Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest

Ian S Fraser, Susanne Parke, Uwe Mellinger, Andrea Machlitt, Marco Serrani, Jeffrey Jensen, Ian S Fraser, Susanne Parke, Uwe Mellinger, Andrea Machlitt, Marco Serrani, Jeffrey Jensen

Abstract

Objectives: To evaluate the efficacy of oestradiol valerate/dienogest (E2V/DNG) for the treatment of heavy and/or prolonged menstrual bleeding without organic pathology based on the analysis of data from two identically designed double-blind, randomised studies.

Methods: Women aged ≥ 18 years with heavy and/or prolonged menstrual bleeding were randomised to E2V/DNG (n = 269) or placebo (n = 152) for 196 days. Objective changes in menstrual blood loss (MBL) volume were assessed using the alkaline haematin method.

Results: After six months of treatment, median MBL decreased by 88% with E2V/DNG compared with 24% with placebo. The greatest reduction was achieved at the first withdrawal bleed after treatment initiation and it was sustained with no loss of effect throughout treatment.

Conclusion: E2V/DNG was more effective than placebo in reducing MBL in women with heavy and/or prolonged menstrual bleeding without organic pathology. The reduction was largely achieved as early as the first withdrawal bleed, with further gradual improvement throughout treatment.

Figures

Figure 1
Figure 1
Pooled flow of participants through two studies, one conducted in North America and the other in Europe and Australia.
Figure 2
Figure 2
Median menstrual blood loss (MBL) by treatment cycle in patients treated with oestradiol valerate/dienogest (E2V/DNG) and placebo in (a) the intent-to-treat (ITT) population and (b) the subgroup of women with excessively heavy menstrual bleeding (defined as MBL greater than 80 ml at baseline; n = 227 for E2V/DNG and n = 136 for placebo). *For comparative purposes, baseline was calculated as (MBL volume during the 90-day run-in phase/90) × 28. **MBL observed during treatment cycle 1 represents the physiological menstrual bleeding (which triggers the start of treatment) plus any intermenstrual bleeding that may have occurred. ***Total blood loss during 28-day treatment cycles.
Figure 3
Figure 3
Percentage change in menstrual blood loss (MBL) volume from baseline (90-day run-in phase) to the efficacy phase (90-day efficacy phase) experienced by the proportion of women (intent-to-treat [ITT]).
Figure 4
Figure 4
Absolute and relative reduction in menstrual blood loss (MBL) according to baseline MBL in the intent-to-treat (ITT) population. Data presented as (a) median reduction in MBL volume from baseline to treatment cycle 7 and (b) median percentage reduction from baseline to treatment cycle 7

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