Major Finding: Complete resolution of abnormal menstrual symptoms was achieved in 44% of those receiving an oral contraceptive containing estradiol valerate/dienogest vs. 4% of those given placebo.
Data Source: A multinational, double-blind phase III trial of 135 women.
Disclosures: The study was funded by Bayer Schering Pharma AG, which is developing E2V/DNG. Dr. Jensen has received research support from Bayer and Warner-Chilcott, and served as consultant for Bayer and Schering Plough. His coauthors disclosed employment with Bayer Schering and consultant roles with Bayer.
ATLANTA — An oral contraceptive known in Europe as Qlaira significantly reduced menstrual blood loss in women suffering from idiopathic heavy and/or prolonged menstrual bleeding, in a multinational, double-blind phase III trial.
Among 135 evaluable women, complete resolution of abnormal menstrual symptoms was achieved in 44% of those receiving the oral contraceptive containing estradiol valerate/dienogest (E2V/DNG) vs. 4% of those given placebo. The mean change in menstrual blood loss volume, as quantified using the alkaline hematin method, was −353 mL in the E2V/DNG arm vs. 130 mL in the placebo arm (P less than .0001).
The dramatic reduction in blood loss was apparent in 3 months, and was accompanied by improvements in iron metabolism parameters, said lead researcher Dr. Jeffrey T. Jensen, professor of obstetrics and gynecology at the Oregon Health and Science University in Portland.
Significant improvements were observed at 196 days with E2V/DNG vs. placebo in the mean change from baseline in the hematocrit (1.4% vs. −0.05%), ferritin (2.9 ng/mL vs. −0.4 ng/mL), and hemoglobin (0.6 g/dL vs. 0.1 g/dL) levels.
E2V/DNG was approved for contraception in Europe under the trade name Qlaira in 2009, and may become available in 2010 in the United States where dual indications for contraception and heavy menstrual bleeding are being discussed, Dr. Jensen said at the annual meeting of the American Society for Reproductive Medicine. Dienogest is available in Europe as a single-agent pill to treat endometriosis, and in combination with ethinyl estradiol for contraception.
During a discussion of the study, audience members questioned the lack of an active comparator in the study and the high number of patients excluded from analysis. Dr. Jensen said that it was a weakness not to have an active comparator, but that the study design was required by the Food and Drug Administration. Furthermore, unpublished data from a third trial showed a similar reduction in bleeding at 3 months with E2V/DNG and the approved levonorgestrel-releasing intrauterine system (LNG-IUS) and a better response at 6 months with LNG-IUS.
“Having placebo-controlled data is very useful as far as getting a benchmark, and there's lots of women out there that aren't currently using any other products,” he said. “Now whether this is a better treatment than other oral contraceptives, we don't know,” he said.
A comparative trial conducted by one of Dr. Jensen's coinvestigators in 798 healthy women seeking contraception, reported significantly fewer bleeding/spotting days among women given E2V/DNG than those given ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG): 17.3 vs. 21.5 days (P less than .0001). No unintended pregnancies occurred with E2V/DNG and only one occurred with EE/LNG, while adverse drug reactions occurred in 10% vs. 8.5% of women (Contraception 2009;80:436-4).