Prevalence of Musculoskeletal and Metabolic Disorders in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis.

Introduction: Musculoskeletal disorders could be associated with metabolic disorders that are common after kidney transplantation, which could reduce the quality of life of patients. The aim of this study was to assess the prevalence of both musculoskeletal and metabolic disorders in kidney transplant patients. Methods: MEDLINE, CINAHL, Cochrane Library, EMBASE and Web of Science were searched from their inception up to June 2023. DerSimonian and Laird random-effects method was used to calculate pooled prevalence estimates and their 95% confidence intervals (CIs). Results: 21,879 kidney transplant recipients from 38 studies were analysed. The overall proportion of kidney transplant patients with musculoskeletal disorders was 27.2% (95% CI: 18.4-36.0), with low muscle strength (64.5%; 95% CI: 43.1-81.3) being the most common disorder. Otherwise, the overall proportion of kidney transplant patients with metabolic disorders was 37.6% (95% CI: 21.9-53.2), with hypovitaminosis D (81.8%; 95% CI: 67.2-90.8) being the most prevalent disorder. Conclusion: The most common musculoskeletal disorders were low muscle strength, femoral osteopenia, and low muscle mass. Hypovitaminosis D, hyperparathyroidism, and hyperuricemia were also the most common metabolic disorders. These disorders could be associated with poorer quality of life in kidney transplant recipients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023449171].

Association of low vitamin D level and full-term early-onset neonatal sepsis; a case-control study.

BACKGROUND: Sepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country. METHODS: This case-control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture. RESULTS: Forty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml). CONCLUSION: In the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis).

Vitamin D deficiency and chronological hypoplasia with hypomineralisation: a case report.

Patients being reported for vitamin D deficiency (VDD) are increasing, particularly among the children and adolescents. This study aims to manifest the clinical and dental evaluations of a child with VDD, referred to the dental office. A 10-year-old British Asian boy was referred to the paediatric specialist dentistry clinic by the general dentist for dental management. The medical history depicted that the patient was diagnosed with VDD, secondary hyperparathyroidism and delayed growth. Moreover, his mother had the VDD during pregnancy. The patient was breast fed and had rickets in infancy. He was prescribed vitamin D supplements at the age of 16 months. He had received multiple dental treatments under local anaesthesia but with limited cooperation. Clinical examination revealed that the patient had chronological enamel hypoplasia shown as bands at the occlusal third on specific teeth. Suboptimal hygiene with general plaque induced gingivitis, dental caries in permanent and primary teeth, and delayed the teeth eruption. Preventions included appropriate oral hygiene and dietary advice, fluoride varnish application and fissure sealant placement. The treatments included anterior direct composite restoration, posterior composite restoration, stainless steel crowns and extractions. Thorough medical history is essential to understand the underlying causes of dental defects. Early dental intervention can restore the patient appearance and function and prevent further dental damage.

Frequency of vitamin D deficiency in children with iron deficiency anaemia and factors associated with vitamin D deficiency.

Objective: To evaluate vitamin D deficiency in children with iron-deficiency anaemia, and to identify the risk factors for such deficiency. METHODS: The cross-sectional study was conducted at the Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from October 2021 to March 2022, and comprised children aged 1-5 years who had been diagnosed with iron-deficiency anaemia. Quantitative variables, like age, height, weight, gender, socioeconomic status and sibling status, were controlled by stratification. Data was compared to assess the risk factors of vitamin D deficiency among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 236 children with iron-deficiency anaemia, 159(67.5%) also had vitamin D deficiency; 95(59%) girls and 65(41%) boys. Overall, 104(65.4%) subjects were aged 4-5 years and 55(34.6%) were aged 1-3 years. Vitamin D deficiency had significant association with female gender, older age, height and weight <5th centiles, educated parents, low to middle socioeconomic status, urban residence and higher number of siblings (p<0.05). CONCLUSIONS: The prevalence of vitamin D deficiency among children with iron-deficiency anaemia was found to be high.

Vitamin D and Menopause.

Menopause is the transition period in female life cycle. Resultant hormonal changes lead to adverse health effects. Women may seek treatment due to significant impairment in quality of life. Vitamin D deficiency is a globally prevalent problem. Vitamin D deficiency in menopausal women may aggravate the adverse health risks associated with menopause. In this article, the authors discuss endocrinology and clinical features of menopause, Vitamin D and its links with menopause, and the potential role of Vitamin D supplementation to combat detrimental multi-organ system effects of menopause.

Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition characterized by abnormal fat accumulation in the liver, often associated with metabolic disorders. Emerging evidence suggests a potential link between vitamin D deficiency and the development and progression of MASLD. The current review provides a concise overview of recent studies uncovering novel mechanistic insights into the interplay between vitamin D and MASLD. Several epidemiological studies have highlighted a significant association between low vitamin D levels and an increased risk of MASLD. Vitamin D, traditionally known for its role in bone health, has now been recognized as a key player in various physiological processes, including immune regulation and inflammation. Experimental studies using animal models have demonstrated that vitamin D deficiency exacerbates liver steatosis and inflammation, suggesting a potential protective role against MASLD. Mechanistically, vitamin D appears to modulate MASLD through multiple pathways. Firstly, the vitamin D receptor (VDR) is abundantly expressed in liver cells, indicating a direct regulatory role in hepatic function. Activation of the VDR has been shown to suppress hepatic lipid accumulation and inflammation, providing a mechanistic basis for the observed protective effects. Additionally, vitamin D influences insulin sensitivity, a critical factor in MASLD pathogenesis. Improved insulin sensitivity may mitigate the excessive accumulation of fat in the liver, thus attenuating MASLD progression. In parallel, vitamin D exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines implicated in MASLD pathophysiology. Experimental evidence suggests that the immunomodulatory effects of vitamin D extend to the liver, reducing inflammation and oxidative stress, key drivers of MASLD, and the likelihood of hepatocyte injury and fibrosis. Understanding the complex interplay between vitamin D and MASLD provides a basis for exploring targeted therapeutic strategies and preventive interventions. As vitamin D deficiency is a modifiable risk factor, addressing this nutritional concern may prove beneficial in mitigating the burden of MASLD and associated metabolic disorders.

Surgical Considerations for Osteoporosis, Osteopenia, and Vitamin D Deficiency in Upper Extremity Surgery.

Fragility fractures as a result of osteoporosis, osteopenia, or vitamin D deficiency are some of the most common injuries encountered in orthopedics and require careful consideration when determining the appropriate management and treatment options. A thorough perioperative evaluation can identify causes of low bone mineral density allowing for initiation of appropriate therapy. Surgical treatment of these fractures can be difficult, and techniques should be employed to ensure stable fixation. It is important to understand the potential pitfalls associated with treatment of fragility fractures to prevent avoidable complications. Postoperative management is key to preventing future injuries in this unique patient population.

Considerations Regarding Vitamin D in Foot and Ankle Treatment and Surgery.

Although the impact that vitamin D has on bone healing is uncertain in foot and ankle (F&A) surgery, there is support for vitamin D supplementation (2000 IU/day) with calcium (1 g/day) to promote bone healing. Although orthopedic F&A surgeons are frequently the first provider to detect the harbingers of osteoporosis by the occurrence of fragility fractures, this should trigger referral to the appropriate specialist for assessment and treatment. There is circumstantial evidence suggesting a role of hypovitaminosis D in bone marrow edema syndrome and possibly osteochondritis dissecans. There should be a low threshold for assessing vitamin D levels in such patients.

Comparative Study of Vitamin D Levels in Newly Diagnosed Tuberculosis and a Normal Population.

Background and Objectives: Tuberculosis (TB) is an ancient disease caused by Mycobacterium tuberculosis, a member of the Mycobacterium tuberculosis complex. It contributes to significant morbidity and mortality. Treatment of TB poses a considerable challenge because of emerging drug resistance and the longer duration of therapy. Various past studies, both in vitro and in vivo, have established the role of vitamin D in the pathogenesis and treatment of TB. Results of in vivo studies are inconsistent, and this study aims to determine vitamin D levels and their association with newly diagnosed TB (pulmonary and extrapulmonary) cases and normal populations. Material and Methods: A Prospective Case-Control study with 116 subjects (58 cases and 58 controls) was conducted over two years. 29 cases of pulmonary TB and 29 cases of extrapulmonary TB constituted 58 cases of TB. Vitamin D levels were measured and compared in both the cases and controls. Data analysis was carried out using SPSS software 22.0. Results: The prevalence of vitamin D deficiency was 68.96% in the cases, while it was 51.72% in the controls. The reported median and quartile of serum vitamin D levels were 14.35 ng/mL (8.65, 25.48) in the TB group and 19.08 ng/mL (13.92, 26.17) in the control group. There was a significant statistical difference between the TB and non-TB populations with a p-value of 0.029 on the Mann-Whitney test. Conclusion: Vitamin D deficiency was more prevalent in individuals with TB than those without TB.

The Relationship between Frontal QRS-T Angle and Vitamin D Deficiency.

Background and Objectives: A deficiency in serum 25-hydroxyvitamin D levels is associated with a number of cardiovascular situations, such as high blood pressure, heart failure, atherosclerotic heart disease, and peripheral artery disease. The frontal QRS-T angle has recently been proposed as a marker of ventricular repolarization. A wider frontal QRS-T angle has been positively correlated with adverse cardiac events. The objective of our study was to examine the association between serum 25-hydroxyvitamin D level and the frontal QRS-T angle. Materials and Methods: A total of 173 consecutive patients aged 18-60 years undergoing routine cardiology check-up evaluation, and not receiving concurrent vitamin D treatment were included in the study. Patients were classified in three groups, depending on their vitamin D levels, and categorized as follows: Group 1-deficient (<20 ng/mL), Group 2-insufficient (20-29 ng/mL), or Group 3-optimal (≥30 ng/mL). The frontal QRS-T angle was determined using the automated reports generated by the electrocardiography machine. Results: The average age of participants was 45.8 (±12.2) years, and 55.5% of participants were female (p < 0.001). Individuals with low vitamin D concentrations exhibited a wider frontal QRS-T angle. It was determined that vitamin D level is an independent predictive factor for the frontal QRS-T angle. Conclusions: As the levels of 25-hydroxyvitamin D decrease, repolarization time assessed by frontal QRS-T angle is widened. Our findings indicate that lower concentrations of vitamin D may increase the susceptibility to ventricular arrhythmia.

Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis.

Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels and maintaining bone health. However, it was later discovered that many organs express vitamin D metabolizing enzymes and have a ligand for vitamin D, which regulates the expression of an extensive assortment of genes. As a result, vitamin D is indispensable for the proper function of organs, and its deficiency is believed to be a critical factor in symptoms and disorders such as cardiovascular diseases, autoimmune diseases, and cancers. The significance of vitamin D in reproductive tissues was recognized later, and studies have revealed its crucial role in male and female fertility, as well as proper reproductive function during pregnancy. Vitamin D deficiency has been identified as a risk factor for infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, and endometriosis. However, data investigating the association between vitamin D levels and reproductive disorders, including endometriosis, have encountered inconsistencies. Therefore, the present study aims to review existing research on the effect of vitamin D on proper reproductive function, and the role of deficiency in reproductive diseases and specifically focuses on endometriosis.

The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance.

Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body's homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.

Implications of maternal vitamin D administration for the neonatal respiratory distress syndrome: A randomized clinical trial.

BACKGROUND: Vitamin D deficiency has been suggested to be a risk factor for neonatal respiratory distress syndrome (RDS). This study aimed to evaluate the effect of 25 (OH) D administrations in pregnant women with findings of preterm labor on the incidence of RDS in their preterm neonates. MATERIALS AND METHODS: A randomized controlled clinical trial was conducted on pregnant mothers with gestational age (GA) of less than 34 weeks at risk of preterm delivery. 175 subjects were randomly assigned into two groups, including intervention (intramuscular injection of 50,000 units of 25(OH) D during 72 hours before delivery) and control (no injections). Serum concentrations of 25(OH) D were measured shortly after birth in both mothers and neonates. Then, clinical and laboratory results of mothers and their offspring were recorded (in a checklist). Short-term outcomes and the need for respiratory support were also assessed. Data were analyzed by independent t-test, Mann-Whitney U test, Fisher's exact test, and chi-square test. RESULTS: Even though gestational age, birth weight, delivery method, and serum vitamin D levels are consistent among both groups, 45% of neonates in the control group and 20% in the intervention group developed respiratory distress syndrome (P = 0.05). The mean 25(OH) D level in neonates was 17.7±10.5 and 19.29±9.94 ng/mL in the intervention and control groups, respectively (P > 0.05). CONCLUSION: A single dose of 50,000 units of intramuscular 25(OH)D in pregnant women at risk of preterm labor can lower the risk of RDS in the infant.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Association between serum 25-hydroxyvitamin D3 level and cognitive impairment in older chronic kidney disease patients.

This study aims to examine whether hypovitaminosis D was associated with cognitive impairment among chronic kidney patients with different level of albuminuria. This population-based cross-sectional study was conducted on elderly (over 60 years old) with urine albumin to creatinine ratio (UACR) ≥ 30 mg/g from 2011 to 2014 in the US National Health and Nutrition Examination Survey (NHANES). Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning (CERAD). Subjects were divided into 2 groups according to the absence or presence of cognitive impairment and a propensity score matching (PSM) was further conducted. The association was assessed with Spearman correlation and logistic regression analysis. The positive association of 25-hydroxyvitamin D3 (25(OH)D3) and cognitive score was presented. PSM analysis revealed that a higher level of 25(OH)D3 correlated to a better cognitive function in CKD patients with albuminuria, especially in patients with 30 mg/g ≤ UACR < 300 mg/g. This study indicated that a low 25(OH)D3 level was associated with poor cognitive performance, especially in patients with microalbuminuria. Thus, early diagnosis of vitamin D insufficiency and an effective intervention might be a useful therapeutic strategy to prevent cognitive decline in patients with the progression of renal dysfunction.

Interplay between vitamin D status, vitamin D receptor gene variants and preeclampsia risk in Ghanaian women: A case-control study.

BACKGROUND AND AIM: Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2-8% of pregnancies worldwide, with detrimental consequences for both mother and foetus. Evidence, suggests that genetic factors, including vitamin D receptor (VDR) gene polymorphisms, could contribute to PE complexity. However, their role in the Ghanaian population remains underexplored. We assessed the interplay between Vitamin D, VDR gene variants and preeclampsia risk in Ghanaian women. METHODS: This unmatched case-control study was conducted at Kumasi South Hospital, Ghana, from June to November 2022. A total of 162 participants consisting of 62 PE cases and 100 normotensive controls were enrolled. Clinical and obstetric data were collected. Blood samples were also collected for DNA extraction and vitamin D assay. Genotyping of VDR Fok1 and Bsm1 gene variants was performed using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis whereas Vitamin D levels were estimated using sandwich ELISA. Statistical analyses were computed with SPSS version 25 and GraphPad prism version 8.0. A p-value of < 0.05 was considered statistically significant. RESULTS: Vitamin D concentration were significantly lower in the PE group (p < 0.0001). Vitamin D deficiency (aOR = 3.311, 95% CI: 1.584-6.921, p = 0.0010) was significantly associated with a three-fold increase in preeclampsia risk, whilst VDR gene variants, particularly the "bb" genotype (cOR = 0.227, 95% CI: 0.055-0.944, p = 0.0410) was associated with reduced risk of PE. There was no association between the distribution of Fok1 genotypes and PE. CONCLUSION: This study highlights a significant association between vitamin D deficiency and an increased risk of PE among Ghanaian women. However, the VDR gene variant, "bb", genotype, for Bsm1 reduces the risk of PE.

Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study.

BACKGROUND: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS: We 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, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.