Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial

Summary Background The effects of testosterone on cognitive function in older men are incompletely understood. We aimed to establish the effects of long-term testosterone administration on multiple domains of cognitive function in older men with low or low-to-normal testosterone concentrations. Methods We did the randomised, double-blind, placebo-controlled, parallel-group TEAAM trial at three medical centres in Boston, Phoenix, and Los Angeles, USA. Men aged 60 years and older with low or low-to-normal testosterone concentrations (3·47–13·9 nmol/L, or free testosterone 75 years) and study site. The testosterone dose was adjusted to achieve concentrations of 17·3–31·2 nmol/L. Participants and all study personnel were masked to treatment allocation. Multiple domains of cognitive function were assessed as prespecified secondary outcomes by use of standardised tests at baseline and months 6, 18, and 36. We did analyses by intention to treat (in men who had baseline assessments of cognitive function) and per protocol (restricted to participants who completed the study drug and had both baseline and 36 month assessments of cognitive function). The TEAAM trial is registered with ClinicalTrials.gov , number NCT00287586. Findings Between Sept 1, 2004, and Feb 12, 2009, we randomly assigned 308 participants to receive either testosterone (n=156) or placebo (n=152). 280 men had baseline cognitive assessments (n=140 per group). Mean follow-up time was 29·0 months (SD 11·5) in the testosterone group and 31·1 months (9·5) in the placebo group. The last participant completed the study on May 11, 2012. In the testosterone group, mean concentrations of serum total testosterone increased from 10·6 nmol/L (SD 2·2) to 19·7 nmol/L (9·2) and free testosterone concentrations increased from 222 pmol/L (62) to 364 pmol/L (222). In the placebo group, mean concentrations of serum total testosterone were 10·7 nmol/L (SD 2·3) at baseline and 11·1 nmol/L (3·2) post-intervention and free testosterone concentrations were 210 pmol/L (61) and 172 pmol/L (49), respectively. We recorded no between-group differences in changes in visuospatial ability (mean difference: Complex Figure Test −0·51, 95% CI −2·0 to 1·0), phonemic or category verbal fluency (phonemic fluency test 0·90, −