Estradiol-containing (0.01% w/w) medicinal products for topical use

New review of risks with high-strength estradiol-containing creams

EMA has started a new review of high-strength estradiol-containing creams (0.01% w/w) that are used inside the vagina for treating women with vaginal atrophy who have been through menopause.

The review will assess the risk of estradiol being absorbed systemically (throughout the body) from these creams. Systemic absorption is of concern because it may result in similar side effects to those associated with the use of estradiol in systemic hormone replacement therapy (HRT), which include venous thromboembolism (formation of blood clots in the veins), stroke and endometrial cancer (cancer of the lining of the womb).

In 2014, EMA completed a review of the risk of systemic absorption with high-strength estradiol creams and recommended measures to minimise it, including limiting the use of the creams to a maximum duration of 4 weeks. However, in March 2019 the EU Court of Justice partially annulled the conclusions of the review on procedural grounds. Although the Court of Justice did not question the scientific conclusions, the partial annulment means that some of the measures taken to minimise the risk have been invalidated.

The European Commission has therefore asked EMA to reassess this risk, taking into account both the original data and any new data that have become available since the previous review, and to recommend measures that should be put in place to protect patients. The review will be carried out by EMA’s safety committee (PRAC).

While the review is ongoing, women who have any questions or concerns about their treatment should speak to their doctor or pharmacist.