As a matter of fact, PCOS is the most common ovarian disorder that affects 6–10% women worldwide  and accounts for 70% of cases of anovulatory infertility. PCOS is a set of reproductive and metabolic symptoms associated with an imbalance of reproductive hormones in women .
The pandemic of VD deficiency represents a major public health concern, as this disorder is associated with an increased risk of medical comorbidities contributing to a significant rise in mortality. There are intriguing reports suggesting that VD deficiency is more prevalent among women with PCOS . Few studies explored the association between VD deficiency with hirsutism score, IR, and obesity in PCOS . Because the current treatment of PCOS is still suboptimal, and cardio-metabolic diseases are the common cause of death all over the world, we aimed in the present study to investigate the levels of 25(OH)-D in PCOS patients. We also aimed to clarify the impact of vitamin D supplementation cardio-metabolic status, androgen profile, and clinical features of PCOS.
In order to assess the risk of cardiovascular disease among PCOS, our results revealed that the cardio-metabolic factors; systolic blood pressure, TC, TG, LDL cholesterol, FPG, 2-h plasma glucose, FSI, HOMA-IR, and CIMT were significantly high in PCOS compared to control group. Our previous experience also suggested that PCOS women had higher values of parameters of hyperglycemia and dyslipidemia as well as obesity indices [20,21,22].
Our findings are in concordance with Glueck et al. who found that PCOS patients are at an increased risk of metabolic syndrome and cardiovascular risk factors in later life .
Supporting our results, Zhao et al. detected a high risk of coronary heart disease in PCOS . Moreover, Morgan et al. study detected higher mortality in PCOS compared to the control group .
Regarding lipid profile in PCOS women, similar to our results Wild et al. showed that women with PCOS have higher levels of TG, LDL cholesterol, and TC, and lower HDL cholesterol levels compared with the control group . In addition, Mulhim et al. conducted their study to assess the metabolic and clinical profile of Saudi patients with PCOS, they found that PCOS patients had non- significantly difference in TC, HDL cholesterol, TG, LDL cholesterol, or FPG values compared to control group .
In order to better elucidate the levels of inflammatory markers in PCOS. In our research, we found significant higher levels of inflammatory markers; WBC, neutrophil as well as hs-CRP in PCOS cases compared to controls.
Similar to these results, our previous finding showed that PCOS patients had significant higher values of inflammatory biomarkers including serum procalcitonin, hs-CRP, WBC, and neutrophil counts compared to healthy women [20,21,22]. Altogether, these data point to VD acts to lower systemic inflammation in general by interacting with transcription and expression of cytokine genes [28,29,30].
Omics studies have indeed demonstrated that VD could under-regulate the activation of nuclear factor-κB , which plays a regulatory role for pro-inflammatory cytokine generation associated with the resistance of insulin [31, 32].
We in this study attempted to explore the levels of serum 25(OH)-D in PCOS, we found significant lower levels of serum 25(OH)-D in PCOS women compared with healthy controls. Even more importantly, our results reported that 25(OH)-D levels were negatively correlated with cardio-metabolic risk including, systolic blood pressure, serum triglycerides, HOMA-IR, FSI, BMI, CIMT, free testosterone, AFC, ovarian volume, and hs-CRP.
Our findings are in concordance with Wehr et al. hypovitaminosis D which was common in PCOS women . Similar results were described in Hahn et al. study which was conducted on women with PCOS, and they found lower levels of serum 25(OH)-D in PCOS women .
In that context, a study conducted by Jia et al. observed that the serum concentration of vitamin D is associated with the risk of PCOS. Nonetheless, they did not observe any improvement of clinical and laboratory features after vitamin D3 supplementation for women with PCOS .
In contrast, a study by Panidis et al.  found no significant difference of serum 25(OH)-D concentrations between women with PCOS and controls.
Supporting our results, Li et al. found that metabolic risk factors were associated with lower levels of serum 25(OH)-D in PCOS women . Additionally, Wehr et al.  observed that the serum 25OH-D level is positively correlated with insulin sensitivity and negatively correlated with IR in women with PCOS.
In earlier published studies conducted in our region, Middle East , Zhang et al. observed low VD in diabetes and the possible mechanisms for this association may include the presence of vitamin D receptors in pancreatic beta cells to which circulating vitamin D binds . In addition, VD has been well recognized for its role in regulating extracellular calcium flux, and insulin secretion is known as a calcium-dependent process .
Similar to our results, some studies report inverse associations between serum 25(OH)-D levels and testosterone among women with PCOS [33, 41,42,43].
Our finding adds to the growing body of evidence implicating that women with PCOS tend to have decreased vitamin D levels, and vitamin D deficiency has been correlated with increased IR, BMI, total testosterone, and DHEA-S .
There is scattered evidence for the role of VD treatment in improving various clinical parameters in vitamin D-deficient women with PCOS including glucose intolerance, hypertension, and androgen levels [43, 44].
The main finding in the current study explored the impact of VD supplementations (42,000 IU oral vitamin D per week and 500 mg calcium carbonate per day for 12 weeks) on serum lipids and glucose parameters.
The current study revealed that in the PCOS group, after VD supplementation, there were significant improvements of glycemic parameters including FPG, FSI, HOMA β, and HOMA-IR, compared to PCOS women at baseline of the study as well as an improvement of obesity indices BMI and WHR.
Similar results observed by Pal et al. found that VD supplementation has been shown to improve blood pressure and decrease IR, total testosterone, and androstenedione levels in vitamin D-deficient women with PCOS .
Supporting our results, in a study by Wehr et al., PCOS women receiving weekly 20,000 IU of vitamin D3 for 24 weeks demonstrated a significant decrease in triglycerides at 12 weeks and 24 weeks .
Our findings are in concordance with Kotsa et al. showed that triglyceride level significantly decreased and HDL significantly increased in 15 obese women with PCOS after they received alfacalcidol 1 g/d for 3 months .
Regarding the PCOS phenotype, androgenic profile, and inflammatory markers, there were significantly decreased values after the intervention. Even more important, 25(OH)-D serum levels were increased after VD supplementations.
Interestingly, Yildizhan et al. found that the administration of high doses of vitamin D led to the attenuation of hyperandrogenism and menstrual disturbances in women with PCOS. Moreover, treatment of low concentrations of 25(OH)-D should be kept in mind during managing obese women with PCOS .
Similar results were described in Selimoglu et al. study conducted on PCOS patients vitamin D supplementation has been shown to improve cardio-metabolic risks and androgenic profile in vitamin D-deficient women with PCOS .
Against our results, Pal and colleagues demonstrated that 3 months of daily oral supplementation of vitamin D (8533 IU) and calcium (530 mg) did not influence IR .
Furthermore, regarding the lipid profile, we observed that supplementation with VD had significant effects on the lipid profile.
In our research, we investigated PCOS women for assessment and the influence of VD supplementation on inflammatory biomarkers; in hs-CRP and neutrophil count, there was a highly significant decrease of inflammatory biomarker Moreover, logistic regression analysis was performed to detect predictors associated with VD supplementation among PCOS cases. Of note, logistic regression analysis revealed that among clinical and laboratory features of women with PCOS, androstenedione, FSI, and Hirsutism score were independent predictors of response to VD supplementation.
The only dropout of our study was that not all the enrolled patients in our study complete the trial as the final total number of women enrolled in this study was 55 patients of the intervention group and 40 PCOS patients of the non-intervention group. Thus, we excluded all subjects who did not complete this study. Of note, there were no adverse effects of VD supplementation during the intervention.