Pharmaceutical disruption of steroidogenesis

Guillaume Ollitrault; Munkboel Cecilie Hurup; Karine Audouze; Johannsen Malene Louise; Rehman Zakariya Ur; Rene Jorgensen; Olivier Taboureau; Bjarne Styrishave; David Kristensen

doi:10.1530/endoabs.110.EP1312

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Endocrine Abstracts (2025) 110 EP1312 | DOI: 10.1530/endoabs.110.EP1312

ECEESPE2025 ePoster Presentations Reproductive and Developmental Endocrinology (128 abstracts)

Pharmaceutical disruption of steroidogenesis

Guillaume Ollitrault ¹ , Cecilie Hurup Munkboel ² , Karine Audouze ³ , Malene Louise Johannsen ⁴ , Zakariya Ur Rehman ² , René Jørgensen ⁵ , Olivier Taboureau ¹ , Bjarne Styrishave ² & David Kristensen ⁶

Author affiliations

¹Inserm U1133, CNRS UMR 8251, Université Paris Cité, Paris, France; ²University of Copenhagen, Copenhagen, Denmark; ³Inserm U1133, CNRS UMR 8251, Université Paris Cité, Paris, France, Paris, France; ⁴Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; ⁵Roskilde University, Copenhagen, Denmark; ⁶Roskilde University/Copenhagen University Hospital - Rigshospitalet, Roskilde, Denmark

JOINT3348

Concern has been raised over negative endocrine side-effects of synthetic chemicals, as active pharmaceutical ingredients (APIs), on the health of humans. While studies have investigated side-effects of APIs in humans and animals, these employed different analytical methods, measured different endpoints, investigated only one or few APIs together and often overlooked their direct effect on hormonal production. This makes it difficult to assess the scale of the problem that APIs might have on endocrinology. Additionally, comparing existing data from different studies is often challenging due to differences in analytical methodologies, such as hormone quantification techniques or the use of different model systems. Here, we present findings from a comprehensive investigation on the effects of APIs on human steroidogenesis, the quintessential hormonal pathway at the center of endocrinology. We examined the effects of 70 APIs, representing all major pharmaceutical classes used worldwide, on 16 hormones involved in steroidogenesis at physiological relevant concentrations. Our analysis identified five distinct clusters of APIs based on their effects on steroidogenesis, with only 17 APIs showing no impact. The initial enzyme in steroidogenesis, CYP11A1, was identified as the most concerning target due to its promiscuity in binding lipophilic and nitrogen-rich compounds, including prevalent pharmaceutical classes such as fungicides, antidepressants, antibiotics, and lipid-lowering statins. As pharmaceutical use continues to rise and environmental pollution with APIs becomes more pervasive, these findings show that APIs might pose a significant threat to humans through the disruption of steroidogenesis at physiological relevant doses.