Effects of botanicals and combined hormone therapy on cognition in postmenopausal women

Objective: The aim of this study was to characterize the effects of red clover, black cohosh, and combined hormone therapy on cognitive function in comparison to placebo in women with moderate to severe vasomotor symptoms. Methods: In a phase II randomized, double-blind, placebo-controlled study, 66 midlife women (of 89 from a parent study; mean age, 53 y) with 35 or more weekly hot flashes were randomized to receive red clover (120 mg), black cohosh (128 mg), 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/ MPA), or placebo. Participants completed measures of verbal memory (primary outcome) and other cognitive measures (secondary outcomes) before and during the 12th treatment month. A subset of 19 women completed objective, physiological measures of hot flashes using ambulatory skin conductance monitors. Results: Neither of the botanical treatments had an impact on any cognitive measure. Compared with placebo, CEE/MPA led to a greater decline in verbal learning (one of five verbal memory measures). This effect just missed statistical significance (P = 0.057) in unadjusted analyses but reached significance (P = 0.02) after adjusting for vasomotor symptoms. Neither of the botanical treatment groups showed a change in verbal memory that differed from the placebo group (Ps > 0.28), even after controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led to a decrease in immediate digit recall and an improvement in letter fluency. Only CEE/MPA significantly reduced objective hot flashes. Conclusions: Results indicate that a red clover (phytoestrogen) supplement or black cohosh has no effects on cognitive function. CEE/MPA reduces objective hot flashes but worsens some aspects of verbal memory.