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.
The goal of this phase II clinical trial was to evaluate the effects of red clover, black cohosh, and combined hormone therapy on cognitive function and objective hot flashes in comparison with placebo in women with moderate to severe vasomotor symptoms. Results indicate that neither botanical supplement had an effect on cognitive function and that combined hormone therapy reduces objective hot flashes but worsens some aspects of verbal memory.
From the Departments of 1Psychiatry and 2Psychology, University of Illinois at Chicago, Chicago, IL; 3Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL; and 4Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL.
Received February 17, 2009; revised and accepted April 2, 2009.
Funding/support: This research was supported by grants K01AT002321-01 and R21AT001868-01 from the National Institutes of Health (NIH)/National Center of Complementary and Alternative Medicine (NCCAM). The NIH/NCCAM Botanical Dietary Supplements for Women's Health (P50 AT000155 NIH/NCCAM Botanical Dietary Supplements for Women's Health; Norman Farnsworth, principal investigator) provided pilot funds for this neurocognitive study and funded the parent study.
Financial disclosure/conflicts of interest: Dr. Maki has received grant support from the Soy Health Research Board and Wyeth Ayerst. Dr. Maki has also received honorarium from the Soy Health Research Foundation, Wyeth Pharmaceuticals, Fanizzi Associates and Genaera Corporation.
Address correspondence to: Pauline M. Maki, PhD, Department of Psychiatry (MC 913), University of Illinois at Chicago, Chicago, IL 60612. E-mail: email@example.com