Vaginal bleeding/spotting with conjugated estrogens/bazedoxifene, conjugated estrogens/medroxyprogesterone acetate, and placebo

ABSTRACT

Objective: In the 1-year phase 3 Selective estrogens, Menopause, And Response to Therapy-5 trial, cumulative amenorrhea rates with conjugated estrogens/bazedoxifene (CE/BZA) were similar to placebo and higher than with conjugated estrogens/medroxyprogesterone acetate (CE/MPA). This post hoc analysis reports bleeding/spotting rates in 4-week intervals (cycles) and 3-month intervals (quarters) with these therapies and the percentage of cases attributable to spotting only.

Methods: Generally healthy postmenopausal women with menopausal symptoms recorded vaginal bleeding/spotting in daily diaries while receiving CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, CE 0.45 mg/MPA 1.5 mg, or placebo.

Results: A total of 1596 women in the modified intent-to-treat population contributed data. Incidence of bleeding/spotting was significantly (p < 0.001) lower with CE 0.45 mg/BZA 20 mg (0.54‒4.44%), CE 0.625 mg/BZA 20 mg (1.26‒5.02%), and placebo (1.55‒4.82%) compared with CE 0.45 mg/MPA 1.5 mg (8.81‒25.63%) in all 4-week cycles. Each quarter, <10% of women taking CE/BZA doses or placebo had bleeding/spotting, significantly (p < 0.001) less than the 21–36% with CE 0.45 mg/MPA 1.5 mg. Odds ratio for bleeding/spotting with CE 0.45 mg/BZA 20 mg vs CE 0.45 mg/MPA 1.5 mg was 0.1 in each quarter (95% CI, Q1–Q3: 0.1–0.2; Q4: 0.1–0.3). Across all treatments, most (88–100%) bleeding/spotting cases were spotting only. Mean days of bleeding/spotting were <1 per quarter with CE/BZA doses and placebo, which was significantly (p < 0.01) less than the 3–5 days per quarter with CE/MPA.

Conclusions: Bleeding/spotting with CE/BZA treatment was similar to placebo and significantly less frequent than with CE/MPA treatment. Most cases were spotting only across all treatments.

KEYWORDS:

• Vaginal bleeding
• spotting
• postmenopause
• conjugated estrogens/bazedoxifene
• conjugated estrogens/medroxyprogesterone acetate

Acknowledgments

The authors thank the original SMART-5 participants and investigators, as well as Ellen Meier and Ching-Ray Yu for their assistance with the post hoc data analyses.

Declaration of interest

R Kagan has served as a consultant/advisory board member for Allergan, AMAG Pharmaceuticals, Amgen, Palatin Technologies, Pfizer, Valeant, TherapeuticsMD, and Copper Surgical; 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 Pfizer, AMAG Pharmaceuticals, and Valeant; and has received editorial writing support from Pfizer, and TherapeuticsMD. P Abreu and E Andrews are employees and shareholders of Pfizer Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. A peer reviewer on this manuscript has acted as an investigator and author on BZA-monotherapy studies and has acted as consultant/speaker for Pfizer. Some topics included amongst others the CE/BZA combination, was never directly involved in the CE/BZA development.

Additional information

Funding

This study was sponsored by Pfizer Inc. Medical writing support was provided by Lauren Cerruto and Diane M. Sloan, PharmD, of Peloton Advantage and was funded by Pfizer Inc.