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Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial

Crawford, Sybil L. PhD1; Jackson, Elizabeth A. MD2; Churchill, Linda MS1; Lampe, Johanna W. PhD3; Leung, Katherine MPH1; Ockene, Judith K. PhD1

Menopause: The Journal of The North American Menopause Society: September 2013 - Volume 20 - Issue 9 - p 911–921
doi: 10.1097/GME.0b013e3182829413
Original Articles

Objective The relatively modest benefit of vasomotor symptom relief in clinical trials of isoflavones may reflect once-daily dosing and low percentages of participants who are able to metabolize daidzein into equol, a potentially more biologically active isoflavone. This pilot study examined whether symptom reduction was greater with more frequent administration and with higher daily doses. In addition, we explored possible effect modification by equol producer status.

Methods We randomized 130 perimenopausal (no menses in the past 3 mo) and postmenopausal (≥12 mo of amenorrhea) women with a mean of five or more moderate/severe hot flashes per day to treatment arms with varying total daily isoflavone doses and dosing frequency, separately for equol producers and nonproducers. Participants recorded the daily frequency and severity of hot flashes. Analyses compared mean daily hot flash intensity scores (sum of hot flashes weighted by severity) by total daily dose and by dosing frequency. Dose- and frequency-related differences were also compared for equol producers and nonproducers.

Results Hot flash intensity scores were lowest in women randomized to the highest total daily dose (100-200 mg) and in women randomized to the highest dosing frequency (twice daily to thrice daily), with greater benefits on nighttime scores than on daytime scores. Dose- and frequency-related differences were somewhat larger in equol producers than in nonproducers.

Conclusions These results suggest that a twice-daily to thrice-daily dosing frequency may improve the benefit of isoflavones for vasomotor symptom relief, particularly in equol producers and for nighttime symptoms. Larger studies are needed to confirm these findings.

From the 1Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA; 2Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; and 3Cancer Prevention Program, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.

Received October 18, 2012; revised and accepted December 11, 2012.

Funding/support: This study was supported by the National Center for Complementary and Alternative Medicine (grant AT002522).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Sybil L. Crawford, PhD, University of Massachusetts Medical School, Room 228, Shaw Building, 55 Lake Avenue North, Worcester, MA 01655. E-mail:

© 2013 by The North American Menopause Society.