estradiol-valerate-dienogest and Dysmenorrhea

The menstrual cycle is characterised by cyclical fluctuations in oestrogens, progesterone and androgens. Changes in hormone levels in the premenstrual phase with the decline in progesterone trigger a physiological reaction which culminates in menstruation. This process is accompanied in many women by various symptoms such as pelvic pain, headache, mood disorders and gastrointestinal discomfort. The aim of this article was to summarise the latest findings on the physiology and pathophysiology of menstruation and review the impact of shortening the hormone-free interval (HFI) on the health and wellbeing of women.. Menstruation can be viewed as an inflammatory event in which local and systemic effects produce symptoms in genital and extragenital regions of the body. The mast cells are the main mediator of this reaction. In women using hormonal contraceptives, menstrual bleeding is not biologically necessary and it may be advantageous to maintain more stable levels of oestrogens, progesterone and androgens throughout the cycle. New combined oral contraceptives (COCs) have been formulated with a progressively shorter HFI (24/4 and 26/2) than traditional 21/7 pills, with the rationale of reducing hormone withdrawal- associated symptoms. Several studies have shown the beneficial effects of these regimens, which reduce the inflammatory exposure of the female organism and thus have the capacity to increase the quality of life of women. A combination of estradiol valerate (E2V) and dienogest (DNG) is administered on the shortest 26/2 regimen. This regimen has a broad evidence base from randomised controlled trials that have examined the impact of E2V/DNG on symptoms and quality of life.. Shortening the HFI reduces the occurrence of bleeding-related inflammatory processes and subsequent physical and mental symptoms. The shortest interval with evidence of reproductive and sexual health benefits is provided by a 26/2 regimen.

Topics: Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Administration Schedule; Drug Combinations; Dysmenorrhea; Estradiol; Estrogens; Female; Gastrointestinal Diseases; Headache; Humans; Inflammation; Menstruation; Mood Disorders; Nandrolone; Pelvic Pain; Progesterone; Quality of Life

Pain relief of two different oral contraceptive pills (OCPs) in severe primary dysmenorrhoea (PD) was compared. Sixty-six nulliparous patients with severe PD requiring contraception were evaluated. Group 1 comprised 33 healthy controls. Patients with severe PD were divided into two groups. Patients in Group 2 were administered oestradiol valerate/dienogest and patients in Group 3 were administered ethinylestradiol/drospirenone. Doppler indices of both uterine arteries (left and right) including systolic/diastolicrates (S/D), pulsatility index (PI) and resistance index (RI) were measured, and a visual analogue scale (VAS) was applied to patients before treatment. VAS scores and Doppler indices were repeated after 3 months of OCP treatment and the changes in values were compared. The demographic and clinical characteristics of the patients were similar. The mean value of RI was significantly lower after therapy in Groups 2 and 3 in the right and left uterine arteries (p = .001 and p = .039, respectively). The clinical trial number was NCT03124524. Impact Statement What is already known on this subject: OCPs are the most appropriate treatment option for PD. There is no clear data about OCP containing dienogest for treatment in PD. Dienogest has been reported to be highly effective in the treatment of endometriosis and is also recommended as first-line therapy for pelvic pain-associated endometriosis. What the results of this study add: In this study, although there was no superiority in pain relief between the treatment groups, lower VAS scores and lower RI values of uterine arteries were seen after treatment. Both OCPs relieve pain in severe PD. There was no serious adverse effect in the patients. What the implications are of these findings for clinical practice and/or further research: Estradiol valerate/dienogest, which is a routinely prescribed drug for heavy menstrual bleeding in women who desire oral contraception, is as effective as ethinylestradiol/drospirenone in pain relief.

Topics: Adolescent; Adult; Androstenes; Contraceptives, Oral; Drug Combinations; Dysmenorrhea; Estradiol; Ethinyl Estradiol; Female; Humans; Nandrolone; Pain Measurement; Pelvic Pain; Prospective Studies; Pulsatile Flow; Treatment Outcome; Ultrasonography, Doppler; Uterine Artery; Young Adult

To demonstrate the superiority of estradiol valerate plus dienogest (E(2)V/DNG) over ethinylestradiol plus levonorgestrel (EE/LNG) in reducing the number of days with dysmenorrheic pain among women with primary dysmenorrhea.. In a phase IIIb trial conducted at 44 centers worldwide between April 2009 and November 2010, otherwise healthy women aged 14-50 years requesting contraception were randomized to daily oral administration of E(2)V/DNG (n = 253) or EE/LNG (n = 254) for three 28-daycycles. The primary efficacy variable was number of days with dysmenorrheic pain, the category of which (none, mild, moderate, severe) was self-assessed on a daily basis (irrespective of menstrual bleeding status) and recorded on diary cards. Notably, the women documented their pain as they experienced it before taking any (permitted) rescue medication.. Overall, 217 and 209 women receiving E(2)V/DNG and EE/LNG, respectively, completed the study. The mean ± SD change from baseline in number of days with dysmenorrheic pain was -4.6 ± 4.6 days and -4.2 ± 4.2 days for the E(2)V/DNG and EE/LNG groups, respectively (P = 0.34).. Both E(2)V/DNG and EE/LNG led to considerable relief of dysmenorrheic complaints among women with primary dysmenorrhea, decreasing the number of days with dysmenorrheic pain from baseline to a similar extent. ClinicalTrials.gov:NCT00909857.

Topics: Adolescent; Adult; Double-Blind Method; Drug Combinations; Dysmenorrhea; Estradiol; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Middle Aged; Nandrolone; Time Factors; Treatment Outcome; Young Adult

The progestin dienogest (DNG) given alone effectively reduces pelvic pain of women with endometriosis. It is not clear whether the same occurs when DNG is associated with estradiol (E2).. Patient preference prospective observational study.. Outpatient centre of university hospital.. 40 patients with endometriosis and menstrual pain.. 24-week treatment with a quadriphasic association of E2 valerate (E2V) and DNG or a nonsteroidal anti-inflammatory drug (NSAID) to be used only in case of pain (ketoprofene 200-mg tablets).. Menstrual pain and, when present, intermenstrual pain, and dyspareunia were investigated by means of a 10-cm visual analogue scale (VAS). Quality of life was investigated by the short form 36 (SF-36) of the health-related quality of life questionnaire.. Final study group consists of 34 patients, 19 in the E2V/DNG group and 15 in the NSAID group. After 24 weeks, no significant modification of menstrual pain, intermenstrual pain, dyspareunia, or SF-36 score was observed in the NSAID group. Treatment with E2V/DNG reduced the VAS score of menstrual pain by 61% (P < .0001). In the subgroups of women with intermenstrual pain or dyspareunia, E2V/DNG reduced these complaints by 65% (P = .013) and 52% (P = .016), respectively. The reduction in menstrual (P = .0001) and intermenstrual pain (p = 0.03) was significantly greater during E2V/DNG than NSAID. Quality of life improved during E2V/DNG (P = .0002), both in physical (P = .0003) and mental domains (P = .0065). Only a few minor adverse effects were described during E2V/DNG, and none caused withdrawal from treatment.. In patients with endometriosis and pelvic pain, the 24-week administration of the quadriphasic association of E2V/DNG decreases pelvic pain and improves quality of life.

Topics: Adult; Contraceptives, Oral, Hormonal; Drug Combinations; Dysmenorrhea; Endometriosis; Estradiol; Female; Hospitals, University; Humans; Italy; Nandrolone; Pain Measurement; Patient Preference; Pelvic Pain; Pilot Projects; Prospective Studies; Quality of Life; Surveys and Questionnaires; Time Factors; Treatment Outcome

Combined hormonal contraception might worsen migraine in sensitive women, especially during the free-hormone interval, and raise concerns about the vascular risk. The characteristics of a contraceptive pill containing estradiol valerate/dienogest (E2V/DNG) might be of potential benefit in women with menstrually related migraine (MRM) who choose to use oral contraception for birth control.. This was a prospective diary-based pilot study. Thirty-two women (age >35 years) [n=18 who had never used combined oral contraceptives (COCs) and n=14 who had previously used COCs] diagnosed with MRMs according to the International Headache Society criteria were included. During the observational period, women filled in a diary with the clinical characteristics of migraine attacks. After a three-cycle run-in period, each subject received a COC containing E2V/DNG (Qlaira®/Natazia®; Bayer HealthCare, Berlin, Germany) administered using an estrogen step-down and progestogen step-up approach. Follow-up evaluations were scheduled at the last cycle of run-in and at the third and sixth cycles of treatment.. The number of migraine attacks was significantly reduced at the third (p<.001) and sixth cycles (p<.001) in comparison with the run-in period. A similar result was evident for the duration (p<.001 at the third and p<.001 at the sixth cycle) as well as for the severity of head pain (p<.001 at the third and p<.001 at the sixth month). Indeed, a significantly lower number of analgesics were used at the third cycle (p<.001) in comparison with baseline, and a further decrease was evident at the sixth cycle (p<.001) in comparison with the third cycle of E2V/DNG use. Interestingly, duration and severity of head pain were significantly correlated with the number of days of dysmenorrhea at the third cycle (r=.89, p=.000 and r=.67, p=.02; respectively) and at the sixth cycle (r=.76, p=.000 and r=.62, p=.04; respectively) in women without complete remission of menstrual cramps during the study period.. The present diary-based pilot study indicates that the use of a pill containing EV2/DNG for six cycles has a positive effect in women with MRM and suggests an association between dysmenorrhea with COCs use as a potential feature of refractory head pain.

Topics: Adult; Analgesics; Body Mass Index; Contraceptives, Oral, Combined; Drug Combinations; Dysmenorrhea; Estradiol; Female; Humans; Italy; Menstruation; Migraine Disorders; Nandrolone; Pilot Projects; Prospective Studies; Treatment Outcome