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      Noncontraceptive benefits of the estradiol valerate/dienogest combined oral contraceptive: a review of the literature

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          Abstract

          Combined oral contraceptives formulated to include estradiol (E 2) have recently become available for the indication of pregnancy prevention. A combined estradiol valerate and dienogest pill (E 2V/DNG), designed to be administered using an estrogen step-down and a progestin step-up regimen over 26 days of active treatment followed by 2 days of placebo (26/2-day regimen), has also undergone research to assess the potential for additional noncontraceptive benefits. Randomized, placebo-controlled studies have demonstrated that E 2V/DNG is an effective treatment for heavy menstrual bleeding – a reduction in median menstrual blood loss approaching 90% occurs after 6 months of treatment. To date, E 2V/DNG is the only oral contraceptive approved for this indication. Comparator studies have also demonstrated a reduction in hormone withdrawal-associated symptoms in users of E 2V/DNG compared with a conventional 21/7-day regimen of ethinylestradiol/levonorgestrel. Other potential noncontraceptive benefits associated with E 2V/DNG, like improvement in dysmenorrhea, sexual function, and quality of life, are comparable with those associated with other combined oral contraceptives and are discussed further in this review.

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          Most cited references61

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          FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age.

          There is general inconsistency in the nomenclature used to describe abnormal uterine bleeding (AUB), in addition to a plethora of potential causes-several of which may coexist in a given individual. It seems clear that the development of consistent and universally accepted nomenclature is a step toward rectifying this unsatisfactory circumstance. Another requirement is the development of a classification system, on several levels, for the causes of AUB, which can be used by clinicians, investigators, and even patients to facilitate communication, clinical care, and research. This manuscript describes an ongoing process designed to achieve these goals, and presents for consideration the PALM-COEIN (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified) classification system for AUB, which has been approved by the International Federation of Gynecology and Obstetrics (FIGO) Executive Board as a FIGO classification system. Copyright © 2011. Published by Elsevier Ireland Ltd.
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            New progestagens for contraceptive use.

            The progestins have different pharmacologic properties depending upon the parent molecule, usually testosterone or progesterone (P), from which they are derived. Very small structural changes in the parent molecule may induce considerable differences in the activity of the derivative. In hormonal contraceptives, progestins represent the major agent designed for suppressing ovulation and are used in combination with estrogen (E) usually ethinyl-estradiol (EE). The development of new generations of progestins with improved selectivity profiles has been a great challenge. Steroidal and nonsteroidal progesterone receptor (PR) agonists have been synthesized as well, although the latter are still in a very early stage of development. Several new progestins, have been synthesized in the last two decades. These include dienogest (DNG), drospirenone (DRSP), Nestorone (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG). These new progestins have been designed to have no androgenic or estrogenic actions and to be closer in activity to the physiological hormone P. DRSP differs from the classic progestins as it is derived from spirolactone. It is essentially an antimineralocorticoid steroid with no androgenic effect but a partial antiandrogenic effect. The antiovulatory potency of the different progestins varies. TMG and NES are the most potent progestins synthesized to date, followed by two of the older progestins, keto-desogestrel (keto-DSG) and levonorgestrel (LNG). The new molecules TMG, DRSP and DNG also have antiandrogenic activity. Striking differences exist regarding the side effects among the progestins and the combination with EE leads to other reactions related to the E itself and whether the associated progestin counterbalances, more or less, the estrogenic action. The 19-norprogesterone molecules and the new molecules DRSP and DNG are not androgenic and, therefore, have no negative effect on the lipid profile. Given their pharmacological properties, it is likely that the new progestins may have neutral effects on metabolic or vascular risks. However, this hypothesis must be confirmed in large clinical trials.
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              Primary dysmenorrhea consensus guideline.

              Members of this consensus group were selected based on individual expertise to represent a range of practical and academic experience both in terms of location in Canada and type of practice, as well as subspecialty expertise along with general gynaecology backgrounds. The consensus group reviewed all available evidence through the English and French medical literature and available data from a survey of Canadian women. Recommendations were established as consensus statements. The final document was reviewed and approved by the Executive and Council of the SOGC. This document provides a summary of up-to-date evidence regarding the diagnosis, investigations, and medical and surgical management of dysmenorrhea. The resulting recommendations may be adapted by individual health care workers when serving women who suffer from this condition. Dysmenorrhea is an extremely common and sometimes debilitating condition for women of reproductive age. A multidisciplinary approach involving a combination of lifestyle, medications, and allied health services should be used to limit the impact of this condition on activities of daily living. In some circumstances, surgery is required to offer the desired relief. This guideline discusses the various options in managing dysmenorrhea. Patient information materials may be derived from these guidelines in order to educate women in terms of their options and possible risks and benefits of various treatment strategies. Women who find an acceptable management strategy for this condition may benefit from an improved quality of life.
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                Author and article information

                Journal
                Int J Womens Health
                Int J Womens Health
                International Journal of Women’s Health
                International Journal of Women's Health
                Dove Medical Press
                1179-1411
                2014
                02 August 2014
                : 6
                : 711-718
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Research Centre for Reproductive Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
                [2 ]Global Medical Affairs Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany
                [3 ]Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA
                Author notes
                Correspondence: Rossella E Nappi, Research Center for Reproductive Medicine, Obstetrics and Gynecology Unit, IRCCS Policlinico San Matteo Foundation, Piazzale Golgi 2, 27100 Pavia, Italy, Tel +39 0382 50 1561, Fax +39 0382 42 3233, Email renappi@ 123456tin.it
                Article
                ijwh-6-711
                10.2147/IJWH.S65481
                4128844
                c09e98a0-224d-4f07-b159-e73e92ea78bb
                © 2014 Nappi et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Obstetrics & Gynecology
                heavy menstrual bleeding,hormone withdrawal-associated symptoms,quality of life

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