15 Jul Prostate Cancer: Effects of Hormone Therapy on Cognitive Function Addressed in Large Study

MedicalResearch.com Interview with:

Dr. Jayadevappa

Ravi Jayadevappa, PhD, MS
Department of Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104-2676 

MedicalResearch.com: What is the background for this study?

Response: In the US, prostate cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death among men. Research shows that hormone therapy or ADT reduces the levels of male hormones in the body, called androgens, to stop them from stimulating cancer cells to grow., and thus is effective in reducing the spread and progression of prostate cancer.

At the same time, some research has suggested that decreasing androgen levels may increase the risk factors for Alzheimer’s and dementia, including loss of lean body mass, diabetes, cardiovascular disease, and depression. The ADT therapy may lead to impaired neuron growth and the regeneration of axons, thus affecting the cognitive function. Thus there is growing interest in the possible association between exposure to ADT and cognitive dysfunction.

Our study investigates the association between exposure to ADT and subsequent diagnosis of Alzheimer’s or dementia in elderly, fee-for-service Medicare enrollees using SEER-Medicare linked databases.

MedicalResearch.com: What are the main findings? 

Response: Our study contributes to existing knowledge while also adding some unique elements. In particular, our study has three key strengths.

• The first strength is the sample size, which is one of the largest in the literature. For this retrospective study, we used data from a sample of men ages 66 years and older with localized or advanced prostate cancer who were diagnosed between 1996 and 2003. Of the 154,089 men, 62,330 (average age 76) received ADT within two years of being diagnosed with cancer, and 91,759 did not receive the treatment.
• Second strength is the length of follow up. Each patient in our cohort was followed up until 2013, so each patient potentially had at least 10 years of follow-up after their diagnosis. To our knowledge, this is one of the longest follow-up periods – if not the longest – in the literature.
• Third strength is the fact that our analysis adjusted for several key covariates and performed sensitivity analyses. Finally, we examined the associations across different doses of ADT and found that the association was stronger for men who received more doses of ADT. 

MedicalResearch.com: What should readers take away from your report? 

Response: Our population-based study spanning 10 years or more following the diagnosis of prostate cancer shows that exposure to ADT was associated with increased hazard of both Alzheimer disease and dementia among elderly fee-for-service Medicare beneficiaries with prostate cancer.

Our results suggest that clinicians need to carefully weigh the long-term risks and benefits of exposure to ADT, particularly in patients with a long life expectancy or patients who already show signs of cognitive decline. For patients with advanced prostate cancer, the potential life-prolonging benefits of ADT likely still outweigh the risks, even when considering the added risk of dementia.

However, for patients with localized prostate cancer and a long life expectancy, our study provides some of the strongest evidence to date that physicians should make their patients aware of the potential cognitive side effects associated with such therapy and perhaps opt to limit ADT exposure. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: While our study suggests an association between ADT and subsequent dementia diagnosis, we were unable to further investigate possible biological mechanisms of this association. Thus, our future research will attempt to elucidate a possible biological mechanism between exposure to ADT and development of dementia, and study this relationship prospectively. It is crucial to establish whether this association is mediated by long-term androgen suppression, especially as dual androgen blockade with second-generation antiandrogens moves earlier in the treatment course of prostate cancer. Also, we will conduct further work to characterize individuals undergoing ADT who are at high risk of developing earlier dementia. 

Citation:

Jayadevappa R, Chhatre S, Malkowicz SB, Parikh RB, Guzzo T, Wein AJ. Association Between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men With Prostate Cancer. JAMA Netw Open. Published online July 03, 20192(7):e196562. doi:10.1001/jamanetworkopen.2019.6562 

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Last Updated on July 15, 2019 by Marie Benz MD FAAD