due to termination of ISR by PI with agreement by grant sponsor

Urinary tract infections (UTIs) are bothersome and more likely to occur in postmenopausal women. Frequent UTIs, as well as other problems with the urinary and genital systems such as painful sex and urinary frequency/urgency, are part of a symptom complex called genitourinary syndrome of menopause (GSM). Prasterone (Intrarosa®) is a man-made steroid that helps with painful sex in postmenopausal women. Because previous studies have shown prasterone to help with other GSM problems, this study was designed to investigate if prasterone used in the vagina decreases the number of UTIs in postmenopausal women.

Urinary tract infections (UTIs) are costly contributing to more than 8 million ambulatory visits (84% women) in the United States in 2007. Recurrent urinary tract infections (rUTIs) are UTIs diagnosed on at least 2 urine cultures in 6 months, or at least 3 in 1 year. The incidence of rUTIs increases in menopause with an estimated 10-15% of women > 60 years old having rUTIs. rUTIs contribute to a constellation of bothersome genitourinary symptoms in some postmenopausal women called genitourinary syndrome of menopause (GSM). Thus, menopause, rUTIs, and GSM are intimately linked.

Prasterone (Intrarosa®) is a synthetic version of the steroid, dehydroepiandrosterone (DHEA), approved by the US Food and Drug Administration in 2016 for the treatment of moderate to severe dyspareunia due to GSM. Large, prospective studies have shown prasterone to safely decrease vaginal pH, decrease parabasal cells, increase superficial cells, and decrease symptoms related to atrophy like dyspareunia in women with GSM. Given prasterone's favorable treatment effects on some GSM symptoms, investigation of prasterone as a possible treatment option for rUTIs in the setting of GSM is warranted.

This is a single center, double-blind, placebo-controlled, randomized trial comparing the efficacy of nightly intravaginal prasterone for 24 weeks to intravaginal placebo in decreasing rUTIs in women with GSM. The study hypothesis is that intravaginal prasterone decreases UTI incidence in women with GSM compared to placebo.

Inclusion Criteria:

• Women aged 18 years or older who are ≥ 1 year after spontaneous or surgical (bilateral oophorectomy) menopause
• Presence of ≤ 5% of superficial cells on vaginal smear and vaginal pH > 5.0
• History of ≥ 2 UTIs in 6 months or ≥ 3 UTIs in 12 months (with documentation of a UTI confirmed on urine culture within the past 1 year)
• Negative urine culture prior to treatment randomization

Exclusion Criteria:

• Known allergy/hypersensitivity to prasterone or its constituents
• Contraindications to estrogen: acute thrombophlebitis, history of blood clotting disorder, and/or personal history of thromboembolic disorder associated with estrogen use
• Known or suspected estrogen-dependent neoplasms or mammary, ovarian, cervical, or vaginal malignancies
• Known congenital urologic or gynecologic abnormality
• Chronic immunosuppression
• Need for chronic catheterization
• Vaginal bleeding of origin other than vaginal mucosal atrophy
• Vaginal infection requiring treatment
• Use of systemic hormone replacement therapy or estrogen within past 6 months
• Use of topical estrogen within past 3 months
• Consistent use of vaginal products (lubricants, douches)
• Ongoing antibiotic treatment
• Ongoing treatment with Lactobacillus
• Inability to comply with protocol or place vaginal insert with applicator appropriately
• Less than 3 months status post urinary incontinence and/or pelvic organ prolapse surgery
• Unable to speak or read English
• If an exclusion condition is resolved, the patient may be re-approached later for study recruitment (ie., genitourinary infection, use of antibiotics, etc)

De-identified raw data and other supporting materials will be made available to approved investigators. Email requests to olivia.cardenas-trowers@louisville.edu.

Data will be available beginning 1 month and ending 24 months following article publication.

Available to investigators whose proposed use of the data is for individual participant data meta-analysis and has been approved by an independent review committee for this purpose. To gain access, data requestors will need to sign a data access agreement.