Cognition is not modified by large but temporary changes in sex hormones in men.
BACKGROUND
Little is known about the role of testosterone and estradiol on cognition in healthy older men.


OBJECTIVE
The cognitive effects of increasing or lowering testosterone or estradiol were examined.


METHODS
Cognition was assessed before and after 6 wk of double-blind placebo-controlled hormone modification.


METHODS
The study was conducted at an academic medical center.


METHODS
Healthy older (ages 60-80 yr) and younger men (ages 25-35 yr) were recruited from the community.


METHODS
Men were randomized to one of four treatments: 1) maintain testosterone and estradiol at eugonadal levels for young men (GnRH agonist + testosterone gel); 2) block testosterone's conversion to estradiol (GnRH agonist + testosterone gel + aromatase inhibitor); 3) induce hypogonadism (GnRH agonist alone); and 4) all placebo.


METHODS
Measures of executive function, memory, and spatial cognition were obtained before and after treatment. Hormone levels were obtained 10 times over the course of the study.


RESULTS
Counter to expectations, hormone treatment did not affect cognition (P > 0.10). Free testosterone was positively related to spatial cognition in older men after treatment and controlling for age and estradiol level or exclusion of the hypogonadal men (P = 0.02). Estradiol was negatively associated with working memory controlling for the same variables (P = 0.01). Blinding to treatment assignment was maintained, with the exception of the hypogonadal group.


CONCLUSIONS
A significant change in sex hormone status, including complete hypogonadism, does not modify cognition in men. These findings, along with studies that show a risk for neurodegenerative disease in those with low testosterone, suggest that sex hormone status may be important for neuroprotection in aging but not modulation of normal day-to-day cognitive function.
Young
Laura A
LA
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
Neiss
Michelle B
MB
Samuels
Mary H
MH
Roselli
Charles E
CE
Janowsky
Jeri S
JS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000819:agonists / Q000494:pharmacology; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D012739:Gonadal Steroid Hormones; D010919:Placebos; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D016729:Leuprolide