title: 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: OBJECTIVE
  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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Pisa, Pisa, Italy.
authors.forename: A R
authors.initials: AR
authors.lastname: Genazzani
authors.forename: T
authors.initials: T
authors.lastname: Schmelter
authors.forename: M
authors.initials: M
authors.lastname: Schaefers
authors.forename: C
authors.initials: C
authors.lastname: Gerlinger
authors.forename: K
authors.initials: K
authors.lastname: Gude
mesh_terms: D000328:Adult; D000368:Aged; D000736:Androstenes / Q000008:administration & dosage* / Q000009:adverse effects*; D001706:Biopsy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016896:Treatment Outcome; D014592:Uterine Hemorrhage / Q000453:epidemiology
chemical_list: D000736:Androstenes; D004958:Estradiol; C035144:drospirenone