Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial.
OBJECTIVE
The purpose of this multicenter, double-blind, randomized, parallel-group study was to determine the effect of thirteen 28-day cycles of drospirenone combined with estradiol, compared with estradiol alone, on the endometrium of postmenopausal women.


METHODS
Postmenopausal women not on hormone therapy but with an intact uterus were enrolled (N = 1,147); 1,142 were evaluated. Participants were randomly assigned to treatment with 1.0 mg of estradiol alone (E(2) monotherapy) or 1.0 mg of estradiol plus 0.5, 1.0, 2.0, or 3.0 mg of drospirenone (DRSP/E(2)). Endometrial biopsies were performed at baseline, at 7 months if indicated, and at study end in the 13th month. Safety was evaluated with peripheral blood samples for hematology, liver and renal function, and lipids, along with vital signs and interval medical evaluations.


RESULTS
When compared with estradiol alone, combinations of drospirenone and estradiol were effective in protecting against endometrial hyperplasia. The probability of hyperplasia was 0.060 (95% CI, 0.043-0.078) for the E(2) monotherapy group, 0.007 for the 2-mg DRSP/E(2) group, and nonsignificant for the remaining drospirenone/estradiol groups. Endometrial bleeding decreased in all treatment groups over time. The combination of drospirenone and E(2) relieved menopausal symptoms and resulted in improvements in health-related quality-of-life measures. There were no significant adverse events, and effects on triglycerides, total cholesterol, and high-density lipoprotein cholesterol were positive.


CONCLUSIONS
The use of drospirenone combined with estradiol provides protection against endometrial hyperplasia, reduces endometrial bleeding with time, and relieves menopausal symptoms. There were no safety issues and blood pressure was reduced in women with hypertension.
Archer
David F
DF
CONRAD Clinical Research Center, 601 Colley Avenue, Norfolk, VA 23507, USA. archerdf@evms.edu
Thorneycroft
Ian H
IH
Foegh
Marie
M
Hanes
Vladimir
V
Glant
Michael D
MD
Bitterman
Pincas
P
Kempson
Richard L
RL
D000328:Adult; D000368:Aged; D000736:Androstenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004338:Drug Combinations; D004714:Endometrial Hyperplasia / Q000517:prevention & control; D004717:Endometrium / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D052776:Female Urogenital Diseases / Q000517:prevention & control; D019584:Hot Flashes / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015999:Multivariate Analysis; D017060:Patient Satisfaction; D017698:Postmenopause; D011788:Quality of Life; D016896:Treatment Outcome; D014592:Uterine Hemorrhage / Q000517:prevention & control
D000736:Androstenes; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D004958:Estradiol; C035144:drospirenone