Effect of Vaginal Estrogen on Asymptomatic Microhematuria (AMH)

This is a randomized controlled trial of vaginal estrogen cream for postmenopausal women
with microscopic hematuria (AMH). Potential subjects will be screened with a dipstick
urinalysis of a catheterized urine specimen, followed by microscopic urinalysis and urine
culture if urine dipstick is positive for trace blood or greater. Women who are identified
as having asymptomatic microscopic hematuria (>3 red blood cells (RBC) per high powered
field (hpf)) on a single urine microscopy specimen in the absence of urinary tract infection
or other benign cause will be eligible for enrollment.

Women meeting inclusion criteria will be randomized to either conjugated equine estrogen
cream (Premarin, 0.625mg conjugated estrogens) or placebo cream for 8 weeks. Microscopic
urinalysis of a catheterized urine specimen will be re-checked at 8 weeks to check for
reduction, resolution or persistence of AMH. During the 8 weeks of vaginal estrogen or
placebo, women will complete the recommended AMH workup as dictated by the American Urologic
Association (AUA) guidelines (cystourethroscopy, serum blood urea nitrogen and creatinine
levels, and computed tomography (CT) scan of the abdomen and pelvis with and without
intravenous contrast).1

Validated questionnaires to assess vaginal atrophy and symptoms of urinary urgency and
frequency will be completed at time of randomization and again at 8 weeks. Cost analysis of
the standard AMH workup (cystourethroscopy and CT scan) versus empiric treatment with 8
weeks of vaginal estrogen cream will be calculated based on Medicare reimbursement, as well
as market price for vaginal estrogen cream Additionally, patients will be asked to complete
a questionnaire to assess the level of bother associated with completing the current AMH
workup of CT scan and cystoscopy as compared to completing a treatment course of vaginal
estrogen cream.

Secondary analyses will determine whether there are additional benefits to a trial period of
vaginal estrogen cream in postmenopausal women with AMH prior to reflexively screening for
urinary tract abnormalities. We will compare the cost of a standard AMH workup to a
treatment course of vaginal estrogen cream, to determine whether vaginal estrogen with
potential resolution of AMH is associated with any savings prior to pursuing further workup.
Additionally, questionnaires will ask study participants whether they would prefer to
undergo the current AUA AMH workup or a treatment course of vaginal cream, in order to
assess bother and anxiety associated with these interventions.

Inclusion Criteria:

- Post-menopausal women

- Asymptomatic microscopic hematuria (three or more red blood cells per high powered
field on a single urine microscopy) in the absence of urinary tract infection.

Exclusion Criteria:

- Known urologic disease

- Presence of gross hematuria

- Presence of indwelling urologic foreign body (foley catheter, ureteral stent)

- Inability to obtain intravenous contrast CT scan (elevated creatinine, severe
contrast allergy)

- History of pelvic irradiation or malignancy

- Not a candidate for vaginal estrogen

- Allergy to vaginal estrogen

- Current or prior diagnosis of breast or endometrial cancer

- History of deep vein thrombosis/pulmonary embolus

- Hypercoagulable state