Vitamin D for the Treatment of Women With Polycystic Ovary Syndrome (PCOS)

The purpose of this study is to determine if vitamin D will improve insulin resistance, inflammation, and overall well-being in women with PCOS.

As many cells throughout the body possess the vitamin D receptor, adequate vitamin D levels may be essential for multiple physiologic functions. In recent years, vitamin D insufficiency has been linked to insulin resistance, inflammation, poor psychological health, obesity, type 2 diabetes, and cardiovascular disease - these are also commonly found in women with Polycystic Ovary syndrome (PCOS). We believe that vitamin D insufficiency contributes to insulin resistance, inflammation, and psychological distress in women with PCOS. These adverse effects may ultimately increase the risk for serious long-term complications in PCOS, including type 2 diabetes and cardiovascular disease. The key objectives of this research study are to determine the effects of vitamin D supplementation on insulin resistance, inflammation, mood and overall well-being in women with PCOS. The protocol has been modified by adding the following specific aim: To compare vascular function in healthy age and BMI similar matched women to PCOS women pre-treatment. Our hypothesis is that PCOS women will have greater attenuations in retinal vascular reactivity compared to healthy control women, demonstrating poorer endothelial function. We are currently recruiting healthy women who are age and BMI similar to the PCOS women and measure their retinal vascular reactivity for comparisons to the PCOS women's pre-treatment vascular reactivity. These healthy women will only have a baseline visit in which retinal vascular reactivity will be measured. They will not be enrolled in the placebo or Vitamin D randomization process as described above.

Quantitative insulin sensitivity check index (QUICKI) is a validated measure of insulin sensitivity based on fasting insulin and glucose. Quantitative insulin sensitivity check index (QUICKI) = 1/[log(I(0)) + log(G(0))]).

Participants underwent a 75-gram oral glucose tolerance test, in which blood samples for glucose and insulin were obtained at 0 and 2 hours and used to calculate the insulin sensitivity index (ISI 0,120).

Participants underwent a 75-gram oral glucose tolerance test, in which blood samples for glucose and insulin were obtained at 0 and 2 hours and used to calculate the insulin sensitivity index (ISI 0,120).

Participants underwent a 75-g oral glucose tolerance test, in which blood samples for glucose and insulin were obtained at 0 and 120 minutes and used to calculate the insulin sensitivity index (ISI0,120). The ISI 0,120 = the glucose uptake rate divided by the mean plasma glucose divided by the log(mean serum insulin).

Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is a validated measure of insulin resistance based on fasting insulin and glucose. HOMA-IR is calculated as the product of fasting glucose and insulin divided by 22.5.

Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.

Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.

Vitamin D binding protein levels were assessed as it has been linked with insulin resistance and type 2 diabetes.

Intact parathyroid hormone levels were assessed as they have been linked with obesity and insulin resistance.

Inclusion Criteria: Diagnosis of PCOS based on: Eight or fewer menstrual periods per year or spontaneous intermenstrual periods of greater than or equal to 45 days, and Elevated testosterone levels Exclusion Criteria: Current Pregnancy or Nursing Elevated calcium Kidney Stones or kidney disease Current use of vitamin D (other than a multivitamin) Use of metformin or other insulin sensitizing drugs in the last 3 months Elevated prolactin or untreated thyroid disease Diabetes, Liver disease, Heart disease, or other serious medical condition

Raja-Khan N, Shah J, Stetter CM, Lott ME, Kunselman AR, Dodson WC, Legro RS. High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial. Fertil Steril. 2014 Jun;101(6):1740-6. doi: 10.1016/j.fertnstert.2014.02.021. Epub 2014 Mar 14.