The Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Metabolic and Hormonal Disturbances in Polycystic Ovary Syndrome Patients

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among females of reproductive age. The main manifestations of this syndrome are ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. Noticeably, PCOS is associated with several metabolic disturbances such as insulin resistance, compensatory hyperinsulinemia, dyslipidemia and central obesity, which increase the risk for long-term complications like type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases. Moreover, previous data demonstrated that, compared to normo-ovulatory women, PCOS patients might exhibit a dysregulation in the IGF system represented as an elevation in the serum levels of free Insulin-like growth factor-1 (IGF-1) and a reduction in the serum levels of Insulin-like growth factor binding protein-1 (IGFBP-1). However, the exact aetiology of PCOS remains unclear and current treatments are only moderately effective at controlling PCOS symptoms and preventing its complications. Growing evidence suggests a role of vitamin D in female reproductive diseases as the expression of Vitamin D Receptors (VDR) was identified in many organs throughout the female reproductive tract. On the top of that, vitamin D regulates over 300 genes, including genes that are important for glucose and lipid metabolism. Moreover, vitamin D deficiency is a common condition among women with PCOS, and several studies indicated an association between low levels of serum 25-hydroxyvitamin D (25-OH-Vitamin D) and manifestations of PCOS including insulin resistance, hyperandrogenism, and infertility. Further, a recent in-vitro study showed that vitamin D regulated steroidogenesis and IGFBP-1 production in cultured human ovarian cells, and many reports have suggested an interrelation between IGF-1 and vitamin D.