Are ADT’s Side Effects Inevitable? 

Androgen deprivation therapy (ADT) is a double-edged sword.  It can do a lot of good:  in men with high-risk prostate cancer, for example, a two-year course of ADT can make the cancer more susceptible to radiation treatment, leading to a cure.  And in men with cancer that has spread beyond the prostate, ADT by itself or combined with other treatment can keep cancer at bay for years.

            But ADT can also cause health problems.  It can raise your risk of metabolic syndrome, diabetes, heart attack, stroke, cognitive impairment, loss of muscle mass, fractures, balance issues, and falling.

Now here’s the question:  Are these problems inevitable?  And the answer is:  We don’t know yet!  The Prostate Cancer Foundation (PCF) is funding efforts to help predict who is at higher risk.  What we do know is that you can fight ADT’s negative effects on your body.  With a PCF Challenge Award, a team of Harvard and Dana-Farber investigators led by Christina Dieli-Conwright, Ph.D., M.P.H., is leading a study to find out more:  the FIERCE trial (Debunking the Frailty-SarcopenIa-ADT Axis in MEtastatic Prostate CanceR with MultiComponent Exercise).

Fierce is what Dieli-Conwright, an expert in exercise oncology, would like you to be – and against ADT, a major way to be fierce is with exercise.   “Debunking” is an interesting word choice for the study’s title.  What kinds of things get debunked?  False or exaggerated claims; in this case, the claims of what is sure to happen with ADT.

I recently interviewed Dieli-Conwright about this award.  She is one of my favorite scientists in the field of prostate cancer because of her can-do spirit.  (If you missed this post on her DIY home fitness plan, it’s worth a read.  It’s got exercises anyone can do, anywhere!)  “The effects of exercise have been vastly understudied in men with metastatic prostate cancer,” Dieli-Conwright says, “particularly on how exercise can help prevent frailty and sarcopenia” (loss of muscle mass, strength, and function).  It also can help prevent metabolic syndrome, a precursor to diabetes and heart disease, and this is terribly important for overall health and quality of life – affecting the entire body, not just the bones and muscles.”

            There is a domino effect in ADT, and it starts with weight gain and metabolic syndrome.   ADT takes away testosterone, and without testosterone, your body is more likely to have higher blood pressure, higher blood sugar, more body fat around the waist, and higher levels of cholesterol and triglycerides.  All of these conditions, in turn, raise the risk of comorbid conditions such as heart disease, stroke, and diabetes.  These conditions can be debilitating on their own, and they also can create or encourage a pro-inflammatory environment that promotes the growth of cancer.

Dieli-Conwright has spent her career working to determine the underlying physiologic mechanisms by which obesity, sarcopenia, and metabolic changes affect recurrence of cancer, then coming up with and testing exercise interventions to fight obesity, diabetes, and cardiovascular disease among cancer surivors.  The goal in going after these simultaneous diseases is not only to prolong life in cancer survivors, but to improve it.

In the FIERCE study, men with metastatic prostate cancer who are receiving ADT will undergo a 16-week supervised exercise intervention (including resistance, aerobic, and functional training to improve balance and movement).  Men in the control group will undergo a stretching program and will be offered the exercise program after the 16 weeks.  The investigators will measure the effects on frailty and sarcopenia in both groups, and measure biomarkers of inflammation, muscle activity, and cancer response.  “We hope this study will establish an exercise treatment program to prevent the degenerative effects of ADT and significantly improve quality of life and outcomes in men with metastatic prostate cancer,” says Dieli-Conwright.

So:  exercise, in fighting metabolic syndrome, can help prevent other potentially serious conditions, and may help slow the growth of cancer, as well.  It even improves the cognitive effects of ADT, helping you think and function better.  Also, it can help keep you from losing bone density and muscle mass – and this, in turn, can help prevent falls and fractures.

Note: For more information on the FIERCE trial, call 877-DF-TRIAL (877-338-7425).

In addition to the book, I have written about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org.  The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  I firmly believe that knowledge is power.  Saving your life may start with you going to the doctor and knowing the right questions to ask.  I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease.  Many doctors don’t do this, so it’s up to you to ask for it.

©Janet Farrar Worthington