15 December 2005. For years, postmenopausal women have agonized over the risks and benefits of estrogen replacement therapy. Now comes a hint that elderly men, particularly those with Alzheimer disease (AD), might benefit from a testosterone top up. A study reported in yesterday’s Archives of Neurology online concludes that the male hormone, applied daily as a cream, can lead to improved quality of life in men with mild to moderate forms of the disease.
The pilot study was led by Jeffrey Cummings and colleagues at the University of California Los Angeles, and also at Irvine and San Francisco. At total of 38 elderly men (22 healthy controls and 16 with AD) received the daily testosterone balm, or a placebo, for 24 weeks, during which first author Po Lu and colleagues gathered quality-of-life data. Then, at the end of the study, the researchers tested participants for serum hormones, cognitive ability, and neuropsychiatric symptoms.
Lu and colleagues reported that caregivers found AD patients did better when given the hormone. Assessments revealed a small, though statistically significant, increase in quality of life at week 24 of the trial compared to week 12. Unfortunately, the patients did not seem to notice this improvement because self-assessment scores were no different between subjects in the hormone and placebo groups. Likewise, doctors failed to detect any benefit for the patient, as judged by a test called the Clinician’s Interview-Based Impression of Change. It is unclear why only caregivers noticed the change, but the trial was double-blinded to ensure that they did not know which patients were receiving the hormone. In healthy men, self-assessments did indicate that the topical testosterone increased quality of life; however, this trend was not statistically significant.
Cognitive and neuropsychiatric outcomes were disappointing. Though serum testosterone and dihydrotestosterone increased markedly in the treatment groups, subjects taking the hormone cream performed no better in cognitive tasks than did those on placebo. This finding should be considered in the context of results from another recent study led by Suzanne Craft and colleagues at the University of Washington, Seattle. That small pilot trial suggested that the hormone can improve spatial memory in men with mild cognitive impairment or AD (see Cherrier et al., 2005).
Cummings and colleagues also failed to find any neuropsychiatric improvement in AD patients on testosterone. But the steroid did seem to maintain (or slightly improve) visual motor skills—patients on placebo scored poorer in such tasks at the end of the trial. This result suggests that testosterone may protect against loss of visual-spatial function (see also the recent report by Tan et al., 2003).
The authors caution that the present results are preliminary and do not warrant routine treatment of AD and healthy control men with testosterone. Future studies with larger sample sizes will be needed, they stress. In this regard, it is worth noting the “on again, off again” recommendations about estrogen replacement therapy for women. These accompanied each new estrogen replacement trial, starting in the 1970s and culminating when the estrogen-only arm of the Women’s Health Initiative trial was prematurely halted because of safety concerns (see related National Institutes of Health information). Public concern over safety was an issue in this testosterone trial, as well. Lu and colleagues report that “subject recruitment was more difficult than anticipated due to the strict inclusion and exclusion criteria and the caregivers’ fear of adverse events associated with testosterone.” Researchers who wish to recruit large numbers of AD patients for testosterone trials may have some heavy lifting to do.—Tom Fagan.
Lu PH, Masterman DA, Mulnard R, Cotman C, Miller B, Yaffe K, Reback E, Porter V, Swerdloff R, Cummings JL. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol online. December 14, 2005. Abstract