Last reviewed: March 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)’s 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.[33]

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 therapy (HT). 

The side effects of HT 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 HT. Other vaginal estrogen formulations are available and may be preferred. 

See Management: approach

See Management: treatment algorithm

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History and exam

Key diagnostic factors

  • amenorrhea
  • irregular menstrual cycle
  • hot flashes and night sweats
  • vaginal symptoms
  • mood changes

Other diagnostic factors

  • sleep disturbance
  • mild memory impairment
  • menorrhagia

Risk factors

  • age 40 to 60 years
  • cancer treatment
  • smoking
  • ovarian surgery
  • mother's age at menopause

Diagnostic investigations

Treatment algorithm


Clinical Director Women and Sexual Health

NHS Dumfries and Galloway

Dumfries and Galloway Royal Infirmary




HC declares that she has received sponsorship, educational grants, speaker fees, funding for attendance at meetings, and advisory board fees from several pharmaceutical and non-pharmaceutical companies, which supports the running and development of Menopause Matters Ltd.

Consultant Gynaecologist

Clinical Lead for Menopause Service

King's College Hospital NHS Trust




HH declares that he has acted in an advisory capacity for Bayer. HH received a research grant to support a clinical trial and support to attend academic conferences from Besins.

Independence Park Medical Services




BWF is a consultant for Advance Medical and Kevin Trangle Associates and is on the Speakers Bureau for Abbvie.

Dr Heather Currie, Dr Haitham Hamoda, and Dr Bradford W. Fenton would like to gratefully acknowledge Dr Rebekah Wang-Cheng, a previous contributor to this topic.

Peer reviewersVIEW ALL

Assistant Professor

Department of Obstetrics and Gynecology

Virginia Commonwealth University




NGOC declares that she has no competing interests.


Daniel Island



CS declares that she has no competing interests.


Honorary Senior Lecturer and Clinical Director

Department of Obstetrics and Gynaecology

Norfolk and Norwich University Hospital




EM declares that he has no competing interests.

Professor of Medicine and Obstetrics & Gynecology

Obstetrics and Gynecology

Columbia University in New York Medical Center

New York



MW has received research funding from Ferring and Pfizer Wyeth; has acted as an advisory board consultant for Pfizer Wyeth, QuatRx, and Yoplait; and is on the speakers' bureau of Amgen, Upsher Smith, and Warner Chilcott. MW is also an author of a reference cited in this topic.

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