Hormone Therapy Affects Mental Function

Androgen deprivation therapy (ADT) is a treatment for prostate cancer that has spread outside the gland. It is also called hormone therapy or chemical castration. The purpose of ADT is to reduce the production of male hormones, especially testosterone, which has the effect of temporarily halting the ability of prostate cancer cells to multiply and spread further. It is not curative, but when properly prescribed and monitored, it adds years to life expectancy. Eventually, the cancer “outsmarts” this strategy, and when that occurs it is called hormone refractory prostate cancer. Generally, patients will then begin a course of chemotherapy.

A significant problem with going on ADT is the side effects. These mainly include reduced sex drive, impotence, hot flashes, breast tenderness and growth of breast tissue, osteoporosis, weight gain, fatigue, loss of muscle mass, and depression. A less talked-about side effect is loss of mental clarity. A new study, however, confirms that this is a risk—and that patients with a specific gene mutation are even more likely to experience this problem.

The research team from the University of South Florida (Tampa, FL) was led by Brian Gonzalez from Tampa’s Moffitt Cancer Center.[i] The study involved 58 advanced prostate cancer patients who were compared with 84 post-prostatectomy patients and 88 men who did not have prostate cancer. The 58 advanced prostate cancer patients were evaluated for mental function before they began ADT; they were evaluated twice more, once at 6 months and again at 12 months after beginning ADT. The team found that those on ADT experienced greater mental fuzziness than the men in the comparison groups. Of particular concern was the finding that patients with the gene mutation called rs1047776 were at greater risk of impaired thinking—for them, the risk is 14 times greater.

Just because a correlation has been observed does not mean we can conclude it is cause-and-effect. More work is needed, including large randomized studies. However, patients should be told that reduced mental function is a risk on being on ADT, and the effect can last as long as a year.

ADT is often prescribed for prostate cancer patients who have a rising PSA after radiation treatment. This is called biochemical failure. It is assumed that the cancer has returned because either the radiation didn’t get it all, or the cancer had already left the gland at the time of treatment. Before the advent of multiparametric MRI (mpMRI), patients were typically diagnosed by means of TRUS biopsy, a bone scan and a CT scan to locate where the cancer was growing. In many cases, these men were simply put on ADT as a way to slow down the progression of the cancer.

However, patients whose disease was determined to still be localized within the gland were considered candidates for what is called “salvage” therapy. Salvage treatment is a potentially curative alternative to ADT. Here’s where multiparametric MRI (mpMRI) can play a huge role in detecting localized recurrence. It can reveal the size, shape and location of suspicious lesions, and can show extracapsular extension into the prostate bed or seminal vesicles. (See my article at http://sperlingprostatecenter.com/using-mri-diagnose-localised-prostate-cancer-recurrence-beam-radiation/) Other types of advanced imaging such as PET/CT that utilize isotopes can detect whether the cancer is in the lymph nodes. If imaging can establish that the recurrence is still confined to the gland, an MRI-guided targeted biopsy can diagnose the tumor. Prostatectomy is a difficult salvage treatment with increased risk of side effects, so an image-guided minimally invasive thermal ablation done with extreme heat or cold offers hope of knocking out the cancer. Some patients may be qualified for a focal salvage treatment, and early clinical trials, though small, have shown success while reducing the risk of side effects.

One of the things I love about mpMRI is its ability to save lives, and to preserve quality of life. This means preserving not only the life of the body, but also the life of the mind. Giving recurrent prostate cancer patients an alternative to ADT drugs that can cloud their brains by showing that their disease is still localized is one of the things that makes my work so rewarding.


[i] http://www.webmd.com/prostate-cancer/news/20150512/hormone-therapy-for-prostate-cancer-may-impair-thinking, May 12, 2015.