Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind Phase III trial.

Abstract

BACKGROUND:

This double-blind trial investigated the efficacy and safety of estradiol valerate/dienogest (E(2)V/DNG) for the treatment of heavy menstrual bleeding without recognizable organic pathology.

METHODS:

Otherwise healthy women with idiopathic heavy, prolonged or frequent menstrual bleeding, confirmed during a 90-day run-in phase, were randomized (2:1) according to a permuted-block, computer-generated schedule to E(2)V/DNG or placebo for 196 days at 34 centres in Europe and Australia. The primary efficacy end-point was the proportion of women with a 'complete' response (i.e. a return to 'menstrual normality') during a 90-day efficacy phase. Secondary end-points included changes in measured menstrual blood loss (MBL) and iron metabolism parameters.

RESULTS:

The intention-to-treat population comprised 231 women. The E(2)V/DNG response rate was much higher than with placebo (P < 0.0001). The mean reduction in MBL volume in E(2)V/DNG recipients was 69.4% (median 79.2%) versus 5.8% (median 7.4%) in placebo recipients. The between-treatment difference in MBL volume was 373 ml in favour of E(2)V/DNG (95% confidence interval 490, 255 ml; P < 0.0001). Significant improvements in iron metabolism parameters were observed with E(2)V/DNG but not placebo. Overall, 14 women (9.7%) treated with E(2)V/DNG and 5 (6.2%) treated with placebo prematurely discontinued treatment because of adverse events, headache being the most prevalent. Serious adverse events occurred in both the E(2)V/DNG and placebo groups (each n = 2).

CONCLUSIONS:

E(2)V/DNG is an effective treatment in women with heavy and/or prolonged menstrual bleeding without organic pathology. Further study of E(2)V/DNG compared with an active comparator is warranted. ClinicalTrials.gov identifier: NCT00307801.

• Authors: I S Fraser, T Römer, S Parke, S Zeun, U Mellinger, A Machlitt, J T Jensen
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 26 Issue 10 Pg. 2698-708 (Oct 2011) ISSN: 1460-2350 [Electronic] England
• PMID: 21784734 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Contraceptive Agents
• Contraceptives, Oral
• Placebos
• dienogest
• Estradiol
• Nandrolone

Topics

• Adult
• Australia
• Contraceptive Agents (therapeutic use)
• Contraceptives, Oral (therapeutic use)
• Double-Blind Method
• Estradiol (analogs & derivatives, therapeutic use)
• Europe
• Female
• Humans
• Menorrhagia (drug therapy)
• Menstruation (drug effects)
• Menstruation Disturbances (drug therapy)
• Nandrolone (analogs & derivatives, therapeutic use)
• Placebos
• Treatment Outcome