Endogenous sex hormones and
function in older men
E, Goodman-Gruen D, Patay B
Department of Family and Preventive Medicine,
University of California,
La Jolla 92093-0607, USA.
J Clin Endocrinol Metab 1999 Oct;84(10):3681-5
ABSTRACT The objective
of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design
was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling
men 59-89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected
for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard
neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC)
Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed
recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens
and the "World" Backwards components, and the Trail-Making Test Part B. In age- and education-adjusted analyses, men with
higher levels of total and bioavailable estradiol had poorer scores on the BIMC Test and Mini-Mental State Examination. Men
with higher levels of bioavailable testosterone had better scores on the BIMC Test and the Selective Reminding Test (long-term
storage). Five associations were U-shaped: total testosterone and total and bioavailable estradiol with the BIMC Test; bioavailable
testosterone with the "World" test; and total estradiol with the Trail-Making Test. All associations were relatively weak
but independent of age, education, body mass index, alcohol use, cigarette smoking and depression. In these older men, low
estradiol and high testosterone levels predicted better performance on several tests of cognitive function. Linear and nonlinear
associations were also found, suggesting that an optimal level of sex hormones may exist for some cognitive functions.
gel supplementation for men with refractory depression: a randomized, placebo-controlled trial
Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ,
Am J Psychiatry 2003 Jan;160(1):105-11
supplementation may produce antidepressant effects in men, but until recently it has required cumbersome parenteral administration.
In an 8-week randomized, placebo-controlled trial, the authors administered a testosterone transdermal gel to men aged 30-65
who had refractory depression and low or borderline testosterone levels. METHOD: Of 56 men screened, 24 (42.9%) displayed
morning serum total testosterone levels of 350 ng/dl or less (normal range=270-1070). Of these men, 23 entered the study.
One responded to an initial 1-week single-blind placebo period, and 22 were subsequently randomly assigned: 12 to 1% testosterone
gel, 10 g/day, and 10 to identical-appearing placebo. Each subject continued his existing antidepressant regimen. Ten subjects
receiving testosterone and nine receiving placebo completed the 8-week trial. RESULTS: The groups were closely matched on
baseline demographic and psychiatric measures. Subjects receiving testosterone gel had significantly greater improvement in
scores on the Hamilton Depression Rating Scale than subjects receiving placebo. These changes were noted on both the vegetative
and affective subscales of the Hamilton Depression Rating Scale. A significant difference was also found on the Clinical Global
Impression severity scale but not the Beck Depression Inventory. One subject assigned to testosterone reported increased difficulty
with urination, suggesting an exacerbation of benign prostatic hyperplasia; no other subject reported adverse events apparently
attributable to testosterone. CONCLUSIONS: These preliminary findings suggest that testosterone gel may produce antidepressant
effects in the large and probably underrecognized population of depressed men with low testosterone levels.