Testosterone for Alzheimer's?

Summarized by Robert W. Griffith, MD
March 13, 2006

Introduction

In 2004 there was a report that men with low testosterone levels are at an increased risk of developing Alzheimer's disease (see the first link below). A natural question is whether testosterone supplements could be given to such men in with the aim of preventing Alzheimer's. (This would be analogous to the attempts to prevent or delay progress of the disease in women using an estrogen/progestagen preparation or estrogen alone.) Before these preventative trials have been reported, a publication of the effect of using the hormone in treating men with mild dementia has appeared in the journal Archives of Neurology .Earlier pilot trials have provided some tantalizing results. Here's a summary of the findings in this latest study.

What was done

This was a 24-week, randomized, double-blind, placebo-controlled, parallel-group study¹. Men with Alzheimer's disease were recruited from University of California clinics, and healthy men to act as controls were found through newspaper advertisements. There were 16 patients and 22 healthy controls; after randomization, 9 patients and 14 healthy controls received testosterone, while 9 patients and15 controls received the placebo.

The medications used were an alcoholic gel preparation containing 75 mg testosterone and a gel containing no active ingredients, applied to the skin at three different sites once a day.

A battery of tests of mental function, neuropsychiatry symptoms, overall functioning, and quality-of-life scales were done at baseline and after 24 weeks; some tests were done at weeks 4 and 12 into the study, as well. The quality-of-life scale obtained separate ratings from the patient and from his caregiver. Serum testosterone and other hormone assays were done at baseline and after 24 weeks' treatment.

What was found

The Alzheimer patients were 70 and the healthy controls were 62 years old, on average. In general, the Alzheimer patients had slightly lower levels of serum testosterone (total, free, and dihydrotestosterone) and higher levels of female hormones (follicle stimulating and luteinizing hormones) at baseline than the healthy controls.

As expected, Alzheimer patients experienced larger increases in serum testosterone (all types) and decreases in follicle stimulating and luteinizing hormones during the study, compared with the healthy controls. No significant effects of testosterone treatment were seen on the tests of mental functioning, but there was a non-significant improvement in measures of so-called visuospatial function (the sort of skill required to do a jigsaw puzzle) in the Alzheimer patients given testosterone.

There was a significantly greater improvement in the caregivers' scores of the quality-of-life for the patients treated with testosterone, compared with those given the placebo gel. In the healthy controls, the self-rated quality-of-life scores remained at baseline levels in those given testosterone, while those given the placebo developed reduced scores over the course of the study.

There were no significant side effects in any of the participants; one Alzheimer patient complained of a rash at the gel application site.

What these findings mean

This study showed that testosterone gel given to Alzheimer patients produced a trend to improved quality-of-life over a 6-month period while placebo-treated patients had a significant decline. Healthy men (about 8 years younger) had similar changes, but they were smaller and not statistically significant.

This particular benefit of testosterone has not been reported before. However, the slight improvement seen in patients with regard to visuospatial function is in line with prior studies; the individual results showed a parallel between improvements in test scores and changes in serum testosterone level.

This was a small study - not very many patients. The full dose of testosterone may not have been absorbed from the gel. And the tests used to detect changes in the disease may not have been well-chosen. Nevertheless, positive results of any kind are clearly a spur to further exploration of the use of hormone replacement treatment in Alzheimer's. Maybe they can act as a further stimulus to start prevention studies, which would have to be done on a very large scale. In the meantime, anything that improves the quality-of-life of Alzheimer patients (or even the perceived quality-of-life) is worth considering for use in individual cases.

Source

• Effects of testosterone on cognition and mood in male patients with mild Alzheimer's disease and healthy elderly men. PH. Lu, DA. Masterman, R. Mulnard,  et al., Arch Neurol, 2006, vol. 63, pp. 177--185

Footnotes
1. Randomized means subjects are assigned to receive the test drug or an inactive substance (placebo) at random. Double-blind means neither the subjects nor the treating doctors know which group the subject belongs to - active or placebo. In a placebo-controlled trial, results with the test drug are compared to those with an inactive substance; other controlled studies may compare the test drug with a known effective treatment. Parallel-group means the test drug and placebo groups are studied during the same period; another type of study is a cross-over trial, in which some of the subjects are given first the test drug and then the placebo, while others get the both treatments but in the reverse order.

Related Links
Alzheimer's Related to Low Testosterone Levels?
Low Testosterone Levels Linked to Atherosclerosis
HRT for Men Is Risky, Too

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