Heather Jim, MD
Androgen-deprivation therapy (ADT) can be associated with significant psychological effects in patients with prostate cancer.
during the meeting, Jim, an associate member in the Health Outcomes and Behavioral Department at Moffitt Cancer Center, further described the psychological impacts of testosterone-lowering drugs for patients with prostate cancer—and what oncologists should do to help.
OncLive: What are the side effects associated with testosterone-lowering drugs?
: Testosterone-lowering drugs are associated with a whole constellation of side effects that include depression, cognitive impairment, fatigue, loss of muscle mass, and inflammation, as well as cardiovascular disease and cardiovascular mortality.
Why is depression an important side effect to address?
It is really quite astonishing, because we have done some research at Moffitt Cancer Center that suggests that after about 6 months on ADT, 40% of patients are experiencing clinically significant depressive symptoms, which is really a huge number. It is important to treat depression not only to help patients feel better, but because depression is associated with increased mortality in patients with prostate cancer.
What about concentration?
Concentration is an interesting one because there are data that suggest that ADT is associated with increased cognitive impairment over time, and particularly increased problems in visual motor skills, which is the ability to mentally represent 3-dimensional shapes in your mind and then translate that into fine motor skills—such as copying a task or creating building blocks.
We do neuropsychological testing with these patients and what we find is that, at least in our study, about 50% of men experience cognitive impairment after 1 year on ADT. There has also been data from other groups to suggest that ADT is associated with an increased risk of Alzheimer disease. Men who have been treated with ADT for at least 12 months have doubled their risk of Alzheimer disease.
In clinical practice, you must hear about “chemo brain” often. Is there a relationship between that and ADT?
Yes. It is interesting because it’s not really clear how much of cognitive impairment is due to the cancer itself versus due to therapy. We know, for example, that even patients who have been treated with chemotherapy or ADT show cognitive deficits before they even receive that treatment. Is it due to the fact that there may be some sort of systemic inflammation? We are not sure—even before there is any kind of treatment.
What about muscle mass exercise in coronary disease?
Testosterone, of course, is associated with increased muscle mass. When you eliminate testosterone from the body using ADT, then patients start to lose muscle mass. This doesn’t only include upper body strength such as grip strength, but also lower body strength as well—such as strength in their legs. Perhaps it is not surprising that patients who are treated with ADT also experience significant fatigue that increases over the first 12 months.
What we actually found is that the increases in fatigue in these patients are associated with inflammation increases in circulating inflammatory cytokines. That may be one of the mechanisms by which ADT causes fatigue.
Alzheimer disease is included as a side effect, as well?
The data are really kind of intriguing about that. As you know, there is no cure for Alzheimer disease or no real way to prevent it. At this point, it is something that just needs to be monitored in these patients.
There are things that patients can do who maybe are experiencing cognitive impairment, but not dementia. It is a less severe form of cognitive impairment. For example, they can learn kind of compensatory behavioral strategies to help sort of remember things, such as putting their keys in the same place every time. It can help normalize some of these cognitive deficits as a result of cancer treatment.
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