NEW YORK – Women with heavy or prolonged periods benefit from treatment with an oral contraceptive formulation that combines step-down estradiol valerate with step-up dienogest, a report in the April issue of Obstetrics & Gynecology indicates.
Dr. Jeffrey T. Jensen, with the Oregon Health & Science University, Portland, and colleagues observe that some studies indicate that oral contraceptive pills (OCPs) can reduce heavy menstrual bleeding. “The properties of an OCP combining estradiol (E2) valerate (which circulates as E2) and dienogest (a progestin with high endometrial potency) in an estrogen step-down and progestin step-up regimen was hypothesized to be beneficial in this setting.”
To test this, the researchers conducted a double-blind, placebo controlled trial involving 190 women with heavy, frequent or prolonged menstrual bleeding objectively confirmed during a run-in phase. Then, 120 of the women were assigned to E2 valerate plus dienogest while 70 were given placebo.
On an intention-to-treat basis, menstrual blood loss was at least halved at the end of the study compared to the run-in phase in 29.2% of the women on the OCP compared to 2.9% of those in the placebo group.
In an analysis of participants with complete data, the corresponding rates were 43.8% compared to 4.2%.
“The mean reduction in menstrual blood loss with E2 valerate and dienogest from the run-in phase to the efficacy phase was substantial (-353 mL; mean -64.2%) and significantly greater than that in placebo recipients (-130 mL; mean -7.8%; p<0.001),” the researchers report. As for tolerability, 34.5% of E2/dienogest recipients and 15.2% of placebo recipients experienced an adverse event probably related to treatment. The most frequent events were acne (4.2%), breast pain (3.4%), breast tenderness (2.5%), dysmenorrhea (2.5%), and headache (2.5%) in active treatment group, and headache (6.1%) and nausea (3.0%) in the placebo group. “The unique dosing regimen (estrogen step-down and progestogen step-up) and the hormonal components of this novel OCP may account for its ability to reduce heavy menstrual bleeding,” Dr. Jensen and colleagues comment. They conclude that for patients with abnormal menstrual bleeding, “E2 valerate and dienogest provides an important new oral, daily, self-administered noninvasive and fertility-sparing treatment option that is reversible and provides reliable contraceptive efficacy.” The study was supported by Bayer HealthCare Pharmaceuticals. “Some readers will view the paper with suspicion because three of the coauthors are employees of the pharmaceutical company that funded the trial,” Dr. James O. Drife comments in an editorial. However, adds Dr. Drife, from the University of Leeds School of Medicine, UK, “The study has been rigorously scrutinized by the journal’s reviewers. It is well designed and adequately powered, and uses both subjective and objective methods of blood-loss assessment.” He concludes, “Surgical treatment for menstrual disorders remains commonplace in all developed countries, and a safe medical alternative for some women is to be welcomed.” Obstet Gynecol 2011;117:777–787.
