Study Reveals How Chemicals Influence Sex Hormone Balance

Scientists at the University of Oulu in Finland have identified a biological mechanism that may explain why some medicines and environmental chemicals disrupt the balance of sex hormones in the human body. The discovery improves scientific understanding of endocrine disruptors, chemicals known to interfere with the body’s hormonal systems.

The research focuses on pregnane X receptor (PXR), a molecular sensor that monitors the body’s chemical burden. PXR has long been recognized for its role in controlling how the liver processes medications. However, the new study shows that it also affects the production of sex hormone‑binding globulin (SHBG), a protein that carries sex hormones through the bloodstream. SHBG plays an important role in regulating hormones such as testosterone and estrogen because it determines how much of these hormones remains available for the body to use. 

To examine this process, the research team conducted a study involving healthy volunteers who received the antibiotic rifampicin for one week. Rifampicin is known as one of the strongest substances that activates PXR. The researchers observed a clear response: SHBG levels in the blood roughly doubled in nearly all participants. In male participants, total testosterone levels also increased during the study. 

Additional experiments were performed using liver cells to better understand the mechanism behind these changes. The results showed that rifampicin increased the production of SHBG in the cells. However, when the researchers blocked the activity of PXR, this effect no longer occurred. This finding confirmed that activation of PXR plays a central role in stimulating SHBG production.

The researchers say the results suggest that many chemicals encountered in everyday life could influence sex hormones indirectly by activating PXR and increasing SHBG levels. Because SHBG regulates how much testosterone and estrogen are available in the body, changes in its levels could alter hormone balance. 

“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, senior author of the study published in Basic & Clinical Pharmacology & Toxicology.

PXR can be activated by a wide variety of substances. These include certain medications, compounds present in food, and environmental chemicals such as pesticides, flame retardants, and plastic additives. Because these substances are common, the researchers believe the findings may have wide relevance.

“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 adds.