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Timing and persistence of effect of conjugated estrogens/bazedoxifene in postmenopausal women

Kagan, Risa MD, FACOG, CCD, NCMP; Komm, Barry S. PhD; Ryan, Kelly A. MS, BSN; Lavenberg, Joanne BS; Yu, Ching-Ray PhD; Pinkerton, JoAnn V. MD

doi: 10.1097/GME.0000000000000688
Original Articles
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Objective: The aim of the study was to determine the time course of effect with conjugated estrogens/bazedoxifene (CE/BZA) in nonhysterectomized postmenopausal women in five phase 3 trials.

Methods: This post hoc analysis identified when CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg first achieved a statistically significant difference (P < 0.05) versus placebo in individual trials and the duration the difference persisted for prespecified efficacy endpoints.

Results: CE/BZA significantly reduced hot flush frequency beginning at weeks 2 to 4 and severity at weeks 3 to 6; benefits were maintained through month 24. Significant improvements in lumbar spine, total hip, femoral neck, and femoral trochanter bone mineral density were evident at month 6 or 12 and changes in bone turnover markers at month 3 or 6; benefits were maintained throughout the studies (12 or 24 mo). In symptomatic women with less than 5% vaginal superficial cells at baseline, vaginal maturation index was significantly improved by week 4. Reductions in parabasal cells were maintained throughout the studies (through months 3 and 24), but superficial cell count changes persisted only with the higher CE/BZA dose. Menopause-Specific Quality of Life total and vasomotor domain scores were improved at all assessments, from months 3 through 24. Some measures of sleep, especially quality and time to fall asleep, improved during weeks 4 to 8 and were maintained in a majority of weeks thereafter.

Conclusions: In the context of studies designed primarily to evaluate efficacy at final study endpoints, both doses of CE/BZA achieved significance versus placebo at early assessments for most outcomes, and benefits were well maintained.

1University of California, San Francisco and East Bay Physicians Medical Group, Berkeley, CA

2Pfizer Inc, Collegeville, PA

3Pfizer Inc, New York, NY

4University of Virginia Health System, Charlottesville, VA.

Address correspondence to: Risa Kagan, MD, FACOG, CCD, NCMP, Clinical Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF, East Bay Physicians Medical Group, Affiliated with Sutter East Bay Medical Foundation, 2500 Milvia Street, Berkeley, CA 94704. E-mail: kaganr@sutterhealth.org

Received 10 December, 2015

Revised 5 April, 2016

Accepted 5 April, 2016

This analysis was presented at The North American Menopause Society, October 15-18, 2014, National Harbor, MD.

Funding/support: This study was sponsored by Pfizer Inc. Medical writing support was provided by Lauren Cerruto of Peloton Advantage and was funded by Pfizer Inc.

Financial disclosure/conflicts of interest: R.K. has served as a consultant/advisory board member for Amgen, Foundation for Osteoporosis Research and Education/American Bone Health, Merck & Co, Noven Pharmaceuticals, Novo Nordisk A/S, Own the Bone Advisory Board of the American Orthopedic Association, Pfizer, Shionogi, and Sprout Pharma; has received grants/research support (fees to Alta Bates Summit Medical Center, Jordan Research and Education Institute) from TherapeuticsMD; has served on a speaker's bureau for Novo Nordisk A/S, Shionogi, Noven Pharmaceuticals, and Pfizer; and has received editorial writing support from Pfizer and Shionogi. J.V.P. (all fees to University of Virginia) has served as a consultant for Pfizer; has received grants/research support from TherapeuticsMD; has received travel funds for consulting from Pfizer; and has received editorial writing support from Pfizer, TherapeuticsMD, Shionogi, and Noven Pharmaceuticals. B.S.K., J.L., K.A.R., and C.-R.Y. are employees of Pfizer.

© 2016 by The North American Menopause Society.