estradiol-valerate-dienogest and Menorrhagia

The new estradiol valerate and dienogest oral contraceptive pill recently received U.S. Food and Drug Administration (FDA) approval to treat heavy menstrual bleeding in women without diagnosed uterine conditions.This oral contraceptive formulation combines estradiol valerate, which is metabolically identical to natural estradiol, with the potent new progestin, dienogest. The four-phasic pill is effective for pregnancy prevention and leads to significantly decreased menstrual bleeding among women with heavy periods, and shorter and lighter periods among women with normal periods. Studies indicate that this formulation may be associated with decreased hepatic activation compared to contraceptive pills that contain ethinyl estradiol. However, whether these findings translate to a decreased risk of thrombotic events has not been determined, and the pill carries the same contraindications as all other combined hormonal contraceptives.At least 10-15% of women suffer from heavy menstrual bleeding, defined as ≥80 mL of blood loss per cycle. In large clinical trials of women with heavy menstrual bleeding, the estradiol valerate and dienogest pill decreased blood loss volume by a median of 81%.Women with heavy menstrual bleeding treated with this contraceptive pill can expect a significant reduction in bleeding after just one cycle of use. This therapy leads to a decrease in bleeding that may be greater than that achieved by different oral contraceptive pills or other medical therapies, including tranexamic acid and nonsteroidal anti-inflammatory drugs.

Topics: Contraceptives, Oral; Drug Combinations; Estradiol; Female; Humans; Menorrhagia; Nandrolone

Since ethinyl estradiol is a potent activator of hepatic enzymes, the use of natural estradiol (E2) has been studied; but, until recently, bleeding control has hampered development of an E2 pill.. A historical review of oral contraceptive development leading to the successful design of an estradiol pill. Pharmacology, mechanism of action and clinical trials of contraceptive efficacy and bleeding profile of the estradiol valerate/dienogest (E2V/DNG) pill are reviewed. Details of two placebo-controlled treatment trials of the E2V/DNG pill in women with heavy menstrual bleeding are discussed. All available literature was searched using pubMed and additional data were obtained from published abstracts.. Information on the novel features and indications for the E2V/DNG pill.. The dynamic-dosing E2V/DNG oral contraceptive pill provides a highly effective contraceptive option with an adjusted Pearl Index (method failure) of 0.51 (upper limit of 95% CI 0.97) and unadjusted Pearl Index (user failure) of 1.01 (1.59) for women aged 18-35 years. In addition, two large randomized controlled trials have demonstrated that E2V/DNG provides effective treatment for women with heavy menstrual bleeding.

Topics: Adolescent; Adult; Clinical Trials as Topic; Contraceptives, Oral, Combined; Drug Combinations; Drug Design; Estradiol; Female; Humans; Menorrhagia; Nandrolone; Pregnancy; Pregnancy, Unplanned; Young Adult

To investigate the efficacy and safety of estradiol valerate (EV)/dienogest (DNG) for the management of heavy menstrual bleeding (HMB) in Asian and non-Asian women desiring contraception.. In this multicenter, double-blind, phase III study, women were randomized 2:1 to receive EV/DNG or placebo tablets daily for seven 28-day cycles. The primary endpoint was the absolute change in menstrual blood loss (MBL) volume between the run-in and efficacy phases (90 days each). Secondary endpoints included the proportion of women with successful treatment (i.e., no episodes of MBL ≥80 mL and a decrease of <50% in MBL), percent change in MBL from the run-in phase, and change in hemoglobin and serum ferritin levels. Adverse events (AEs) were monitored throughout the study.. Of the 341 women (mean age 34.7 ± 7.7 years; 309 Asians, 32 non-Asians) randomized, 270 completed the study. Mean reduction in MBL volume from run-in phase was significantly greater with EV/DNG than placebo (366.75 mL vs. 149.14 mL; p < 0.0001), with ∼52% and 12% of women, respectively, experiencing successful treatment. Percent decrease in MBL volume from the run-in phase was significantly greater with EV/DNG than placebo (63.5% vs. 24.8%; p < 0.0001). Hemoglobin and serum ferritin levels were increased with EV/DNG compared with placebo. Study drug-related AEs were reported in 16.3% and 8.2% of women with EV/DNG and placebo, respectively, none of which were of severe intensity.. EV/DNG may be a safe and effective option in the treatment of HMB in Asian and non-Asian women who desire contraception.

Topics: Adult; Contraceptives, Oral; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Ferritins; Hemoglobins; Humans; Menorrhagia; Menstrual Cycle; Nandrolone; Treatment Outcome

This study demonstrates a robust and thorough trial design leading to accurate and objective data collection. We recommend that future studies investigating heavy menstrual bleeding (HMB) should follow, and improve upon, this rigorous approach to menstrual trial data collection, not only to validate clinical results but also to improve the techniques used to acquire these results. We propose that the state-of-the-art methodology described here be used as the basis for new guidelines for the implementation of clinical trials in the area of HMB.

Topics: Contraceptives, Oral; Double-Blind Method; Drug Combinations; Estradiol; Female; Follow-Up Studies; Humans; Internationality; Menorrhagia; Nandrolone

To quantify the change in work productivity and activities of daily living in North American women with heavy menstrual bleeding (HMB) treated with estradiol valerate/dienogest (E2V/DNG; Qlaira(®)/Natazia(®)) compared to placebo.. Women in the United States and Canada, aged 20-53 years with an objective diagnosis of HMB and no recognizable anatomical pathology, were treated with E2V/DNG or placebo for seven cycles (196 days). Main outcome measures included work productivity (i.e., productivity while at work) and activities of daily living measured using a modified Work Productivity and Activity Impairment Questionnaire (mWPAI) on a Likert scale from 0 to 10 (higher values denote higher impairment levels).. In both countries, significant improvement was observed between baseline and end of treatment in work productivity and activities of daily living impairment. The improvements in work productivity and activities of daily living with E2V/DNG treatment relative to placebo ranged from 37.2% to 39.2% across both countries. Monthly gains due to E2V/DNG treatment (net of placebo improvement) associated with improvement in work productivity were estimated to be US$80.2 and Can$70.8 (US$58.5) and those associated with improvement in activities of daily living were estimated to be US$84.9 and Can$73.5 (US$60.7).. E2V/DNG was shown to have a consistent positive impact on work productivity and activities of daily living in U.S. and Canadian women with HMB. In addition, these improvements in work productivity and activities of daily living were associated with a reduction in HMB-related monetary burden compared to the placebo group.

Topics: Activities of Daily Living; Adult; Contraceptives, Oral, Hormonal; Double-Blind Method; Drug Combinations; Efficiency; Estradiol; Female; Humans; Menorrhagia; Middle Aged; Nandrolone; Treatment Outcome; Work; Young Adult

To compare the effectiveness and costs associated with first-line medical treatments for chronic heavy menstrual bleeding (HMB) in Spain.. A cost-effectiveness analysis was conducted comparing the levonorgestrel-releasing intrauterine system (LNG-IUS) with the estradiol valerate/dienogest multiphase oral contraceptive (E2V/DNG), combined oral contraceptives (COC) and progestins (PROG). Study patients were fertile women diagnosed with HMB who initially wished to remain fertile. A Markov model based on reported clinical data and the opinion of a panel of experts was used. The time horizon of the analysis was 5 years. The analysis was conducted from the perspective of the Spanish National Health System (NHS), discounting both costs (€ 2013) and future effects at an annual rate of 3%. One-way sensitivity analyses and probabilistic sensitivity analysis were performed to test the robustness of the results.. In the analysis at 5 years, the LNG-IUS was associated with a gain of 0.67, 2.22, and 3.53 symptoms free months (SFM) compared with E2V/DNG, COC and PROG, respectively. LNG-IUS contributed more quality-adjusted life months (QALM) than the other treatment alternatives (+1.74 vs. E2V/DNG, +3.33 vs. COC +3.53 vs. PROG). First-line LNG-IUS treatment resulted in savings of € 583, € 988, and € 1891 vs. E2V/DNG, COC and PROG, respectively. These cost benefits, coupled with the greater clinical benefits in terms of SFM and QALM, show that LNG-IUS is the dominant option (less costly and more effective).. LNG-IUS is the medical treatment of choice and cost-saving option for the control of HMB in Spain.

Topics: Contraceptives, Oral, Combined; Cost-Benefit Analysis; Drug Combinations; Estradiol; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Menorrhagia; Models, Theoretical; Nandrolone; Spain

The study was conducted to assess the efficacy of estradiol valerate/dienogest (E₂V/DNG) administered using an estrogen step-down and progestogen step-up approach in a 28-day regimen in the treatment of heavy menstrual bleeding (HMB) using clinical end points allowing E₂V/DNG to be compared with other available medical therapies.. This was a pooled analysis of data from two identically designed randomized, placebo-controlled, multiple center studies conducted in Europe, Australia and North America that assessed the effectiveness of E₂V/DNG in reducing menstrual blood loss (MBL) in women with HMB. Women aged ≥ 18 years with objectively confirmed HMB were randomized to E₂V/DNG (n=220) or placebo (n=135) for seven treatment cycles. Outcomes analyzed included absolute reduction in MBL from baseline, proportion of women successfully treated (defined as MBL below 80 mL and ≥ 50% reduction in MBL), proportion with MBL below 80 mL and proportion with ≥ 50% reduction in MBL from baseline.. At study end, 63.6% and 11.9% of patients were successfully treated with E₂V/DNG and placebo, respectively, with 68.2% and 15.6% of women with MBL below 80 mL, and 70.0% and 17.0% with MBL reduction ≥ 50% (all p<.001).. E₂V/DNG is highly effective for the treatment of HMB and is associated with a high rate of treatment success.

Topics: Adolescent; Adult; Androgens; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Double-Blind Method; Drug Combinations; Estradiol; Estrogens; Female; Humans; Intention to Treat Analysis; Menorrhagia; Middle Aged; Nandrolone; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult