MSI-FLASH: An RCT of Yoga and Ultra Low-Dose Estrogen Gel for Vasomotor Symptoms

Susan D Reed, MD, MPH

This application describes one of five proposals, being submitted in conjunction with the network application entitled, "The Menopausal Symptoms Initiative -Finding Lasting Answers to Sweats and Hot Flashes (MSI-FLASH)". Our network and data coordinating center (DCC) will be jointly led by two Co-Principal Investigators of the Women's Health Initiative, Clinical Coordinating Center (Seattle) who have worked together for over a decade (LaCroix, Anderson, PIs). The MSI-FLASH network has five clinical sites located in Boston, MA (Cohen, Joffe, PIs), Indianapolis, IN (Carpenter, PI), Oakland, CA (Sternfeld, Caan, PIs), Philadelphia, PA (Freeman, PI) and Seattle, WA (Newton, Reed, PIs).

This multidisciplinary investigator group proposes five randomized controlled trials testing a range of behavioral, mind-body, hormonal and pharmacologic interventions. Our aim is to fulfill the main objective of the RFA, "New Interventions for Menopausal Symptoms (U01)," to accelerate the identification of effective remedies for vasomotor symptoms (VMS). In this site application we propose a multicenter RCT of yoga and ultra low-dose estradiol (E2) gel and placebo gel to be conducted in Seattle, Indianapolis and Boston.

The primary aims of this RCT are to evaluate the effects of yoga alone and ultra-low dose E2 gel alone vs placebo gel on: 1) subjective VMS frequency; and 2) VMS bothersomeness. Secondary aims: 1) To evaluate the effects of yoga alone and ultra-low dose E2 gel alone on objective VMS frequency, sleep and mood; and 2) To examine whether the combined effect of yoga and ultra low-dose E2 is greater than the effect of either alone on the above outcomes (this aim will only be explored if yoga alone affects at least one of these outcomes).

Hypotheses: 1) Yoga will improve subjective VMS more than placebo gel; 2) Yoga will improve VMS bothersomeness more than placebo gel; 3) Ultra low-dose E2 gel will improve subjective VMS more than placebo gel; and 4) Ultra low-dose E2 gel will improve symptom bothersomeness more than placebo gel.

To accomplish our specific aims we will: 1) recruit and randomize 400 women to one of 4 treatment arms for 12 weeks (placebo gel; yoga + placebo gel; ultra low-dose E2 gel; yoga plus ultra low-dose E2 gel); 2) measure above outcomes at baseline and 12 weeks; and 3) compare changes in outcomes in yoga and ultra low-dose E2 gel groups to placebo gel.

Funding Source: Fred Hutchinson Cancer Research Center
Contact: Susan D Reed, MD, MPH
Ends 8/31/2013

EQUOL and Vasomotor Symptoms

Susan D Reed, MD, MPH

Soy foods contain two isoflavones, genestein and daidzein, that act as either estrogen agonists or estrogen antagonists, depending on the estrogen receptor location. Several intervention studies have evaluated the effects of soy isoflavones on menopausal symptoms, particularly vasomotor symptoms. However, these studies have yielded inconsistent results.

Daidzein is metabolized in the lower segment of the digestive system by intestinal flora, to yield equol (an active metabolite). Equol's physiological activity has been receiving close attention, since the potential to bind to estrogen receptors (ERs), particularly ER-beta, is higher with equol than with soy isoflavone itself. Equol formed by intestinal flora is absorbed and eliminated into urine. Findings of another recent study suggest that menopausal symptoms are associated more closely with equol than with daidzein or genistein ingested directly from foods. Furthermore, in this same study, the percentage of women capable of eliminating equol into urine was low for women with more severe menopausal symptoms, suggesting that the presence/absence of equol formation in the intestine is closely related to the severity of menopausal symptoms.

We are specifically interested in the interplay between ingestion of soy foods, equol producer status, and vasomotor symptoms in midlife women. In the wake of the Women's Health Initiaitive, use of hormone therapy for vasomotor symptoms decreased dramatically, and women are seeking safe alternatives for symptom management. The proposed study is a first step in evaluating the interplay between soy food metabolism and relief of VMS, with the ultimate goal of determining whether more specific treatment with equol may relieve VMS in subsets of women.

Our specific aims are:

  1. To investigate the prevalence of soy food consumption and associated prevalence of vasomotor symptoms in healthy midlife US women in the Seattle area not using hormone therapy
  2. Among a subset of women identified with adequate soy intake, evaluate urinary isoflavonoid excretion and relation to objective and subjective frequency of vasomotor symptoms and subjective severity and bother

Funding Source: Group Health Center for Health Studies
Contact: Susan D Reed, MD, MPH
Ends 2/28/2011