One-year randomized study of the endometrial safety and bleeding pattern of 0.25 mg drospirenone/0.5 mg 17β-estradiol in postmenopausal women

Abstract

Objectives To investigate the long-term endometrial safety and bleeding pattern of the 0.25 mg drospirenone/0.5 mg 17β-estradiol (DRSP/E2) dose combination compared with 0.5 mg norethisterone acetate (NETA)/1.0 mg E2, in postmenopausal women.

Methods A total of 662 postmenopausal women aged between 40 and 65 years with an indication for hormone therapy verified by the investigator were randomized to participate in this 1-year, double-blind, active comparator-controlled study. The primary efficacy variable was the proportion of women with an endometrial biopsy assessment of ‘hyperplasia or worse’ at any time during or after 13 cycles of treatment.

Results No evaluable women in the DRSP/E2 or NETA/E2 groups had an endometrial biopsy result of ‘hyperplasia or worse’. The incidence of amenorrhea was higher in the DRSP/E2 group than the NETA/E2 group during months 1–3 (69.0% vs. 56.0%), with comparable amenorrhea rates of approximately 80% during months 10–12. Improvements in menopausal symptoms (exploratory efficacy variables) were similar in the two groups, while there were fewer women with treatment-related adverse events (18.4% vs. 25.6%) or adverse events leading to discontinuation of study drug (8.4% vs. 15.1%) in the DRSP/E2 group than the NETA/E2 group. There were no treatment-related thromboembolic or cardiovascular events in the DRSP/E2 group vs. two events in the NETA/E2 group.

Conclusions The low-dose, 0.25 mg DRSP/0.5 mg E2 dose combination met the criteria for endometrial safety and demonstrated a favorable risk/benefit profile in this 1-year, double-blind, randomized study of postmenopausal women.

Key words::

• DROSPIRENONE
• 17β-ESTRADIOL
• ENDOMETRIAL SAFETY
• BLEEDING PATTERN
• POSTMENOPAUSAL WOMEN

Conflict of interest Andrea Genazzani has received research support, acted as a consultant, and/or served on a speakers’ bureau for Abbott, Bayer, Besins, IBSA, Merck Sharp & Dohme, Pantarhei, Pfizer, Secure, Shionogi, Theramex, and Wyeth. Thomas Schmelter, Matthias Schaefers, Christoph Gerlinger, and Kerstin Gude are full-time employees of Bayer Pharma.

Sources of funding 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 was funded by Bayer Pharma AG. The authors were not compensated and retained full editorial control over the content of the manuscript.