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Diary of hot flashes reported upon occurrence: results of a randomized double-blind study of raloxifene, placebo, and paroxetine

Simon, James A. MD1; Chandler, Julie PhD2; Gottesdiener, Keith MD2; Lazarus, Nicole PharmD2; He, Weili PhD2; Rosenberg, Elizabeth PhD2; Wagner, John A. MD, PhD2; Denker, Andrew E. MD, PhD2

doi: 10.1097/GME.0000000000000218
Original Articles

Objective: This trial examined diaries of hot flash events reported upon occurrence to assess the test/retest reliability of the diaries and their ability to measure treatment effects on hot flash frequency and severity.

Methods: Forty-two postmenopausal women (aged ≥40 y; 5-50 hot flashes/wk) were randomized (3:3:1) to placebo, raloxifene 60 mg, or paroxetine 20 mg daily for 12 weeks. Diaries of hot flash frequency and severity were evaluated at 1-week intervals (twice before study treatment and thrice during study treatment).

Results: Forty-one women were evaluated. Baseline characteristics were similar between groups (eg, mean, 29.8 hot flashes/wk). Concordance correlation coefficients between screening (week −2) and baseline (week −1) measures of hot flash frequency and severity were 0.73 and 0.71, respectively. After 12 weeks, the mean (95% CI) percent changes from baseline in weekly hot flash frequency were as follows: placebo, −37.4% (−60.9 to −14.0); raloxifene, −14.2% (−37.7 to 9.3); paroxetine, −49.8% (−88.6 to −11.0); the mean (95% CI) percent changes in hot flash severity were as follows: placebo, −39.9% (−69.1 to −10.8); raloxifene, −9.6% (−38.8 to 19.6); paroxetine, −36.6% (−84.7 to 11.5). There were no significant differences in hot flash diary results between treatment groups.

Conclusions: Measures of hot flash frequency and severity show acceptable test/retest reliability between screening and baseline. Reductions in vasomotor symptoms by raloxifene are numerically less than those seen with placebo, but no statistically significant treatment differences have been documented in this small study. The large effect of placebo and the significant reduction in vasomotor symptoms by paroxetine are consistent with other studies. The diary seems to be suitable for use in hot flash clinical trials.

From the 1George Washington University and Women’s Health and Research Consultants, Washington, DC; and 2Merck & Co Inc, Whitehouse Station, NJ.

Received September 11, 2013; revised and accepted January 14, 2014.

Funding/support: This study was supported by Merck & Co Inc (Whitehouse Station, NJ).

Financial disclosure/conflicts of interest: J.A.S. has served (within the last year) or is currently serving as a consultant to, or on the advisory boards of, Abbott Laboratories/AbbVie Inc (North Chicago, IL), Agile Therapeutics Inc (Princeton, NJ), Amgen Inc (Thousand Oaks, CA), Apotex Inc (Toronto, Canada), Ascend Therapeutics (Herndon, VA), BioSante (Lincolnshire, IL), Depomed Inc (Menlo Park, CA), Everett Laboratories Inc (West Orange, NJ), Intimina by Lelo Inc (San Jose, CA), Lupin Pharmaceuticals (Baltimore, MD), MD Therapeutics (Boca Raton, FL), Meda Pharmaceuticals Inc (Somerset, NJ), Merck & Co Inc, Noven Pharmaceuticals Inc (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), Novogyne (East Hanover, NJ), Pfizer Inc (New York, NY), Shionogi Inc (Florham Park, NJ), Shippan Point Advisors LLC (Upper Saddle River, NJ), Slate Pharmaceuticals Inc (Durham, NC), Sprout Pharmaceuticals (Raleigh, NC), Teva Pharmaceutical Industries Ltd (Jerusalem, Israel), Warner Chilcott (Rockaway, NJ), and Watson Pharmaceutical Inc (Corona, CA). He has received (within the last year) or is currentlyreceiving grant/research support from Abbott Laboratories/AbbVie Inc, BioSante, EndoCeutics Inc (Quebec, Quebec), Novo Nordisk, Novogyne, Palatin Technologies (Cranbury, NJ), Teva Pharmaceutical Industries Ltd, and Warner Chilcott. He has also served or is currently serving on the speakers bureaus of Amgen Inc, Eisai Inc (Woodcliff Lake, NJ), Merck & Co Inc, Novartis (Basel, Switzerland), Noven Pharmaceuticals Inc, Novo Nordisk, Novogyne, Shionogi Inc, Teva Pharmaceutical Industries Ltd, and Warner Chilcott. J.A.S. was the chief medical officer for Sprout Pharmaceuticals. J.C., K.G., W.H., N.L., E.R., J.A.W., and A.E.D. are current or former employees of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc, and may own stocks or stock options in Merck & Co Inc.

Address correspondence to: James A. Simon, MD, George Washington University, Suite 450, 1850 M Street, NW, Washington, DC 20036. E-mail: jsimon@jamesasimonmd.com

© 2014 by The North American Menopause Society.