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

I. S. Fraser, T. Römer, S. Parke, S. Zeun, U. Mellinger, A. MacHlitt, Jeffrey Jensen

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Background This double-blind trial investigated the efficacy and safety of estradiol valerate/dienogest (E 2V/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 2V/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 2V/DNG response rate was much higher than with placebo (P <0.0001). The mean reduction in MBL volume in E 2V/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 2V/DNG (95 confidence interval 490, 255 ml; P <0.0001). Significant improvements in iron metabolism parameters were observed with E 2V/DNG but not placebo. Overall, 14 women (9.7) treated with E 2V/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 2V/DNG and placebo groups (each n = 2). Conclusions E 2V/DNG is an effective treatment in women with heavy and/or prolonged menstrual bleeding without organic pathology. Further study of E 2V/DNG compared with an active comparator is warranted.

Original languageEnglish (US)
Pages (from-to)2698-2708
Number of pages11
JournalHuman Reproduction
Volume26
Issue number10
DOIs
StatePublished - Oct 2011

Fingerprint

Oral Contraceptives
Placebos
Hemorrhage
Blood Volume
Therapeutics
Iron
Pathology
Headache
estradiol valerate-dienogest
Appointments and Schedules
Confidence Intervals
Safety
Population

Keywords

  • Dienogest
  • estradiol valerate
  • heavy and/or prolonged menstrual bleeding
  • oral contraceptive
  • RCT

ASJC Scopus subject areas

  • Rehabilitation
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

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. / Fraser, I. S.; Römer, T.; Parke, S.; Zeun, S.; Mellinger, U.; MacHlitt, A.; Jensen, Jeffrey.

In: Human Reproduction, Vol. 26, No. 10, 10.2011, p. 2698-2708.

Research output: Contribution to journalArticle

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abstract = "Background This double-blind trial investigated the efficacy and safety of estradiol valerate/dienogest (E 2V/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 2V/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 2V/DNG response rate was much higher than with placebo (P <0.0001). The mean reduction in MBL volume in E 2V/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 2V/DNG (95 confidence interval 490, 255 ml; P <0.0001). Significant improvements in iron metabolism parameters were observed with E 2V/DNG but not placebo. Overall, 14 women (9.7) treated with E 2V/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 2V/DNG and placebo groups (each n = 2). Conclusions E 2V/DNG is an effective treatment in women with heavy and/or prolonged menstrual bleeding without organic pathology. Further study of E 2V/DNG compared with an active comparator is warranted.",
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AU - MacHlitt, A.

AU - Jensen, Jeffrey

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N2 - Background This double-blind trial investigated the efficacy and safety of estradiol valerate/dienogest (E 2V/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 2V/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 2V/DNG response rate was much higher than with placebo (P <0.0001). The mean reduction in MBL volume in E 2V/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 2V/DNG (95 confidence interval 490, 255 ml; P <0.0001). Significant improvements in iron metabolism parameters were observed with E 2V/DNG but not placebo. Overall, 14 women (9.7) treated with E 2V/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 2V/DNG and placebo groups (each n = 2). Conclusions E 2V/DNG is an effective treatment in women with heavy and/or prolonged menstrual bleeding without organic pathology. Further study of E 2V/DNG compared with an active comparator is warranted.

AB - Background This double-blind trial investigated the efficacy and safety of estradiol valerate/dienogest (E 2V/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 2V/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 2V/DNG response rate was much higher than with placebo (P <0.0001). The mean reduction in MBL volume in E 2V/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 2V/DNG (95 confidence interval 490, 255 ml; P <0.0001). Significant improvements in iron metabolism parameters were observed with E 2V/DNG but not placebo. Overall, 14 women (9.7) treated with E 2V/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 2V/DNG and placebo groups (each n = 2). Conclusions E 2V/DNG is an effective treatment in women with heavy and/or prolonged menstrual bleeding without organic pathology. Further study of E 2V/DNG compared with an active comparator is warranted.

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