Androgens Responsible for Higher Bladder Cancer Cases Among Men

Men are more susceptible to having most forms of cancer. Now, researchers have found that hormones may explain this phenomenon.

Cancer

In a new study published in the journal Science Immunology, scientists report that male sex hormones inhibit the ability of the body to fight cancer. They say this may explain why men have cancers and deadly diseases more.

Male sex hormones, also called androgens, are substances that mainly regulate the development and maintenance of masculine traits and male reproductive function.

“Historically, it was thought males may have higher cancer rates because they are more likely to engage in behaviors that predispose them to cancer, such as smoking,” stated senior study author Xue Li, Ph.D., a Cedars-Sinai Medical Center research scientist. “We observed that biology of sex, not just behavior, is an important factor in cancer development.”

Bladder cancer, in particular, is more common among males. Men have about three to five times higher probability of having the disorder, compared to women, as per research.

The findings could lead to a big leap in understanding the disparities between males and females in terms of the incidence, prognosis, and treatment of cancer.

Androgen-fueled tumors

Researchers in this study used a mouse model of bladder cancer for their inquiry. The model mimicked what is seen in humans with this condition – the growth of more aggressive tumors.

The team carried out experiments that involved the removal of different immune cells in male and female mice. Disparities in cancer severity vanished between sexes when the scientists got rid of CD8⁺ T cells.

Researchers noted that androgens constrain a man’s adaptive immune system. The body relies on this system to build immunity against pathogens that it had been subjected to in the past.

According to the research team, male sex hormones appear to interfere with CD8⁺ T cells – which are supposed to help to get rid of tumor cells. This may contribute to observed sex disparities in cases of bladder cancer.

Li’s team also observed more aggressive tumor growth in mice that had elevated androgen levels.

Improving treatment results in male patients

Researchers went further to carry out genetic sequencing of tumor CD8⁺ T cells. What they found was even more astonishing: CD8⁺ T cells in male mice displayed greater signs of fatigue and dysfunction. These were believed to be effects of androgen activity.

This finding probably shows – at least, in part – why male patients do not respond as well to immunotherapy as females. Androgens seem to render CD8⁺ T cells impotent against cancer cells.

“T cells are like soldiers commissioned to kill tumor cells. However, they can become exhausted, so immunotherapy is used to rejuvenate them,” Li explained. “Unfortunately, many cancer patients do not respond to immunotherapy.”

Findings suggest that male patients may get more help from a combination of immunotherapy and androgen deprivation therapy. The latter treatment, a common one for prostate cancer, aided immunotherapy to yield better results. It was found to help reduce the size of bladder tumors in male mice.

Researchers noted, however, that hormone therapy will work best when given early in the development of bladder cancer.