PSA Rising. March 1, 2005 -- Drugs that block testosterone and other sex hormones are widely used in treatments for men with prostate cancer. Androgens (male hormones) enable receptors on prostate cancer cells to stimulate tumor growth. Hormonal blockade therapy to shut down testosterone production can shrink prostate cancer tumors and halt pain, and may extend life.
But for men who take these drugs side effects can be profound. Loss of sexual desire, impotence, penile shrinkage, loss of muscle, hot flashes, anemia and fragile bones (osteoporosis) are documented side effects of androgen blockade, though not always discussed between doctor and patient.
Now researchers are documenting subtle ways in which hormonal blockade affects male brain function. In doing so they are looking not just at loss of testosterone but also at loss of estradiol.
Loss of testosterone can lower estradiol, usually considered a female hormone but found also in men. Testosterone and estradiol are important in neurological development and play a particularly important role in the cognitive areas of learning and memory. Previous studies in women have shown that declining estradiol levels affect cognition but until now little data existed in men.
Now in two related studies Eeva Salminen, M.D. and colleagues at Turku University Hospital, Finland have documented how testosterone deprivation and estradiol deprivation affect the mental functioning of men treated with hormone therapy for prostate cancer. Most though not all of the effects are negative.
Older prostate cancer patients (mean age 65 years) who were tested with the drugs showed "significant associations between cognitive performances and testosterone decline," Salminen reported in November, 2004. Now in a second study slated to appear in April 2005, the same team says that low estradiol levels affect patients' visual and numerical processing.
Testosterone deprivation affected men's attention and working memory and speed of messages from eye to brain and back to hand or other body part ("visuomotor slowing"). Patients undergoing therapy showed "impaired hit rate in a vigilance test, impaired delayed recall and recognition speed of letters, but improvement in object recall." These results suggest "selective associations between testosterone decline and cognition."
Changes in cognitive performance with loss of normal serum testosterone levels have "substantial implications for informed patient support in prostate cancer," the researchers state.
In a follow up study, Dr. Salminen documented cognitive dysfunction in these men which appeared to be related to a decline in serum estradiol brought on by hormonal treatment.
In both of the studies, patients were tested at baseline and at 6 and 12 months on androgen deprivation (AD). Cognitive performances were evaluated with standardized measures of information processing, including working memory and attention, visual and verbal skills, and memory performances in 31 tests.
Mental abilities found to be significantly associated with decline in estradiol included "visual memory of figures " (i.e. shapes) and "recognition speed of numbers." These abilities were impaired at 6 months after starting drugs. Verbal fluency, however, appeared improved at 12 months. Other cognitive domains appeared unaffected by estradiol decline. The character of change (impairment or improvement) depended on the magnitude of estradiol decline.
Surprisingly, the researchers conclude that despite these "selective and marginal" changes associated with estradiol declines, "cognitive function appears to be well preserved during 12 months AD in men without previous neurological or psychological diseases."
Androgen-deprivation therapy (AD) in the form of injectable "depot" drugs such as Lupron (leuprolide) and Zoladex (goserelin) is one of the most widely used treatments for prostate cancer. Since the 1980s, these injectible "chemical castration" drugs have been used as first-line therapy for advanced prostate cancer. In addition, some physicians prescribe hormone blockade before and/or after surgery or radiotherapy for men with high-risk earlier stage prostate cancer.
The Finnish researchers conclude that adverse effects of hormonal manipulation to treat prostate cancer "need to be established in view of its increasing use as an adjuvant treatment." Objective confirmation of diminished mental sharpness may come as a blow, but men themselves describe hormonal blockade as a "lead suit" and this new information may help doctors and patients discuss the problem more freely and select better therapies.
Links
Article: "Estradiol and Cognition during Androgen Deprivation in Men with Prostate Carcinoma," , R.I. Portin, A. Koskinen, H. Helenius, and M. Nurmi, CANCER; Published Online: February 28, 2005 (DOI: 10.1002/cncr.20962); Print Issue Date: April 1, 2005.
A previous study in the USA: Effects of Combined Androgen Blockade on Cognitive Function, 2003
Edited by J. Strax, March 1, 2005
