Is There An Association Between Vitamin D Levels And Insulin Resistance In Polycystic Ovary Syndrome?

Polycystic ovary syndrome (PCOS) is the most common gynecological endocrinopathy among women of reproductive age. The prevalence of PCOS among such women is estimated to be 6.4% to 6.8% worldwide. PCOS is a heterogeneous androgen excess disorder with different degrees of reproductive and metabolic dysfunctions.

There are many considerations to explain the complexity of the underlying pathogenesis of PCOS, particularly the well-known roles of hypothalamic-pituitary gonadal dysfunctions, metabolic abnormalities and genetic factors, the developmental model of chronic diseases postulates that early-life events affect the individual differences in vulnerability to lifestyle and environment, suggesting that hostile intrauterine environment and low birth weight may predispose to the development of early adrenarche, PCOS and metabolic syndrome later in life; however, the definite pathogenesis and real underlying etiologies of PCOS remain uncertain and ripe with opportunities for further research.

PCOS is the most common cause of anovulatory infertility, and its foremost clinical symptoms include anovulation or oligo-ovulation, infertility, menstrual irregularity, polycystic ovaries, and hyperandrogenism in women without specific underlying diseases of the adrenal or pituitary glands. A primary abnormality in folliculogenesis may have played a role in the development of PCOS. The polycystic ovaries contain multiple antral follicles, some of which prematurely acquire LH receptors and become responsive to LH, increasing granulosa cell proliferation in the preantral follicles, resulting in anovulation. PCOS is defined by the presence of having at least 2 of the following criteria: irregular or absent ovulation, elevated levels of androgenic hormones, and enlarged ovaries containing at least 12 follicles each.

Several epidemiological and interventional PCOS studies demonstrate that serum vitamin D concentrations are inversely associated with fasting plasma glucose levels, insulin resistance, body mass index (BMI), and body fat contributing to the pathogenesis of PCOS by promoting insulin resistance and affecting glucose metabolism in PCOS women. Vitamin D is either produced in the skin in response to direct exposure to sunlight from dehydrocholesterol or obtained from the diet. Vitamin D3 (cholecalciferol) is converted into 25-hydroxyvitamin D3 principally in the liver and 1,25-dihydroxyvitamin D3 in the kidney by two hydroxylation steps. 1,25-dihydroxyvitamin D3 is an active form of vitamin D, it binds to vitamin D receptors (VDRs) that are expressed in 2776 genomic positions and modulate the expression of 229 genes in more than 30 different tissues, such as the skeleton, pancreatic islet cells, parathyroid glands, and ovaries.

About 3% of the human genome are regulated by VDRs gene including those responsible for glucose and fat metabolism as well as blood regulation; it's active form acts through its VDRs either directly or through regulation of intercellular calcium that facilitates insulin secretion. It has been suggested that Vitamin D increases insulin sensitivity through the effect on its muscle cell receptors by increasing insulin receptors or increasing the insulin sensitivity of insulin receptors to insulin. Also, being a fat soluble vitamin, a higher proportion of vitamin D may be sequestered in the adipose tissue of obese individuals, resulting in lower 25-(OH)D3 concentration levels; therefore, a low vitamin D status is suspected to be a risk factor for impaired glucose tolerance, insulin resistance and a substantial cause of obesity.