FRANKFURT. In the 1970s, the contraceptive pill was the most frequently used method of contraception in Western countries; in Germany, for example, one in three women used “the pill.” It is safe and reliable, covered by (most) health insurances, and – particularly in the 1960s and 1970s – was also regarded as an instrument of female self-determination.

Over time, however, a number of side effects associated with hormonal contraceptive methods became apparent, from nausea, weight gain, and breast tenderness to more serious risks such as high blood pressure, liver dysfunction, and thrombosis. Some medications, such as certain antibiotics or St. John’s wort products, can reduce the effectiveness of the pill.

The pill is increasingly rejected

Although side effects occur comparatively rarely, concerns about the risks have contributed to a declining acceptance of the pill. According to recent surveys by the German Federal Centre for Health Education, since 2023 fewer women and couples have been using the pill for contraception; among younger adults in particular, the condom has replaced the pill as the number one contraceptive method.

A research team led by Dr. Claudia Tredup and Prof. Stefan Knapp from the Institute of Pharmaceutical Chemistry at Goethe University Frankfurt, Prof. Daniel Merk from Ludwig Maximilian University of Munich, and Prof. Hubert Schorle from UKB, who is also a member of the Transdisciplinary Research Area (TRA) “Life & Health” at the University of Bonn, and Prof. Jean-Pierre Allam, Head of Andrology at UKB, is now working to develop contraceptives with particularly few side effects that do not rely on hormonal mechanisms. To this end, they have launched the PREVENT project (“Precision Reproductive and Contraceptive Target Discovery Network”) and secured three years of project funding from the German Federal Ministry of Research, Technology and Space.

Active substances for new contraceptive strategies

PREVENT project leader Dr. Claudia Tredup from the Institute of Pharmaceutical Chemistry at Goethe University Frankfurt explains: “Hormonal contraceptive methods such as the contraceptive pill interfere with the body’s natural hormone cycle. In PREVENT, we are investigating for alternative non-hormonal approaches for both women and men in order to offer couples additional contraceptive options.”

The PREVENT team’s research approach focuses on so-called small molecules that specifically block proteins found exclusively in sperm or egg cells. For example, small molecules could specifically target sperm, preventing sperm from reaching the egg cell. Tredup explains: “Since contraceptives are administered to healthy individuals, they must not only be reliable and reversible, but also safe and highly tolerable.”

Given these complex requirements, the search for suitable active substances is highly demanding. The PREVENT team will therefore develop a drug discovery platform to establish technologies and tools for validating non-hormonal contraceptive concepts. Highly selective and effective compounds – so-called “chemical probes” – will enable the targeted testing of new contraceptive strategies and provide a solid foundation for preclinical and later clinical development.

Biochemist Tredup adds: “We already know of a number of genes associated with infertility. Within the PREVENT team, we want to build the expertise needed to use the corresponding proteins as target structures for safe, non-hormonal contraceptive strategies.” She is convinced that this is not just a classic pharmaceutical research project: “With PREVENT, we are also addressing key societal goals of reproductive self-determination and global health policy.”