Last reviewed: February 2020
Last updated: October  2019
30 Oct 2019

EMA’s safety committee recommends a 4-week limit for use of high-strength estradiol creams

The European Medicines Agency (EMA) pharmacovigilance risk assessment committee (PRAC) has recommended limiting the use of high-strength estradiol vaginal creams (containing 100 micrograms/g or 0.01%) to a single treatment period of up to 4 weeks.[52]

The PRAC review concluded that in postmenopausal women who had used these creams, the levels of estradiol in the blood were higher than normal postmenopausal levels and could result in similar side effects to those seen with systemic (oral or transdermal) hormone replacement therapy (HRT).

The side effects of HRT include venous thromboembolism, stroke, endometrial cancer, and breast cancer.

In the absence of safety data for long-term use of high-strength estradiol creams, the PRAC recommended that these creams should only be used for a single treatment period of a maximum of 4 weeks. This formulation should not be used in patients already on hormone replacement therapy. Other vaginal estrogen formulations are available and may be preferred.

Treatment of recurrent UTI in postmenopausal women includes use of vaginally applied estrogen therapy to restore the normal vaginal flora and reduce the risk of vaginal colonisation by Escherichia coli.[53] Vaginally applied estrogen therapy demonstrated a decreased incidence and longer time to recurrence of UTI in hypo-estrogenic women.[54] However, its use is inferior to continuous antibiotic suppression in prevention of UTIs.[55]

See Management: approach

See Management: treatment algorithm

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History and exam

Key diagnostic factors

  • dysuria
  • urinary frequency
  • hematuria
  • back/flank pain
  • costovertebral angle tenderness
  • fever

Other diagnostic factors

  • urinary urgency
  • suprapubic pain and tenderness

Risk factors

  • sexual activity
  • spermicide use
  • postmenopause
  • positive family history of UTIs
  • history of recurrent UTI
  • presence of a foreign body
  • insulin-treated diabetes
  • high lifetime number of UTIs
  • recent antibiotics
  • poor bladder emptying
  • increasing age

Diagnostic investigations

1st investigations to order

  • urine dipstick
  • urine microscopy
  • urine culture and sensitivity
More 1st investigations to order

Investigations to consider

  • postvoid residual (PVR)
  • renal ultrasound
  • abdominal/pelvic CT scan
  • cystoscopy
More investigations to consider

Treatment algorithm


Una J. Lee

Female Pelvic Medicine and Reconstructive Surgery

Section of Urology and Renal Transplantation

Virginia Mason Medical Center




UJL declares that she has no competing interests.

Dr Una J. Lee would like to gratefully acknowledge Dr Elliot Blau for his contribution to this monograph, and Dr Bhavin N. Patel and Dr Howard B. Goldman, previous contributors to this topic.

Peer reviewersVIEW ALL

Associate Staff

Cleveland Clinic Foundation




PS declares that she has no competing interests.

Associate Residency Director

Texas Tech University Health Sciences Center




TJB declares that he has no competing interests.

Professor of Primary Care Research

Community Clinical Sciences Division

University of Southampton




PL declares that he has no competing interests.

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