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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. 2011

I S Fraser, and T Römer, and S Parke, and S Zeun, and U Mellinger, and A Machlitt, and J T Jensen
Department of Obstetrics and Gynaecology, Central Clinical School, D02 - QEII Research Institute for Mothers and Infants, University of Sydney, Sydney, NSW 2006, Australia. i_fraser@med.usyd.edu.au

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.

UI MeSH Term Description Entries
D008595 Menorrhagia Excessive uterine bleeding during MENSTRUATION. Hypermenorrhea,Heavy Menstrual Bleeding,Heavy Periods,Heavy Period,Menstrual Bleeding, Heavy
D008598 Menstruation The periodic shedding of the ENDOMETRIUM and associated menstrual bleeding in the MENSTRUAL CYCLE of humans and primates. Menstruation is due to the decline in circulating PROGESTERONE, and occurs at the late LUTEAL PHASE when LUTEOLYSIS of the CORPUS LUTEUM takes place.
D008599 Menstruation Disturbances Variations of MENSTRUATION which may be indicative of disease. Hypomenorrhea,Menstruation Disorders,Menstruation, Retrograde,Polymenorrhea,Irregular Menses,Irregular Menstruation,Menstrual Irregularities,Menstrual Irregularity,Disorder, Menstruation,Disorders, Menstruation,Disturbance, Menstruation,Disturbances, Menstruation,Irregularity, Menstrual,Menses, Irregular,Menstruation Disorder,Menstruation Disturbance,Menstruation, Irregular,Retrograde Menstruation
D009277 Nandrolone C18 steroid with androgenic and anabolic properties. It is generally prepared from alkyl ethers of ESTRADIOL to resemble TESTOSTERONE but less one carbon at the 19 position. 19-Nortestosterone,Estrenolone,Norandrostenolone,Nortestosterone,17-Hydroxy-Estr-4-Ene-3-One,17beta-Hydroxy-19-Nor-4-Androsten-3-One,17beta Hydroxy 19 Nor 4 Androsten 3 One
D010919 Placebos Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. Sham Treatment
D003270 Contraceptive Agents Chemical substances that prevent or reduce the probability of CONCEPTION. Contraceptive,Contraceptive Effect,Contraceptive Effects,Contraceptives,Agents, Contraceptive,Effect, Contraceptive,Effects, Contraceptive
D003276 Contraceptives, Oral Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Low-Dose Oral Contraceptive,Oral Contraceptive,Oral Contraceptives,Oral Contraceptives, Low-Dose,Oral Contraceptives, Phasic,Contraceptive, Low-Dose Oral,Contraceptive, Oral,Contraceptives, Low-Dose Oral,Contraceptives, Phasic Oral,Low Dose Oral Contraceptive,Low-Dose Oral Contraceptives,Oral Contraceptive, Low-Dose,Oral Contraceptives, Low Dose,Phasic Oral Contraceptives
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D005060 Europe The continent north of AFRICA, west of ASIA and east of the ATLANTIC OCEAN. Northern Europe,Southern Europe,Western Europe

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