Associations between serum vitamin D and the risk of female reproductive tumors: A meta-analysis with trial sequential analysis

Abstract

Background: Female reproductive tumors are common with high morbidity and mortality worldwide; however, the association between gynecological tumors and serum vitamin D is controversial. The aim of this meta-analysis was to evaluate the relationship between insufficiency of serum vitamin D and the occurrence of benign and malignant gynecological tumors.

Methods: Studies from inception to June 2017 were searched in the electronic databases: National Library of Medicine (PubMed), Web of Science (Clerivate), and Cochrane Database of Systematic Reviews (Cochrane Library, CDSR) by 2 investigators independently. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. STATA 12.0 Software and Trial Sequential Analysis (TSA) software were applied for data analyses.

Results: Overall, 8 studies (including 2391 patients and 5798 patients with and without female reproductive tumors, respectively) were eligible for the present meta-analysis. In the subsequent meta-analysis, the occurrence of vitamin D deficiency in the case and control groups were 52.36% and 48.70%, respectively; women with female reproductive benign and malignant tumors were 55.57% and 50.59%, respectively. Although, no conclusive association was found between vitamin D deficiency and female reproductive tumors (OR, 1.05; 95% CI, 0.85-1.31); vitamin D deficiency may be a risk factor of malignant female reproductive neoplasm, as shown by the pooled OR (95% CI):1.17 (1.02-1.33). Furthermore, based on the OR values, association of vitamin D insufficiency with disease type, study location, number of patients, and methods for detecting CLA was observed. Similar results in the sensitivity analysis were observed. TSA showed that the cumulative Z-curve crossed the traditional boundary line, rather than crossing the trial sequential monitoring boundary. However, the cumulative information failed to reach the required information size.

Conclusions: Currently, vitamin D deficiency appears to be a common issue in females, and there may be an urgent need to improve the level of vitamin D. Furthermore, vitamin D deficiency may be a non-negligible risk factor of malignant female reproductive neoplasm. Undoubtedly, more trials are required in the future according to TSA.

Figure 1

The flow diagram of studies selection.

Figure 2

Forest plot shows the relation between vitamin D and female reproductive tumors.

Figure 3

Sensitivity analysis about serum vitamin D insufficient of benign and malignant lesions in female reproductive system. The study of Mitro et al and Zheng et al may be the origin of heterogeneity. The detailed data was shown in supplement table.

Figure 4

The funnel plot about serum vitamin D of benign and malignant lesions in female reproductive system.

Figure 5

Trial sequential analysis (TSA) about serum vitamin D insufficient of benign and malignant lesions in female reproductive system. The solid blue line is the cumulative Z-curve. To the left, the red, inward-sloping, solid lines make up the trial sequential monitoring boundaries. To the right, the vertical red line represents required information size (RIS) of this meta-analysis. The black dashed lines represent the conventional statistical boundaries. TSA = trial sequential analysis.