
transmitted infections in the future. For centers that do not
have the testing resources, treatment regimens have been
suggestive above that will cover most organisms. Herpes
and rarely tuberculosis should be considered.
The work-up beyond infection will elucidate details
pointing to vaginal conditions, trauma (sexual or other-
wise), urethral diverticulum, iatrogenic injury, and even
cancer. During the work-up, physicians should convey
validation that the pain and symptoms are real and edu-
cate the patient on the nature of empiric interventions.
As the patient waits for a diagnosis, she should have the
confidence that effective treatment options are available
and further efforts will be made to find a diagnosis
where tests and empiric trials are unrevealing. In appro-
priate cases, psychological referral should be clearly stat-
ed as a multidisciplinary adjunct to help the patient cope
with and control refractory pain, and the provider does
not think the symptoms are “in her head.”
Ultimately, the management of urethritis will be based on
the individual patient assessment (Fig. 1). A multidisciplinary
approach including physical therapy to rectify guarding reac-
tions in the pelvic floor will often improve symptom resolu-
tion in addition to treating the inciting event. Consideration of
the full differential diagnosis and adjunctive treatments will
lead to satisfactory resolution of urethritis in the majority of
patients.
Curr Bladder Dysfunct Rep (2014) 9:181–187
Compliance with Ethics Guidelines
Conflict of Interest Jeffrey Gilbert and William Ulmer declare that
they have no conflicts of interest. Elise De reports financial relationships
outside of the submitted work with the following companies: Astellas,
Allergan, American Medical Systems, AMGEN, Boston Scientific,
Ferring, Welch’s Grape Juice, Capital Region Medical Research Founda-
tion, and United BioSource Corporation.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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