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Clinical Trial
. 2011 Apr;117(4):777-787.
doi: 10.1097/AOG.0b013e3182118ac3.

Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial

Jeffrey T Jensen  1 , Susanne Parke, Uwe Mellinger, Andrea Machlitt, Ian S Fraser
Affiliations
Clinical Trial

Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial

Jeffrey T Jensen et al. Obstet Gynecol. 2011 Apr.

Abstract

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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References

    1. Fraser IS, Langham S, Uhl-Hochgraeber K. Health-related quality of life and economic burden of abnormal uterine bleeding. Exp Rev Obstet Gynecol 2009;4:179–89.
    1. Liu Z, Doan QV, Blumenthal P, Dubois RW. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value Health 2007;10:183–94.
    1. Fraser IS, Critchley HO, Munro MG, Broder M; Writing Group for This Menstrual Agreement Process. A process designed to lead to international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril 2007;87:466–76.
    1. Fraser IS, Weisberg E, Minehan E, Johansson ED. A detailed analysis of menstrual blood loss in women using Norplant and Nestorone progestogen-only contraceptive implants or vaginal rings. Contraception 2000;61:241–51.
    1. Hale GE, Manconi F, Luscombe G, Fraser IS. Quantitative measurements of menstrual blood loss in ovulatory and anovulatory cycles in middle- and late-reproductive age and the menopausal transition. Obstet Gynecol 2010;115(2 pt 1):249–56.

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