ADT Increases Risk for Depression in Elderly Men With Localized Prostate Cancer


Although androgen deprivation therapy (ADT) has a survival benefit for patients with high-risk and locally advanced prostate cancer, it is associated with substantial safety concerns, and mixed data exist regarding whether ADT causes clinically significant depression.

Frank delaRama, RN, MSN, AOCNS

Frank delaRama, RN, MSN, AOCNS

Frank delaRama, RN, MSN, AOCNS

Although androgen deprivation therapy (ADT) has a survival benefit for patients with high-risk and locally advanced prostate cancer, it is associated with substantial safety concerns, and mixed data exist regarding whether ADT causes clinically significant depression. A new population-based study published online April 11, 2016 in the Journal of Clinical Oncology sought to explore this possible association.1

Using the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database from 1992 to 2006, researchers identified a total of 78,552 men aged ≥65 years with stage I-III prostate cancer, of whom 33,882 (43%) received ADT within 6 months of diagnosis.

Patients with a psychiatric diagnosis in the prior year were excluded.

The association between pharmacologic ADT and diagnosis of depression (primary endpoint) or receipt of psychiatric treatment (secondary endpoint) was analyzed using Cox proportional hazards regression. An additional secondary analysis explored the association between duration of ADT and the diagnosis of depression or receipt of psychiatric treatment.

Adjusted Cox analyses demonstrated significantly increased risks for depression (23%) and inpatient psychiatric treatment (29%) among patients receiving ADT, and a nonsignificant 7% increased risk of outpatient psychiatric treatment.

All three of these parameters demonstrated a significantly increased risk with duration of ADT. For example, the risk of depression rose from 12% with ≤6 months of treatment, to 26% with 7 to 11 months of treatment, to 37% with ≥12 months of treatment.

"We know that patients on hormone therapy often experience decreased sexual function, weight gain and have less energy—many factors that could lead to depression. After taking a deeper look, we discovered a significant association between men being treated with ADT for PCa and depression," noted senior author Paul Nguyen, MD, of Brigham and Women's Hospital, in a statement.

Nguyen added that the findings call for greater awareness of this under-recognized problem not only among patients, but also for clinicians, who need to be aware of the risk in order to recognize signs of depression and refer their patients to appropriate care.

Study authors wrote that these findings add to accumulating evidence around the major adverse event profile associated with ADT, and that the risk of psychiatric illness should be noted as a potential side effect when discussing ADT with patients. The possible adverse event also should be factored in when weighing the benefits and harms of ADT use in older men with intermediate-risk disease.

One study limitation noted by the researchers is that use of Medicare SEER data limited the scope to men aged ≥66 years at diagnosis, and thus, the results may not be applicable to younger men. Additionally, the relationship between depression and ADT treatment may be confounded by the fact that patients were older and had more comorbidity.

The researchers encouraged future studies focusing on interventions that could successfully reduce this risk and to examine whether particular subpopulations are at a higher risk, such as patients with a history of depression.

Nurse Perspective: Frank delaRama, RN, MSN, AOCNS

“Possible side effects may include …” In oncology nursing practice, we probably have uttered these five words several times daily, in our interactions with cancer patients and their families. Teaching our patients about what to expect is one of our most valuable roles in nursing. With some treatments, the side effects can be quantitatively measured, for example, blood counts and vital signs. Other side effects can be found with physical assessment, such as skin rashes or mouth sores.

Some treatments, such as androgen deprivation therapy (ADT), have adverse effects that can be difficult to measure, and have wide variations from patient to patient. In their principles of ADT, the NCCN outlines what we should be monitoring for in our patients undergoing hormone therapy:

“ADT has a variety of adverse side effects including hot flashes, loss of libido and erectile dysfunction, shrinkage of penis and testicles, loss of muscle mass and strength, fatigue, depression, hair loss, osteoporosis, greater incidence of clinical fractures, obesity, insulin resistance, alterations in lipids, and greater risk for diabetes and cardiovascular disease.”2

Reading that one sentence is pretty intimidating! If given a choice, I would like to avoid that treatment if I can. Unfortunately, for most of our cancer patients, they do not have the luxury of that choice, but must undergo ADT as part of a treatment plan prescribed to them. Given the very personal nature of these side effects, including depression, loss of libido, and erectile dysfunction, it can be difficult to complete a nursing assessment in this arena. Patients can be hesitant to share this information, and nurses and other healthcare providers may even avoid the subject to some degree.

Knowing that research, such as the study presented here, is beginning to make some concrete connections between specific cancer treatments and the risk for depression, nurses can begin to systematically address these potentially under-assessed adverse effects. The intervention could be as simple as privately asking a few questions, allowing ample time to actively listen and provide counsel and support. Since most men on ADT are regularly coming into our clinics every few months for PSA checks or ADT injections, nurses have the opportunity to regularly monitor these men at risk. Just ask them.


  • Dinh KT, Reznor G, Muralidhar V, et al. Association of androgen deprivation therapy with depression in localized prostate cancer [published online before print April 11, 2016]. J Clin Oncol.
  • National Comprehensive Cancer Network. (2016). NCCN guidelines, version 2.2016: Prostate cancer.

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