The article, entitled "Estetrol/drospirenone versus 17α-ethinylestradiol/drospirenone: An extended one generation test to evaluate the endocrine disruption potential on zebrafish (Danio rerio)", is the result of a collaboration with Mithra, a Belgian biotech company committed to transforming women's health with innovative alternatives particularly in contraception, funded by SPW Research for three years.

Conventional oral contraceptives mainly contain two components: ethinylestradiol, a synthetic estrogen, and drospirenone, a progestin. For over 30 years, ethinylestradiol has been recognized as an endocrine and environmental disruptor. Studies carried out in the 90s, testing waters upstream and downstream of wastewater treatment plants, showed that downstream fish were predominantly female, attributing these endocrine changes to ethinylestradiol. In the 1960s, a fourth natural estrogen, estetrol, was discovered in humans, produced by the fetal liver during pregnancy.

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Identified as an alternative to synthetic estrogen, Mithra has acquired a patent for its synthesis and is using it in a new contraceptive pill in combination with drospirenone. The study aims to assess the environmental impact of esterol, an alternative to ethinyl estradiol, by exposing several generations of zebrafish to environmental doses. These fish, native to India and Malaysia, are often used in aquariums and laboratories.

Analyse de Patrick Kestemont
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Patrick Kestemont

The advantage of zebrafish is that their life cycle is short; after 3-5 months, we already have a new generation of fish capable of reproducing.

Patrick Kestemont Director of the Environmental and Evolutionary Biology Research Unit (URBE) at UNamur

The results, demonstrated through validated OECD tests show a very significantly lower environmental impact of esterol than ethinylestradiol, even at much higher concentrations. This research is in line with the objectives of the European Greendeal, which calls, among other things, for pharmaceutical companies to allocate increasing attention to the environmental impact of their products, whether in terms of formulation, manufacturing processes or even the residues associated with their use.

These promising initial results were presented recently in Bilbao at the European Society of Contraception and Reproductive Health conference.