Study uncovers a new mechanism explaining how chemicals affect sex hormones

Researchers at the University of Oulu have identified a previously unknown mechanism in humans that may explain why certain medicines and environmental chemicals disrupt the balance of sex hormones. The finding deepens scientific understanding of so-called endocrine disruptors—chemicals known to interfere with the body’s hormonal systems. The study is published in the journal Basic & Clinical Pharmacology & Toxicology.

At the center of the discovery is pregnane X receptor (PXR), which monitors the body’s chemical burden. PXR is best known for regulating how the liver processes medicines, but the new research shows it also influences the production of SHBG, a protein that transports sex hormones in the bloodstream. SHBG helps regulate levels of hormones such as testosterone and estrogen and determines how much of them is actually available for the body to use.

In the study, healthy volunteers were given the antibiotic rifampicin for one week. Rifampicin is one of the strongest known activators of PXR. The effect was striking: SHBG levels in the blood doubled in almost all participants. In men, total testosterone levels also rose. Experiments in liver cells revealed that rifampicin boosted SHBG production—but the effect disappeared when PXR was blocked.

According to the researchers, the discovery suggests that many everyday chemicals may influence sex hormones indirectly by increasing SHBG production through PXR activation.

“We have long known that some chemical substances can disturb the balance of sex hormones. Now we’ve identified a mechanism—a new PXR–SHBG–testosterone pathway—that explains these effects in humans,” says Professor of Internal Medicine Janne Hukkanen, who led the study at the University of Oulu.

PXR can be activated by a wide range of chemicals. These include certain medicines, compounds found in food, and many environmental chemicals such as pesticides, flame retardants and plastic additives. The researchers therefore believe the finding may have broad significance.

“Understanding this mechanism improves our ability to predict how medicines and chemical exposures in the environment may affect hormonal systems. It also helps in developing safer substances and reducing harmful effects in advance,” Hukkanen says.