Effects of testosterone and estrogen replacement on memory function

Testosterone insufficiency has been associated with psychosexual problems, reduced psychological well-being, and negative metabolic consequences, whereas less is known about the effects on cognition. The aim of this study was to investigate the effect of adding testosterone to estrogen therapy on memory functions in oophorectomized women.

In a randomized, double-blind, placebo-controlled design, women with surgically induced menopause (n = 50; mean [SD] age, 54.0 [2.9] y) received estradiol valerate in combination with testosterone undecanoate or placebo. The women were assessed with a self-report questionnaire regarding memory and neuropsychological tests for verbal and spatial episodic memory and incidental learning at baseline, at the time of crossover, and after completion of treatment.

Testosterone undecanoate 40 mg added to estrogen therapy had a negative effect on immediate but not delayed verbal memory at 24 weeks. Subjective and objective memory showed some correspondence as the women in the estrogen + placebo treatment group rated decreased everyday memory problems at 24 weeks compared with baseline. This was not observed in the women in the estrogen + testosterone treatment. Verbal attention span deteriorated from baseline with estrogen + placebo treatment but not with the estrogen + testosterone treatment. However, there was no significant treatment effect between the two groups.

Adding testosterone to estrogen treatment deteriorated immediate verbal memory compared with estrogen + placebo, while other memory functions were unaffected.