A randomized trial of the effect of testosterone and estrogen on verbal fluency, verbal memory, and spatial ability in healthy postmenopausal women

Objective

To test the causal relationship between sex hormones and cognitive skills in postmenopausal women. We hypothesized that testosterone would decrease verbal memory and verbal fluency and increase spatial ability compared with a placebo. For estrogen, we conversely hypothesized that the treatment would increase verbal fluency and verbal memory and decrease spatial ability.

Design

Randomized, double-blind, placebo-controlled, parallel-group trial.

Setting

Women's health clinical research unit at a university hospital.

Patient(s)

Two-hundred healthy, naturally postmenopausal women aged 50–65 years.

Intervention(s)

Randomization to 4 weeks' treatment with testosterone (testosterone undecanoate, 40 mg/day), estrogen (oral E₂ 2 mg/day) or placebo.

Main Outcome Measure(s)

Comparisons in verbal fluency, verbal memory, and spatial ability between the three treatment groups.

Result(s)

We found no significant effects of testosterone or estrogen on verbal fluency, verbal memory, or spatial ability.

Conclusion(s)

Our results give no support for short-term testosterone or estrogen treatment having any substantial effect on verbal fluency, verbal memory, or spatial ability in healthy postmenopausal women.

Key Words: Estrogen, testosterone, memory, spatial ability, cognition, randomized trial