New Study Reveals Causal Link Between Low Vitamin D Levels and Polycystic Ovary Syndrome
China: In a groundbreaking development, a recent bidirectional Mendelian randomization study has uncovered a compelling causal association between low vitamin D levels and polycystic ovary syndrome (PCOS) incidence. This finding sheds new light on the intricate interplay between hormonal imbalances and nutritional factors in the development of this common endocrine disorder affecting women of reproductive age.
The findings, published in the Journal of Ovarian Research revealed that genetically predicted lower serum vitamin D (VD) levels may cause a higher risk of developing PCOS, which may be mediated by increased production of testosterone.
PCOS is characterized by a combination of symptoms, including irregular menstrual cycles, excess androgen levels, and ovarian cysts. While its exact etiology remains elusive, previous research has implicated genetic predispositions and environmental influences. Among these factors, vitamin D deficiency has long been suspected to play a role, given its regulatory functions in reproductive health and immune system modulation.
Bingrui Gao, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P.R. China, and colleagues aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms.
For this purpose, the research team assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis.
Subsequently, they conducted an MR mediation analysis to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, they integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and potentially related genes were used for functional enrichment analysis to evaluate the involvement of testosterone and the potential mechanisms.
Based on the study, the researchers reported the following findings:
• TS-MR analysis showed that individuals with lower serum VD levels were more likely to develop PCOS (OR = 0.750).
• MR mediation analysis uncovered an indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983).
• Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process.
“Our studies confirmed the causality between lower serum vitamin D level and higher PCOS risk,” the researchers wrote. “Furthermore, testosterone may act as a mediator between serum VD and PCOS.”
“These findings emphasize the clinical importance of testing serum vitamin D level and timely VD supplementation as possible primary prevention and treatment of PCOS,” they concluded.
Reference:
Gao, Bingrui, et al. “Causal Association Between Low Vitamin D and Polycystic Ovary Syndrome: a Bidirectional Mendelian Randomization Study.” Journal of Ovarian Research, vol. 17, no. 1, 2024, p. 95.
