Effective treatment of heavy menstrual bleeding with estradiol valerate and
dienogest: a randomized controlled trial.
Author(s): Jensen JT, Parke S, Mellinger U, Machlitt A, Fraser IS.
Affiliation(s): Department of Obstetrics and Gynecology, Oregon Health & Science University,
Portland, Oregon 97239, USA. jensenje@ohsu.edu
Publication date & source: 2011, Obstet Gynecol. , 117(4):777-87
OBJECTIVE: To estimate the efficacy of a fixed estrogen step-down and progestin
step-up 28-day estradiol (E2) valerate and dienogest oral contraceptive regimen
in women with heavy menstrual bleeding, prolonged menstrual bleeding, or heavy
and prolonged menstrual bleeding without organic pathology.
METHODS: This double-blind, placebo-controlled study randomized women aged 18
years or older with prolonged, frequent, or heavy menstrual bleeding, objectively
confirmed during a 90-day run-in phase, to treatment with E2 valerate and
dienogest or placebo (2:1) for 196 days. Data from the last 90 days of treatment
and the run-in phase were compared. The primary variable was the "complete
response" rate (complete resolution of qualifying abnormal menstrual symptoms,
including a 50% or greater reduction in pretreatment menstrual blood loss volume
in women with heavy menstrual bleeding). Secondary variables included objective
changes in menstrual blood loss volume (alkaline hematin methodology) and iron
metabolism parameters. Overall, 180 women were needed to provide 90% power.
RESULTS: There were no marked differences in the characteristics of E2 valerate
and dienogest (n=120) and placebo (n=70) recipients. The proportion of "complete
responders" in the evaluable group was significantly higher in E2 valerate and
dienogest (35/80; 43.8%) compared with placebo (2/48, 4.2%, P<.001) recipients.
The mean [standard deviation] reduction in menstrual blood loss with E2 valerate
and dienogest from the run-in phase to the efficacy phase was substantial (-353
mL [309 mL]; mean -64.2%; median -70.6%) and significantly greater than that in
placebo recipients (-130 mL [338 mL]; mean -7.8%; median -18.7%; P<.001).
Significant improvements in hemoglobin, hematocrit, and ferritin were seen with
E2 valerate and dienogest, but not with placebo.
CONCLUSION: Oral E2 valerate and dienogest was highly effective compared with
placebo in the treatment of women with heavy menstrual bleeding, prolonged
menstrual bleeding, or heavy and prolonged menstrual bleeding without organic
pathology.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov,
NCT00293059.
LEVEL OF EVIDENCE: I.
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