The Effects of Combined Androgen Blockade on Cognitive Function

Men with prostate specific antigen (PSA) only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years.

These patients are often treated with androgen suppression. Some men on hormonal therapy report feelings and sensations comparable in some ways to those of women undergoing surgical menopause.

The "hot flashes" and loss of libido and erectile function that often accompany androgen blockade for men are well known, but what about subtler effects?

Researchers at University of Washington School of Medicine in Seattle decided to look at the effects of androgen suppression on cognitive function.

A group of hormone naïve patients without evidence of metastases with an increasing PSA were treated with intermittent androgen suppression consisting of 9 months of leuprolide and flutamide followed by an off treatment period determined by the increase in PSA. Cognitive function tests were administered at baseline, after 9 months of androgen suppression and after 3 months off treatment. Cognitive tests measured spatial abilities, spatial memory, verbal fluency, verbal memory and selective attention. A total of 19 patients 52 to 76 years old completed the intermittent androgen suppression study along with 15 healthy community dwelling control participants.

Results: Combined androgen blockade reduced PSA and testosterone in all patients compared to baseline. Patients did not significantly change on measures of verbal and spatial memory, executive functions or language. Patients declined on a measure of spatial rotation and improved on a measure of verbal memory during treatment which continued during the off treatment period.

Conclusions: Although preliminary, these findings demonstrate that 9 months of combined androgen blockade resulted in a beneficial effect on verbal memory but adversely affected a measure of spatial ability. Intermittent androgen suppression for a period of 9 months in otherwise healthy men with prostate cancer may have beneficial and adverse effects on cognition that are selective.

Prostate cancer is the most common form of noncutaneous cancer diagnosed in American men.

Androgen deprivation is the most common treatment for approximately 22% of patients in whom primary therapy fails.

Intermittent androgen suppression (IAS) is a treatment strategy that cycles androgen withdrawal (6 to 9 months) with an off treatment period allowing the testosterone levels to return to physiological levels. Treatment is then reinstated as the prostate specific antigen (PSA) reaches a threshold dependent on primary therapy. The benefits of intermittent versus continuous androgen suppression have not yet been proven in phase III randomized clinical trials, although animal data suggest that intermittent exposure to androgens may prolong the interval to androgen independence.

Phase II studies have demonstrated that IAS improves quality of life during the off treatment period and may reduce long-term toxicities related to testosterone deficiency. Long-term physiological consequences of androgen suppression include obesity, anemia, loss of bone mineral density, muscle atrophy, gynecomastia and possibly mood changes. We and others have previously shown a significant loss in bone mineral density due to androgen suppression, which has been observed as early as 9 months.

To our knowledge the effects of combined androgen blockade on cognition and mood have not been previously described in this patient population. Anecdotally, patients have reported alterations in cognition and memory. In healthy older men decreases in endogenous testosterone levels correlate with declines in memory, and androgen therapy has been shown to improve spatial memory.

We determine the impact of intermittent androgen suppression on cognitive function in patients with prostate cancer in biochemical relapse without evidence of metastases. We hypothesized that combined androgen blockade would alter and possibly impair memory and cognitive function.

The Journal of Urology: Volume 170(5) November 2003 pp 1808-1811 The Effects of Combined Androgen Blockade on Cognitive Function During the First Cycle of Intermittent Androgen Suppression in Patients With Prostate Cancer

CHERRIER, M. M.; ROSE, A. L.; HIGANO, C. From the Departments of Psychiatry and Behavioral Sciences (MMC) and Medicine (ALR, CH), University of Washington School of Medicine, Seattle, Washington

The study was paid for by TAP Pharmaceuticals, maker of Lupron (leuprolide), a leading androgen suppression drug, and Integrated Therapeutics, the health management unit of Schering-Plough, manufacturer of the anti-androgen drug Eulexin (flutamide).

Investigator Dr. Celeste Higano declared financial interest and/or other relationship with Cell Therapeutics Inc., Myriad Pharm, Atrix Lab, Takeda Pharmaceuticals, Novartis, Dendreon, TAP Pharmaceuticals, Lilly, Cell Genesys, Abbott, NW Biotherapeutics and Abgenix.

Update: Hormone therapy for prostate cancer affects men's mental function, March 2005

experience of cancer: a qualitative study BMJ March 2004

I think that the worst thing about getting a diagnosis like this is a feeling of isolation, because you feel that your world has suddenly shrunk and all you can think about is yourself and you feel very frustrated because nobody has maybe experienced this. And when you're able to talk to other patients it's just very good to know that other people have been through this and to kind of share the experience with other people, and you feel much less isolated... It's not just the medical information aspect, it's just a kind of support, moral support, which is very, very important when you've had a diagnosis of cancer." (51 year old man with prostate cancer)

Prostate Cancer Treatment Guidelines for Patients Version III, October 2002 The national Comprehensive Cancer Network

Prostate Nomogram: an online tool to help physicians and patients predict the outcomes of treatment options. At MSKCC website.

Cáncer de la próstata Guías de la
NCCN para el tratamiento de
los pacientes Transferencia directa aquí 1-800-ACS-2435
1-888-909-NCCN