The Role of Vitamin D in Polycystic Ovary Syndrome

1. GLUT4 Angela Bouska, Heather Knoll, Laura Shay Department of Food Science & Human Nutrition, Fall 2009 Abstract Sources of Vitamin D Application Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that results in cysts on the ovaries, high androgen levels, and anovulation. Vitamin D obtained through sun exposure, supplements or food is thought to alleviate androgenic symptoms of PCOS. In the proposed mechanism, vitamin D works to decrease androgenic effects by reducing parathyroid hormone (PTH) levels. PTH disrupts GLUT4, a glucose transport protein in adipose and muscle tissue. This results in insulin resistance and increased production of androgens. • Women with PCOS have a greater risk of developing insulin resistance. Over 50% of these women develop diabetes or pre-diabetes by the age of 40 (1). Daily sun exposure of the legs and arms for 20 minutes will provide a woman with adequate vitamin D. However, women in Northern latitudes may need to be exposed to the sun for longer amounts of time. During months of limited sun exposure, women should take a supplement or consume an adequate amount of vitamin D containing food sources (6). The vitamin D may aid in alleviating insulin resistance and androgenic symptoms of PCOS (4). The symptoms that may be alleviated include hirsutism, acne, anovulation, and central adiposity (1). Vitamin D may be obtained through sun exposure, supplements, and food. The recommended amount of vitamin D for a person age 19-50 years is 200-400 IUs (5-10 mcg). Research shows that up to 20 minutes in the sun per day is a good way to receive vitamin D. If taking a supplement, there are approximately 400 IUs in each multivitamin. Women with PCOS should be taking 800-1,200 IUs per day for several months to decrease symptoms of this syndrome. Foods containing high amounts of vitamin D are on the chart to the right (6). Objectives • To briefly explain the prevalence and background of PCOS. • To identify sources of Vitamin D. • To provide a literature review on the link between Vitamin D and PCOS. • To propose a mechanism of Vitamin D’s effect on PCOS. The Role of Vitamin D in Polycystic Ovary Syndrome Background Proposed Biochemistry of Vitamin D in PCOS Conclusion • PCOS is one of the most common endocrine disorders in females of childbearing age, affecting one in ten women of this age group. • Development of PCOS: • Follicles are small sacs in the ovaries that each contain one egg. Each month the follicles accumulate fluid, but only one of these grows large enough for the egg to mature. This follicle then breaks open to release the egg. However, in a woman with PCOS, not all of the hormones necessary for egg maturation are present. Several follicles accumulate fluid, but none of them grow large enough for the egg to mature. These follicles remain as ovarian cysts. • PCOS can impact a woman’s menstrual cycle, fertility, hormones, heart, blood vessels, and appearance. • The direct cause of PCOS is unknown. However, evidence shows that there are likely multiple contributing factors including a genetic factor, insulin resistance which leads to high androgen levels, and most recently vitamin D deficiency. • Although there is currently not a cure for PCOS, the symptoms of the disorder can be treated (1). Decreased GLUT4 protein expression PCOS is a common endocrine disorder in American women with an unknown etiology. Addition of vitamin D to the current treatment of PCOS could further aid in reducing insulin resistance, anovulation, and additional androgen induced symptoms of PCOS. Our research indicates that vitamin D may play a crucial role in the reversal of these symptoms. This has the potential to greatly impact the lives of women living with this disorder. Polycystic Ovarian Syndrome Increased Parathyroid hormone Vitamin D works to decrease PTH and ultimately reduce insulin resistance and androgenic symptoms of PCOS Insulin Resistance (50% of women with PCOS by the age of 40) 1,25 –Dihydroxyvitamin D Hyperinsulinemia Ovary Theca Cell Hyperplasia Anovulation References Increased Insulin-like growth factor Liver • United States. Department of Health and Human Services. Women's Health. Womenshealth.gov/Polycystic Ovary Syndrome (PCOS). U.S. Department of Health and Human Services, 1 Apr. 2007. Web. 05 Nov. 2009. <http://www.womenshealth.gov/faq/polycystic-ovary-syndrome.cfm>. • Rashidi, Batool, Fedieh Haghollahi, Mamak Shariat, and Farid Zayerii. "The Effects of Calcium-Vitamin D and Metformin on Polycystic Ovary Syndrome: A Pilot Study." Taiwan J Obstet Gynecol 48.2 (2009): 142-147. • Kotsa, Kalliopi, Maria P. Yavropoulou, Olympia Anastasiou, and John G. Yovos. "Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome." Fertility and Sterility 92.3 (2009): 1053-058. • Mahmoudi, Touraj. "Genetic variation in the vitamin D receptor and." Fertility and Sterility 4th ser. 92 (2009): 1381-1383. • Chang, Eugene, Shawn S. Donkin, and Dorothy Teegarden. "Parathyroid hormone suppresses insulin signaling in adipocytes." Molecular and Cellular Endocrinology 307 (2009): 77-82. • "Polycystic Ovary Syndrome (PCOS)." The Analyst. 13 Nov. 2009. Web. 14 Nov. 2009. <http://www.digitalnaturopath.com/cond/C485625.html>. • JP. "Mint Tea Warning." Healthy Fellow Your Natural Critic. 14 July 2009. Web. 5 Nov. 2009. <http://www.healthyfellow.com/290/mint-tea-warning/>. • "Biochemical and clinical features of PCOS." Endocrine and metabolic changes in women with polycystic ovaries and with polycystic ovary syndrome. Oulu University Library, 2000. Web. 3 Nov. 2009. <http://herkules.oulu.fi/isbn9514264266/html/x482.html>. • Wong, I. L. "Polycystic Ovary Syndrome (PCOS), Insulin Resistance (IR),." Hope IVF & Fertility Center. Web. 3 Nov. 2009. <http://www.hopeivf.com/resources/PCOS.IR.LWong.m.t.sj.pdf>. • Kajaia, Natia, Helge Binder, Ralf Dittrich, Patricia G. Oppelt, Bianca Flor, Susanne Cupisti, Matthias W. Beckmann, and Andreas Mueller. "Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome." European Journal of Endocrinology (2007): 499-507. EJE. 31 May 2007. Web. 02 Nov. 2009. <www.eje-online.org>. • Chang, Eugene. The effects of vitamin D on insulin sensitivity. Ph.D. dissertation, Purdue University, United States -- Indiana. Retrieved November 19, 2009, from Dissertations & Theses. • Galen, Donald I. "Polycystic Ovary Syndrome (PCOS)." Drgalen. Internet Health Resources, 2000. Web. 3 Nov. 2009. <http://www.drgalen.com/pcos.html>. Decreased Sex hormone binding globulin Decreased Insulin-like growth factor 1 binding protein Increased Luteinizing hormone (1) Increased androgen activity Literature Review • In a study of 60 women with PCOS, a combination of calcium-vitamin D and Metformin were more effective than calcium-vitamin D or Metformin alone at restoring normal menses and increasing follicular growth (2). • In a study of 15 obese women with PCOS who were either vitamin D deficient or insufficient, a vitamin D3 analogue supplement lowered serum PTH, lowered serum triglycerides, increased insulin sensitivity, increased insulin effectiveness, and increased serum HDL-cholesterol levels (3). • In a case-control study of 162 women with PCOS who were matched with 162 control women, vitamin D receptor genotypes were compared. Researchers found that a genetic variation in the receptor may affect the development of PCOS and insulin resistance in women with PCOS (4). • In a study of bovine cell cultures, researchers found that an increase in PTH reduced insulin-stimulated glucose uptake and decreased GLUT 4 and IRS-1 protein expression in differentiated adipocytes (5). Potentiates androgenic symptoms of PCOS (4,7,8,9,11,12) Insulin resistance and hyperinuslinemia are frequent metabolic abnormalities found in PCOS. The build-up of insulin is responsible for the excessive production of male hormones by the ovaries. The increased production of androgens causes male characteristics in women and leads to many of the signs and symptoms associated with PCOS (7). Insulin resistance is also linked to an increase in PTH in women with PCOS (8). This increase in PTH causes abnormal morphology in protein expression of the vitamin D receptor on GLUT4 in adipocytes. An increase in vitamin D is thought to decrease PTH, which appears to increase insulin sensitivity. The decreased insulin resistance does not promote excessive androgen production (5).