This application proposes a clinical trial within a network of scientists who are highly knowledgeable about the menopausal transition and experienced in the conduct of women's health trials in order to fulfill the main objective of this RFA, which is to accelerate the identification of effective remedies to relieve vasomotor symptoms. This application is submitted in conjunction with the network titled "The Menopausal Symptoms Initiative - Finding Lasting Answers to Sweats and Hot Flashes" (MSI-FLASH). The Data Coordinating Center (DCC) of the network is led by A. LaCroix and G. Anderson, who have served as Co-Principal Investigators of the Women's Health, Initiative, Clinical Coordinating Center (Seattle) for more than a decade. The MSI-FLASH network has 5 clinical field sites located in Boston (L. Cohen and H. Jaffe, PIs), Indianapolis (J Carpenter, PI),Oakland, CA (B Sternfeld and B Caan, PIs),Philadelphia (E. Freeman, PI) and Seattle (K Newton and S Reed, PIs). This multi disciplinary investigator group proposes 5 randomized controlled trials that test a range of behavioral, mind-body, hormonal and pharmacologic interventions for menopausal hot flashes. This field site proposes a randomized, placebo-controlled trial to determine the efficacy of a serotonergic reuptake inhibitor (SSRI) for reducing hot flashes associated with menopause and determine the effects of known covariates of hot flashes in treatment response.
The specific aims are to 1) Determine the efficacy of the SSRI escitalopram compared with placebo in reducing the frequency, severity and bothersomeness of hot flashes;2) Determine associations of baseline measures of anxiety, depressed mood, poor sleep, perceived stress, menopausal stage and race with improvement of hot flashes;3) Determine whether changes in anxiety and depressed mood during treatment are associated with decreases in hot flashes with escitalopram compared to placebo;4) Determine the time course for improvement of hot flashes with escitalopram compared to placebo. Approximately 180 women will be randomized to double-blind treatment, and enrollment will be stratified to obtain equal numbers of African American and white women. It is expected that 3 other field sites of the Network will also conduct this protocol, providing a collaborative and multi disciplinary approach, diverse populations and a rapid completion of the treatment protocol. Increased information about treatment efficacy and the factors associated with treatment response, including whether there are racial differences in response to treatment, will lead to better therapeutic strategies for women who experience distressing and disruptive menopausal symptoms. Information about responses to a serotonergic treatment may increase understanding of associations between hot flashes and the serotonergic system.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAG1-ZIJ-5 (M2))
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Hannah, Judy S
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University of Pennsylvania
Obstetrics & Gynecology
Schools of Medicine
United States
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Diem, Susan J; Joffe, Hadine; Larson, Joseph C et al. (2014) Effects of escitalopram on markers of bone turnover: a randomized clinical trial. J Clin Endocrinol Metab 99:E1732-7
Joffe, Hadine; Guthrie, Katherine A; LaCroix, Andrea Z et al. (2014) Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial. JAMA Intern Med 174:1058-66
Newton, Katherine M; Carpenter, Janet S; Guthrie, Katherine A et al. (2014) Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network. Menopause 21:45-58
Reed, Susan D; Mitchell, Caroline M; Joffe, Hadine et al. (2014) Sexual function in women on estradiol or venlafaxine for hot flushes: a randomized controlled trial. Obstet Gynecol 124:233-41
Newton, Katherine M; Reed, Susan D; Guthrie, Katherine A et al. (2014) Efficacy of yoga for vasomotor symptoms: a randomized controlled trial. Menopause 21:339-46
Reed, Susan D; Guthrie, Katherine A; Newton, Katherine M et al. (2014) Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements. Am J Obstet Gynecol 210:244.e1-11
Sternfeld, Barbara; LaCroix, Andrea; Caan, Bette J et al. (2013) Design and methods of a multi-site, multi-behavioral treatment trial for menopausal symptoms: the MsFLASH experience. Contemp Clin Trials 35:25-34
Carpenter, Janet S; Guthrie, Katherine A; Larson, Joseph C et al. (2012) Effect of escitalopram on hot flash interference: a randomized, controlled trial. Fertil Steril 97:1399-404.e1
Reed, Susan D; Guthrie, Katherine A; Joffe, Hadine et al. (2012) Sexual function in nondepressed women using escitalopram for vasomotor symptoms: a randomized controlled trial. Obstet Gynecol 119:527-38
Freeman, Ellen W; Guthrie, Katherine A; Caan, Bette et al. (2011) Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA 305:267-74