Newer Hormone Treatments for Prostate Cancer May Raise Risk of Depression

Prostate cancer patients treated with the latest forms of hormone blockers were twice as likely to develop depression compared with men treated with older forms of hormone therapy or those who received no such medication at all, results from a new study show.

It's a risk that cancer doctors will need to keep in mind when prescribing these drugs to patients, said lead researcher Dr. Kevin Nead, an assistant professor of epidemiology at the University of Texas MD Anderson Cancer Center in Houston.

"Our study does not suggest that any men who are eligible for these medications should not be on them because of the risk of depression," he said. "What it does reinforce is that we have people who we know, because they have cancer, are already at increased risk for depression."

Putting them on these medications is potentially doubling their risk, and Nead said, depression in cancer patients is associated with worse survival.

"These are patients we need to pay a lot of attention to and try to have early interventions to prevent or treat their depression, because it will impact their overall outcomes," he said.

Prostate cancer feeds on male hormones like testosterone, which are also known as androgens. Doctors have long treated prostate cancer in part by blocking androgen, depriving cancer cells of their fuel.

They now have second-generation anti-androgen drugs like abiraterone and apalutamide that are even better at blocking testosterone than earlier medications, researchers said.

But a lack of testosterone increases a man's overall risk of depression, whether or not he has prostate cancer.

"Men with low testosterone are at an increased risk of depression," Nead said. "In men who have low testosterone, if you give them testosterone back, it actually improves their mood and decreases the risk of depression."

Cancer patients are at increased risk of depression anyway, given their battle with a deadly disease. Worse, depression tends to profoundly impact the outlook for cancer patients.

"We know depression in cancer patients is particularly bad in that it's associated with patients having worse cancer outcomes, including worse overall survival," Nead said.

Depression "might impact people's interest in being aggressive" with their cancer treatment, he added. "It might affect their overall health and how they can tolerate different therapies. It might affect their decisions on how they pursue their cancer care or how often they see their doctor."

To see how much additional risk of depression comes with the newer androgen blockers, Nead's team analyzed data from nearly 30,100 prostate cancer patients.

They broke the men into three groups -- those who received no hormone therapy, those who got the more established medications, and those treated with second-generation anti-androgen drugs.

"If you look across all three of these groups, the men that received second-generation anti-androgens had an increased risk of depression," Nead said.

The risk likely increases so dramatically because the second-generation drugs are so much more better at their job, said Dr. Bobby Liaw, clinical director of genitourinary oncology for the Mount Sinai Health System in New York City.

The older drugs "do very well in bringing your testosterone levels down, but they only stop testosterone production at the main factory of testosterone, which is the testes," Liaw explained.

"In reality, you do have some small amounts of androgen production from other places in the body that traditional hormone therapy would not shut down," he added. For example, the adrenal gland produces a small amount of male hormone, as do fat cells.

"You come along with a much more potent androgen receptor antagonist, it will further deprive cells already kind of starved for testosterone of even more of it," Liaw said. "It's not a big surprise it could worsen moods and depression."

Neither Nead nor Liaw felt that the depression risk from the newer drugs outweighs their benefits for prostate cancer patients, however.

"It's not to say that just because there's that risk of depression that we should entirely shy away from an otherwise very efficacious treatment, but I think it definitely warrants us being a little bit more cognizant," Liaw said. "We do need to be much more cognizant of these long-term side effects. We need to be more prepared to catch early signs of depression."

Family members and friends of prostate cancer patients can help by watching their loved ones as they undergo hormone therapy for signs of depression, the doctors said.

"Often times the patient themselves may not always be the best judge of it. From day to day, if it's a small change, they might not notice it," Liaw said.