Objective: This study aims to investigate the efficacy and safety of daily drospirenone/17β-estradiol in two low-dose combinations (0.25 mg/0.5 mg and 0.5 mg/0.5 mg, respectively) versus 17β-estradiol (0.3 mg) or placebo in postmenopausal women with moderate to severe vasomotor symptoms.
Methods: Seven hundred thirty-five postmenopausal women aged 40 years or older who experienced a minimum of 7 to 8 moderate to severe hot flushes per day, or 50 to 60 moderate to severe hot flushes per week, participated in a 12-week, double-blind, randomized, placebo-controlled study. The primary efficacy variables were mean changes from baseline to weeks 4 and 12 in the weekly frequency and weekly mean daily severity of moderate to severe hot flushes recorded daily by the participants on diary cards.
Results: All active treatments were significantly more effective than placebo for the primary efficacy variables for drospirenone/17β-estradiol (P < 0.0001), and for 17β-estradiol (P < 0.01) at 4 and 12 weeks. Efficacy was greater for both low-dose drospirenone/17β-estradiol combinations versus the lower-dose 17β-estradiol. Change in vaginal pH and vaginal maturation index showed significant improvements (with P values versus placebo of <0.0001 and P ≤ 0.0028, respectively), and exploratory analysis of the Clinical Global Impressions scale score indicated an overall satisfaction of women with active treatments. All active treatments were generally well tolerated with low rates of adverse event–related dropouts, and the safety profile of drospirenone/17β-estradiol in both low-dose combinations was consistent with previous studies.
Conclusions: Drospirenone 0.25 mg/17β-estradiol 0.5 mg is concluded to be the lowest dose with demonstrated efficacy in the treatment of postmenopausal women with moderate to severe vasomotor symptoms.
From the 1Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA; 2Bayer Pharma AG, Berlin, Germany; and 3Gynecology, Obstetrics, and Reproductive Medicine, University Medical School of Saarland, Homburg/Saar, Germany.
Received February 26, 2013; revised and accepted May 15, 2013.
Study synopsis available at: http://trialfinder.bayerscheringpharma.de/html/pdf/91493_Study_Synopsis_CTP.pdf.
The authors were not compensated and retained full editorial control over the content of this manuscript.
Funding/support: This study was supported by funding from Bayer Pharma AG (Berlin, Germany). Medical writing support for this manuscript was provided by Bill Wolvey of PAREXEL and funded by Bayer Pharma AG.
Financial disclosure/conflicts of interest: D.F.A. serves as a consultant to Abbott, Agile, Bayer, CHEMO, Depomed, Endoceutics, Ferring Pharmaceuticals, HRA Pharma, and Merck, and has previously served as a consultant to Schering-Plough, Organon, Shionogi, Teva, and Warner Chilcott. He has received grants from Abbott, Bayer Healthcare, Endoceutics, Pfizer, Teva, Warner Chilcott, and Watson Pharmaceuticals, and speaking honoraria from Bayer Healthcare, Besins, Ferring Pharmaceuticals, and Pfizer. The other authors are full-time employees of Bayer Pharma AG.
Address correspondence to: David F. Archer, MD, Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507-1912. E-mail: email@example.com