Lower Testosterone Levels May Be Linked to Greater Lupus Risk in Women, Study Finds

Lower testosterone levels might be the reason behind why women are at a higher risk than men of developing autoimmune diseases like lupus, new research suggests.

Using animal models, researchers observed that testosterone inhibits the survival of B-cells, which are responsible for producing the autoantibodies that attack the body’s own tissues in autoimmune diseases.

Findings were published in the study, “Testosterone is an endogenous regulator of BAFF and splenic B cell number,” in the journal Nature Communications.

In general, most autoimmune diseases affect women more frequently than men, but the disparity in systemic lupus erythematosus (SLE) is particularly high. Women are about nine times more likely to develop the disease than men.

Scientists don’t know exactly why this is the case, but this recent research provides a possible explanation. These new findings expand knowledge on the mechanisms behind lupus, and could help find better ways to fight it.

“It’s very important to understand what causes these diseases to be so much more common among women,” Åsa Tivesten, a professor and chief physician at Sahlgrenska Academy in Sweden and senior author of the study, said in a press release. “In this way, we can eventually provide better treatment for the diseases.”

Looking at several mouse models of testosterone deficiency, the researchers observed that a lack of testosterone activity led to increased numbers of B-cells in the spleen.

Further experiments indicated that the link between testosterone and B-cell proliferation was a factor called the B-cell-activating factor (BAFF), which is essential for the survival of B-cells.

“We have concluded that testosterone suppresses BAFF. If you eliminate testosterone, you get more BAFF and thereby more B cells in the spleen because they survive to a greater extent. Recognition of the link between testosterone and BAFF is completely new. No one has reported this in the past,” Tivesten said.

The connection between testosterone and BAFF was also supported by observations in human samples.

After examining blood samples from 128 healthy men, researchers saw that serum BAFF levels were higher in men with lower testosterone.

These results also agree with previous data in humans suggesting that testosterone may protect against autoimmune diseases, and that genetic variations in BAFF are linked to a higher risk of autoimmune diseases such as lupus.

The importance of BAFF in the development of lupus is well-established, since the only new treatment approved for the disease in more than 50 years — GSK’s Benlysta (belimumab) — is an add-on immunotherapy that specifically blocks BAFF.

However the therapy is only partially effective, and is indicated only for a subset of patients with active disease and autoantibodies who are receiving standard therapy.

“That’s why this information about how the body regulates the levels of BAFF is extremely important, so that we can continue to put the pieces together and try to understand which patients should have BAFF inhibitors and which should not,” Tivesten said. “Accordingly, our study serves as a basis for further research on how the medicine can be used in a better way.”