Although the exact cause and pathogenesis of PCOS have yet to be fully understood, active research has focused on the connection between deficient vitamin D status and PCOS, both in its development and in the increase of its metabolic and hormonal abnormalities [8–10]. Our study explored the link between vitamin D deficiency and PCOS among Saudi women, with results demonstrating impaired metabolic and hormonal activity, as evidenced by IR, hyperinsulinemia, excess LDL-C, TGs, LH and testosterone levels in this population. The PCOS group also had significantly lower amounts of serum 25(OH)D than did the group without PCOS.
Among the most widespread nutritional health problems globally, Vitamin D deficiency affects between 20 and 48% of the general adult population [10], a prevalence that rises to between 58 and 91% of women experiencing subfertility [16]. There is some disagreement on the ideal amount of 25(OH)D, but 20 ng/ml can be thought of as indicative of vitamin D sufficiency [15]. In our study, 41% of healthy women and 95% of women with PCOS had 25(OH)D concentrations of less than 20ng/ml.
In Saudi Arabia, as in other nations of the Middle East, vitamin D deficiency has been recorded in the population at large, but the extent of this deficiency in premenopausal women warrants more research. Data from previous observational studies on vitamin D status in women with PCOS have been inconsistent [16, 17]. One study found that vitamin D treatment results in improvement of menstrual frequency in PCOS women affected by menstrual disturbances [18]. A large cross-sectional study comparing women with PCOS and fertile controls found that the PCOS cases had reduced serum vitamin D concentrations compared to their healthy peers [19]. Likewise, in the present study, we found reduced serum 25(OH)D concentrations in Saudi women with PCOS in comparison with their healthy peers, and the extent of deficiency (25(OH)D < 12ng/ml) was even greater in this group than in the controls.
Part of exploring the mechanisms underlying the probable vitamin D-PCOS link must include how vitamin D acts to regulate insulin signaling and sensitivity, in addition to the expression of vitamin D receptors in classic and non-classic insulin-sensitive tissues [8, 9, 20]. Research should also investigate the key role of vitamin D in predicting IR in cases of PCOS [21]. The clinical hallmarks of PCOS are closely linked to those of metabolic syndrome, including abnormalities in glucose metabolism and IR [22]. A metareview of 35 studies found that approximately one-third of women with PCOS exhibited IR and compensatory hyperinsulinemia, which would progress to type 2 diabetes mellitus in about 10% [23]. In our analyses, serum 25(OH)D values in PCOS cases were negatively associated with markers of IR. These findings add to evidence suggesting that vitamin D deficiency contributes to the prevalence of PCOS and its associated metabolic complications [8, 9, 20] and underscore the pressing need for vitamin D monitoring in PCOS patients [20].
One way that vitamin D may positively impact insulin action is by improving insulin responsiveness for glucose transport through an increase in insulin receptor expression [24]. Vitamin D is also involved in the regulating extracellular and intracellular calcium, a key component of insulin-mediated intracellular processes in insulin-sensitive tissues like skeletal muscle and adipose tissue [24]. Further, as vitamin D moderates the immune system, vitamin D deficiency may trigger an increased inflammatory response, which is associated with IR [25]. A final mechanism may be linked to impaired β-cell function observed in women with PCOS. Considered collectively, these findings may at least partially explain the correlations linking serum 25(OH)D concentrations in PCOS patients to their IR markers. Additional support of this link can be found in reports of improved insulin sensitivity in vitamin D-deficient PCOS cases after they were given vitamin D-based treatment [12, 13].
Another difference reported between women with PCOS and those without lies in their lipid parameters. Women with PCOS were reported as more likely to exhibit dyslipidemia, as evidenced by elevated TGs and LDL, and lower HDL [26]. Similarly, in the current study, higher LDL and TGs values were observed in patients with PCOS. More importantly, our study established a significant negative association between serum 25(OH)D values and levels of LDL and TGs in women with PCOS. Growing evidence points to the connection linking vitamin D status to metabolic health [8, 17, 19]. Given the connection between markers of dyslipidemia and cardiovascular disease, vitamin D supplementation may improve blood lipid levels and thereby lower the rate of cardiovascular abnormalities in women with PCOS who have vitamin D deficiency.
One of the clinical manifestations of PCOS is obesity, which has also been associated with hypovitaminosis D [27]. Our results of a significant and negative relationship between BMI and serum 25(OH)D values in PCOS cases support those of previous research [8, 28]. While the connection of Vitamin D deficiency to obesity is established, what is less clear is whether hypovitaminosis D is a cause or a consequence of obesity. It may be that vitamin D is sequestered in body fat, leading to lower amounts of serum vitamin D in the obese. Another theory is that the obese may have less exposure to sunlight, a necessary component for vitamin D synthesis in the skin. This explanation may make sense for women with PCOS, who are more likely to avoid going out in public because of changes in their appearance.
Further research also supports the connection between vitamin D replacement therapy and the improvement of subfertility and metabolic imbalance. A recent study on both obese and lean women with PCOS focused on explaining this connection by showing that vitamin D administration lowered levels of the key inflammatory marker, serum NF-kβ [29]. Another study found that in obese women with PCOS, vitamin D replacement therapy significantly reduced HOMA-IR values [30]. All this research suggests that vitamin D supplementation warrants consideration as one of the components considered in the treatment of PCOS.
Several limitations of the current study must be considered in the interpretation of the findings. This study focused on a single center, and the sample size was relatively small. Another limitation is that this was a cross-sectional study, making it impossible to confirm any temporal causal relationship between vitamin D and PCOS. Furthermore, physical activity, vitamin D dietary intake, variations of seasonal effect on vitamin D, and duration of daily sun exposure were not taken into account, which might confound the results showing a link between vitamin D and metabolic parameters. However, although we used a single measurement of vitamin D and did not take seasonal change in vitamin D into account, there is plenty of sunshine yearlong in Saudi Arabia, making the seasonal factor less pertinent than in other populations. To bolster the implications of these findings, this research needs to be conducted in multiple centers with a large sample size in other areas in Saudi Arabia. Nevertheless, this was one of a limited number of studies assessing how vitamin D deficiency correlates with metabolic and endocrine disorders in Saudi PCOS subjects in our country, and the study results may serve as the basis for a future larger controlled trial.