Joint EMAS, IMS and ESSM response to EMA advice regarding high-strength estradiol vaginal creams
The European Medicine Agency on October 4th warned both consumers and prescribers against the use of high-strength estradiol creams for longer than 4 weeks . These high dose creams are marketed in Austria, Bulgaria, Croatia, Czech Republic, Estonia, Germany, Hungary, Latvia, Lithuania and Slovakia.
Genitourinary syndrome of menopause affects more than half of postmenopausal women. The syndrome comprises of genital, urinary and sexual symptoms, which have a significant impact on health and quality of life. While the high-strength preparations included in the EMA recommendation may increase the circulating concentrations of estradiol, those currently in use in most of Europe and worldwide provide much lower doses, with negligible effects on systemic levels. The safety of these low-dose preparations has been confirmed by many studies, which have shown no adverse effects.
Given the prevalence of genitourinary syndrome of menopause and the efficacy and safety of low-dose preparations in current use, the European Menopause and Andropause Society (EMAS), the International Menopause Society (IMS) and the European Society for Sexual Medicine (ESSM) recommend that low-dose preparations should continue to be used in women who need them.
Antonio Cano, EMAS President
Susan Davis, IMS President
Yacov Reisman – ESSM President
EMA Four-week limit for use of high-strength estradiol creams 4 October 2019 EMA/531250/2019 :
EMA’s safety committee (PRAC) has recommended limiting the use of high-strength creams containing 100 micrograms/gram (0.01%) of estradiol to a single treatment period of up to 4 weeks. This measure is intended to minimise the risk of side effects caused by estradiol absorbed into the bloodstream from creams applied inside the vagina to treat symptoms of vaginal atrophy in women who have been through menopause.
The PRAC has reviewed available data on the safety and effectiveness of high-strength estradiol-containing creams, including data on the amount of estradiol in the blood. These data showed that in postmenopausal women who had used these creams, the levels of estradiol in the blood were higher than normal postmenopausal levels. The PRAC concluded that absorption of estradiol into the bloodstream is of concern and could result in similar side effects to those seen with hormone replacement therapy (HRT). The side effects of HRT taken orally or used transdermally (as patches) include venous thromboembolism (formation of blood clots in the veins), stroke, endometrial cancer (cancer of the lining of the womb) 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.
The prescribing information for these creams will be updated with the new recommendations. A warning that the medicine is to be used for a single treatment period of up to 4 weeks only will be placed on the outer and inner packaging and the size of the tube will be limited to 25 grams to prevent use for longer than recommended.
Human medicines: regulatory information