Depression is linked to lowered testosterone, stress and poor sleep patterns; the new generation of androgen antagonists such as Abiraterone and Enzalutamide can make this worse, also reducing outcomes and survival.
Depression and stress are common in patients with cancer. Simply being diagnosed with cancer is known to be enough to put up levels of stress and depression. And both are linked to poorer survival.
UCLA’s Stress Management Center has reported on numerous occasions that Stress Management is the most neglected area of cancer treatment. Stress can lead to increases in cortisol, which can turn on Cox-2 pathways and cause inflammation throughout the body fueling cancer metastasis. We also know that the stress hormone norepinephrine causes prostate cancer cells to grow and migrate in men (1). We have previously also covered this with breast cancer and stress.
Depression is more complex. We know, for example, that chemotherapy drugs and antibiotics can lower levels of commensal (good) gut bacteria, some of which produce Serotonin, the 'happy hormone'. The loss of these bacteria can lead to depression.
We also know that depression can lead to poor sleep patterns, and poor sleep is linked to more depression. It can be a downward spiral.
But with prostate patients, depression can be a major issue. We know that lowered testosterone per se is linked to depression. This is not helped by the anti-androgen drugs. An androgen is a steroid that regulates male functions in the body. So, providing anti-androgens lowers testosterone and libido, increasing anhedonia and erectile dysfunction. And depression levels (2).
Now scientists are warning about the significant depression effects of the new breed of testosterone-lowering drugs, for example, Abiraterone and Enzalutamide, Bicalutamide and Apalutamide. Whereas old testosterone-lowering drugs affected production of testosterone in the testes, the new drugs block androgen receptors and thus production from other sites too, such as fat stores and the adrenals. Lowering testosterone is known to result in depression, this almost total cut makes matters far worse.
The new study (3) set out to discover how bad the problem might be. One of the researchers, Dr. Kevin Nead, an assistant professor of epidemiology at the University of Texas, MD Anderson Cancer Center in Houston said that putting men on these new medications doubles their risk of depression. Even more worrying is that depression is associated with worse cancer outcomes and worse survival rates.
The research showed clearly that using second-generation androgen antagonists is associated with a clinically significant 2-fold increased risk of depression when compared with traditional Hormone Therapy alone or to having no hormone Therapy drugs.
Researchers concluded that Medical Staff and family members should be alert to this.
Go to: New Standard of Care in Prostate cancer - Abiraterone and Prednisolone
Go to: The Dangers of poor sleep - Sleep and depression
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References
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The stress hormone norepinephrine increases migration of prostate cancer cells in vitro and in vivo; Int J Oncol, 2015 Aug;47(2):527-34; Antonio Barberi et al - https://pubmed.ncbi.nlm.nih.gov/26058426/#affiliation-1
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Depression and prostate cancer: implications for urologists and oncologists; Nature, July 30, 2020, Christopher F. Sharpley, David R. H. Christie & Vicki Bitsika - https://www.nature.com/articles/s41585-020-0354-4
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Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer; JAMA Network Open; Malgorzata K. Nowakowska, BS1; Xiudong Lei, PhD2; Mackenzie R. Wehner, MD, MPhil2,3; et al - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787430