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      Alternative Oral Agents in Prophylaxis and Therapy of Uterine Fibroids—An Up-to-Date Review

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          Abstract

          Uterine fibroids (UFs) are the most common tumors of the female genital tract. The effect of UFs on the quality of life and the overall cost of treatment are significant issues worldwide. Tumor size and location are the two specific factors which influence the occurrence of symptoms, the need for, and method of, treatment (some tumors require surgery while some can be treated with selected drugs). Primary prevention and treatment of early UF disease are worthy goals that might have a great impact on health care systems. Several treatments and prophylactic methods can be used in this endeavor. This publication presents current data about lesser-known substances which may have a beneficial effect on the treatment or prophylaxis of UFs and can be administered orally, serving as an alternative to (or complement of) surgery or selective progesterone receptor modulators (SPRMs). Early prevention and treatment of UFs in women from high-risk groups should be our priority. Innovative forms of UF management are under intensive investigation and may be promising options in the near future. Many of them evaluated vitamin D, paricalcitol, epigallocatechin gallate (EGCG), elagolix, aromatase inhibitors (AIs), and cabergoline and deemed them to be safe and effective. The next step in such projects should be properly constructed randomized control trials (RCTs), carried out by successive phases.

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          Most cited references135

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          High cumulative incidence of uterine leiomyoma in black and white women: Ultrasound evidence

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            Uterine fibroids.

            E Stewart (2001)
            Uterine leiomyomas (fibroids or myomas), benign tumours of the human uterus, are the single most common indication for hysterectomy. They are clinically apparent in up to 25% of women and cause significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pressure or pain, and, in rare cases, reproductive dysfunction. Thus, both the economic cost and the effect on quality of life are substantial. Surgery has been the mainstay of fibroid treatment, and various minimally invasive procedures have been developed in addition to hysterectomy and abdominal myomectomy. Formation of new leiomyomas after these conservative therapies remains a substantial problem. Although medications that manipulate concentrations of steroid hormones are effective, side-effects limit long-term use. A better approach may be manipulation of the steroid-hormone environment with specific hormone antagonists. There has been little evidence-based evaluation of therapy. New research into the basic biology of these neoplasms may add new treatment options for the future as the role of growth factors and genetic mutations in these tumours are better understood.
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              Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study.

              Green tea polyphenols have been extensively studied as cardiovascular disease and cancer chemopreventive agents in vitro and in animal studies. However, the effects of green tea consumption in humans remain unclear. To investigate the associations between green tea consumption and all-cause and cause-specific mortality. The Ohsaki National Health Insurance Cohort Study, a population-based, prospective cohort study initiated in 1994 among 40,530 Japanese adults aged 40 to 79 years without history of stroke, coronary heart disease, or cancer at baseline. Participants were followed up for up to 11 years (1995-2005) for all-cause mortality and for up to 7 years (1995-2001) for cause-specific mortality. Mortality due to cardiovascular disease, cancer, and all causes. Over 11 years of follow-up (follow-up rate, 86.1%), 4209 participants died, and over 7 years of follow-up (follow-up rate, 89.6%), 892 participants died of cardiovascular disease and 1134 participants died of cancer. Green tea consumption was inversely associated with mortality due to all causes and due to cardiovascular disease. The inverse association with all-cause mortality was stronger in women (P = .03 for interaction with sex). In men, the multivariate hazard ratios of mortality due to all causes associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.93 (95% confidence interval [CI], 0.83-1.05) for 1 to 2 cups/d, 0.95 (95% CI, 0.85-1.06) for 3 to 4 cups/d, and 0.88 (95% CI, 0.79-0.98) for 5 or more cups/d, respectively (P = .03 for trend). The corresponding data for women were 1.00, 0.98 (95% CI, 0.84-1.15), 0.82 (95% CI, 0.70-0.95), and 0.77 (95% CI, 0.67-0.89), respectively (P<.001 for trend). The inverse association with cardiovascular disease mortality was stronger than that with all-cause mortality. This inverse association was also stronger in women (P = .08 for interaction with sex). In women, the multivariate hazard ratios of cardiovascular disease mortality across increasing green tea consumption categories were 1.00, 0.84 (95% CI, 0.63-1.12), 0.69 (95% CI, 0.52-0.93), and 0.69 (95% CI, 0.53-0.90), respectively (P = .004 for trend). Among the types of cardiovascular disease mortality, the strongest inverse association was observed for stroke mortality. In contrast, the hazard ratios of cancer mortality were not significantly different from 1.00 in all green tea categories compared with the lowest-consumption category. Green tea consumption is associated with reduced mortality due to all causes and due to cardiovascular disease but not with reduced mortality due to cancer.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                01 December 2017
                December 2017
                : 18
                : 12
                : 2586
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, The Centre of Postgraduate Medical Education, 00-416 Warsaw, Poland; czwo@ 123456op.pl (C.W.); as.jozwiak@ 123456op.pl (A.S.-J.); grzegorz.jakiel1@ 123456o2.pl (G.J.)
                [2 ]Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdansk, 80-210 Gdansk, Poland; luka@ 123456gumed.edu.pl
                [3 ]INVICTA Fertility and Reproductive Center, 80-172 Gdansk, Poland
                [4 ]Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-513 Poznan, Poland; blazejmeczekalski@ 123456yahoo.com
                [5 ]Students’ Scientific Association at the I Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland; mciebiera93@ 123456gmail.com
                Author notes
                [* ]Correspondence: michal.ciebiera@ 123456gmail.com ; Tel.: +48-607-155-177
                Author information
                https://orcid.org/0000-0001-5780-5983
                Article
                ijms-18-02586
                10.3390/ijms18122586
                5751189
                29194370
                e8bc9bc7-95b9-47c4-8778-2055adfc137d
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 October 2017
                : 28 November 2017
                Categories
                Review

                Molecular biology
                uterine fibroid,leiomyoma,vitamin d,paricalcitol,epigallocatechin gallate,elagolix,aromatase inhibitors,cabergoline,pharmacology

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