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      Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial

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          Abstract

          Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect −0.335, 95% CI −0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

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          Most cited references39

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          Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)

          (2004)
          Since the 1990 NIH-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include: menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
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            Polycystic ovary syndrome: etiology, pathogenesis and diagnosis.

            Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, with a prevalence of up to 10%. Various diagnostic criteria have been proposed, generally centered around the features of hyperandrogenism and/or hyperandrogenemia, oligo-ovulation and polycystic ovarian morphology. Insulin resistance is present in a majority of cases, with compensatory hyperinsulinemia contributing to hyperandrogenism via stimulation of ovarian androgen secretion and inhibition of hepatic sex hormone-binding globulin production. Adipose tissue dysfunction has been implicated as a contributor to the insulin resistance observed in PCOS. Environmental and genetic factors also have a role in the development of PCOS. The syndrome is associated with numerous morbidities, including infertility, obstetrical complications, type 2 diabetes mellitus, cardiovascular disease, and mood and eating disorders. Despite these morbidities, PCOS may be common in our society owing to evolutionary advantages of the syndrome in ancient times, including smaller family sizes, reduced exposure to childbirth-related mortality, increased muscle mass and greater capacity to store energy. The diagnosis of PCOS hinges on establishing key features while ruling out other hyperandrogenic or oligo-ovulatory disorders. Treatment is focused on the goals of ameliorating hyperandrogenic symptoms, inducing ovulation and preventing cardiometabolic complications. © 2011 Macmillan Publishers Limited. All rights reserved
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              Polycystic ovary syndrome.

              Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects about one in 15 women worldwide. The major endocrine disruption is excessive androgen secretion or activity, and a large proportion of women also have abnormal insulin activity. Many body systems are affected in polycystic ovary syndrome, resulting in several health complications, including menstrual dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome. Women with this disorder have an established increased risk of developing type 2 diabetes and a still debated increased risk of cardiovascular disease. The diagnostic traits of polycystic ovary syndrome are hyperandrogenism, chronic anovulation, and polycystic ovaries, after exclusion of other conditions that cause these same features. A conclusive definition of the disorder and the importance of the three diagnostic criteria relative to each other remain controversial. The cause of polycystic ovary syndrome is unknown, but studies suggest a strong genetic component that is affected by gestational environment, lifestyle factors, or both.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                07 February 2021
                February 2021
                : 13
                : 2
                : 547
                Affiliations
                [1 ]Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; verena.schwetz@ 123456medunigraz.at (V.T.-S.); stefan.pilz@ 123456medunigraz.at (S.P.); barbara.obermayer@ 123456medunigraz.at (B.O.-P.); christian.trummer@ 123456medunigraz.at (C.T.)
                [2 ]Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria; martina.kollmann@ 123456medunigraz.at (M.K.); monika.woelfler@ 123456medunigraz.at (M.W.)
                Author notes
                [* ]Correspondence: elisabeth.lerchbaum@ 123456medunigraz.at ; Tel.: +43-316-385-82383
                Author information
                https://orcid.org/0000-0001-8528-4759
                Article
                nutrients-13-00547
                10.3390/nu13020547
                7914670
                33562394
                25ec9169-b5ca-451f-9bdc-c1bb16512d42
                © 2021 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
                : 21 December 2020
                : 02 February 2021
                Categories
                Article

                Nutrition & Dietetics
                vitamin d,polycystic ovary syndrome,anti-müllerian hormone,follicle-stimulating hormone,randomized controlled trial

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