Vitamin D Deficiency Linked to Endometrial Polyps in Infertile Women: Study Highlights Nonlinear Correlation

"This study was the first to establish vitamin D deficiency as an independent risk factor for the incidence of endometrial polyps in infertile patients. Recognizing modifiable risk factors, such as vitamin D deficiency, could pave the way for developing new strategies to treat polyps or prevent their formation," the researchers wrote.

Endometrial polyps are a common condition that can impact endometrial receptivity in women of reproductive age. Vitamin D influences cell proliferation, differentiation, apoptosis, angiogenesis, inflammation control, and immune modulation, apart from its well-known role in regulating calcium and phosphorus balance. Previous research has linked vitamin D levels to reproductive outcomes and highlighted an association between low vitamin D levels and the occurrence of colorectal and nasal polyps. However, limited evidence exists regarding the relationship between serum vitamin D levels and the incidence of EPs.

To address this gap, Xiqian Zhang, Center for Reproductive Medicine, Guangdong Women and Children Hospital, Guangzhou, Guangdong Province, China, and colleagues sought to investigate whether serum vitamin D levels are associated with EPs incidence in infertile women.

For this purpose, the researchers conducted a cross-sectional study at Guangdong Women and Children Hospital between January 2019 and October 2023, involving 3,107 infertile patients.

The participants included women who underwent hysteroscopy, of whom 642 were diagnosed with endometrial polyps, while 2,465 had a normal uterine cavity. Hysteroscopy findings were used to evaluate the risk of EPs, polyp size, the prevalence of multiple polyps, and the incidence of chronic endometritis (CE). Serum vitamin D levels were measured using chemiluminescence to determine total 25(OH)D concentrations.

Patients were categorized into two groups based on international guidelines for vitamin D deficiency: those with serum 25(OH)D levels below 50 nmol/L and those with levels equal to or above 50 nmol/L.

The study led to the following findings:

• Among the participants, 23.8% were vitamin D deficient, with serum 25(OH)D levels below 50 nmol/L.
• The incidence of endometrial polyps was significantly higher in the vitamin D-deficient group (<50 nmol/L) compared to those with sufficient levels (≥50 nmol/L), at 24.9% versus 19.3%.
• There were no differences between the two groups in terms of polyp size, the proportion of multiple polyps, or the presence of chronic endometritis (CE).
• After adjusting for confounding factors, having 25(OH)D levels ≥50 nmol/L was associated with a reduced risk of EPs (adjusted OR: 0.733).
• Additional factors influencing polyp incidence included body mass index (BMI), type of infertility, CA125 levels, and CD138-positive plasma cells.
• A positive linear relationship was identified between age and serum 25(OH)D levels through a linear regression model.
• Subgroup analyses revealed a higher risk of EPs in the 25(OH)D <50 nmol/L group compared to the ≥50 nmol/L group in both younger patients (23.8% versus 19.1%) and older patients (28.0% versus 19.9%).
• A smooth curve fitting model indicated a nonlinear correlation between 25(OH)D levels and the risk of EPs, with an optimal threshold of 51.8 nmol/L for 25(OH)D levels.
• Subgroup analyses showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients under 35 years. In contrast, there was a linear correlation in patients aged 35 years or older.

The authors emphasize that their findings should be interpreted with caution, as the study's correlational nature does not establish causality. Furthermore, the strict inclusion and exclusion criteria may limit the generalizability of the results to broader populations, such as premenopausal women or those of different racial backgrounds.

"Further clinical trials and laboratory studies are necessary to explore the role of vitamin D in the development of EPs and to clarify the underlying mechanisms," they concluded.

Reference:

Zhou, R., Zhu, Z., Dong, M., Wang, Z., Huang, L., Wang, S., Zhang, X., & Liu, F. (2024). Nonlinear correlation between serum vitamin D levels and the incidence of endometrial polyps in infertile women. Human Reproduction, 39(12), 2685-2692. https://doi.org/10.1093/humrep/deae241