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Review
. 2021 May 5;22(9):4905.
doi: 10.3390/ijms22094905.

A Narrative Review of Current Understanding of the Pathophysiology of Polycystic Ovary Syndrome: Focus on Plausible Relevance of Vitamin D

Rajeshwari Kalyanaraman  1 , Lubna Pal  2
Affiliations
Review

A Narrative Review of Current Understanding of the Pathophysiology of Polycystic Ovary Syndrome: Focus on Plausible Relevance of Vitamin D

Rajeshwari Kalyanaraman et al. Int J Mol Sci. .

Abstract

Polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy of reproductive years. Salient features in presentation of patients PCOS include menstrual dysfunction, hyperandrogenism and/or polycystic appearance of ovaries on ultrasound. While the diagnosis of PCOS depends on presence of specified criteria, misdiagnoses are common. Despite years of extensive research, the exact aetiology of PCOS remains largely unknown. In the past decade, apart from insulin resistance and hyperandrogenemia, anti-mullerian hormone (AMH), an important marker of ovarian reserve, and vascular endothelial growth factor (VEGF), a crucial factor in angiogenesis, have been examined as plausible players of causative relevance for PCOS. Vitamin D, a sex-steroid hormone that is universally known for its relevance for skeletal health, has received increasing attention due to growing evidence supporting its pivotal in reproductive physiology and in PCOS. In this review we summarize our current understanding of the mechanisms relevant to the pathophysiology of PCOS and examine the role of vitamin D signalling in this context.

Keywords: anti-mullerian hormone; polycystic ovarian syndrome; vascular endothelial growth factor; vitamin D.

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Conflict of interest statement

The authors report no conflict of interest.

Figures

Figure 1
Figure 1
Overview of vitamin D metabolism and salient reproductive and non-reproductive actions. Adapted from study by Luk et al. [52].
Figure 2
Figure 2
Vitamin D receptor (VDR) signalling and activation.
Figure 3
Figure 3
Parallel pathways demonstrating the role of Anti-mullerian hormone (AMH) in follicular development in normal (left) versus polycystic (right) ovaries. AMH is produced by the growing follicles and production ceases when the follicles reach a size ≥10 mm. AMH keeps FSH signalling in check. High levels of AMH in PCOS cause increased suppression of FSH signalling and result in (i) arrest in follicular growth, (ii) reduced activation of FSH mediated aromatase activation that contribute to increased androgen levels.
Figure 4
Figure 4
Effects of vitamin D supplementation on serum anti-mullerian hormone (AMH) levels differ by PCOS status: —effects seen in non-PCOS (a) and PCOS (b) populations. Adapted from Mordi et al. [73].
Figure 5
Figure 5
Schema outlining pathophysiology of polycystic ovarian syndrome (PCOS) related health burdens and targets for facilitatory effects of vitamin D (indicated by +).
Figure 6
Figure 6
Effect of vitamin D supplementation on vascular endothelial factor (VEGF) levels in comparison with placebo. Vit D supplementation was associated with significantly reduced serum VEGF levels in vitamin D deficient women with polycystic ovarian syndrome (PCOS). No significant changes were observed with placebo. Pre: Before vitamin D or placebo, Post: After vitamin D or placebo administration. Reprinted/Adopted from reference [110], with permission.
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