ASSOCIATION BETWEEN VITAMIN D DEFICIENCY AND PREMATURE OVARIAN AGING: A CROSS-SECTIONAL STUDY

JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 18, issue 01, 2025 ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431 www.wordlyknowledge.uz ILMIY METODIK JURNAL Doniyorova Ch.T. Republican specialized scientific and practical medical center for maternal and child health. ASSOCIATION BETWEEN VITAMIN D DEFICIENCY AND PREMATURE OVARIAN AGING: A CROSS-SECTIONAL STUDY Abstract:Vitamin D deficiency has been increasingly linked to ovarian dysfunction and premature ovarian aging (POA). This study aims to assess the relationship between serum vitamin D levels and ovarian reserve markers among reproductive-age women. A total of 140 women aged 22–38 years were evaluated for serum 25(OH)D, AMH, FSH, and estradiol levels. Vitamin D deficiency (<20 ng/mL) was significantly associated with lower AMH and higher FSH, suggesting that vitamin D insufficiency may accelerate ovarian aging through endocrine and oxidative mechanisms. 1. Introduction Premature ovarian aging (POA) is characterized by a progressive decline in ovarian reserve and reproductive potential before the age of 40. It manifests as menstrual irregularities, reduced fertility, and elevated gonadotropin levels. Traditionally, genetic, autoimmune, and iatrogenic factors have been considered major contributors; however, recent research indicates that vitamin D deficiency may play an underrecognized but critical role in ovarian aging. Vitamin D, a secosteroid hormone, regulates not only calcium homeostasis but also reproductive function, as vitamin D receptors (VDR) are expressed in ovarian granulosa cells, endometrium, and placenta. Experimental studies show that vitamin D modulates AMH gene expression, promotes follicular growth, and reduces oxidative stress in the ovarian microenvironment. Hence, chronic vitamin D deficiency might lead to accelerated follicular atresia and early reproductive senescence. 2. Objective To evaluate the association between serum vitamin D levels and ovarian reserve parameters in reproductive-age women, and to determine whether vitamin D deficiency independently predicts premature ovarian aging. 3. Materials and Methods 3.1 Study design and participants This cross-sectional study included 140 women aged 22–38 years who attended the Reproductive Endocrinology Clinic of Tashkent Medical Academy between January and June 2025. Inclusion criteria were regular menstrual cycles and absence of known endocrine disorders. Exclusion criteria included polycystic ovary syndrome (PCOS), autoimmune disease, and history of chemotherapy or pelvic surgery. 3.2 Laboratory measurements JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 18, issue 01, 2025 ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431 www.wordlyknowledge.uz ILMIY METODIK JURNAL Venous blood samples were collected on days 2–3 of the menstrual cycle. Serum levels of 25hydroxyvitamin D [25(OH)D], Anti-Müllerian Hormone (AMH), Follicle-Stimulating Hormone (FSH), and estradiol (E2) were measured using enzyme-linked immunosorbent assay (ELISA). Vitamin D deficiency was defined as <20 ng/mL and insufficiency as 20–30 ng/mL. 3.3 Ultrasound assessment Transvaginal ultrasonography was performed using a 7.5 MHz probe to determine Antral Follicle Count (AFC). Ovarian volume was also measured by 3D reconstruction. 3.4 Statistical analysis Data were analyzed using SPSS v.27. Continuous variables were expressed as mean ± SD. Group comparisons were performed using Student’s t-test, and correlations were analyzed using Pearson’s coefficient. Multivariate linear regression was applied to identify independent predictors of low ovarian reserve. A p-value <0.05 was considered statistically significant. 4. Results The mean age of participants was 29.4 ± 4.2 years. Vitamin D deficiency was detected in 63.6% of the women. Those with vitamin D deficiency showed: - Significantly lower AMH levels (1.12 ± 0.47 ng/mL) compared to the sufficient group (2.56 ± 0.69 ng/mL; p < 0.001), - Higher FSH levels (10.3 ± 2.1 IU/L vs. 6.9 ± 1.8 IU/L; p < 0.01), - Decreased AFC (4.8 ± 1.6 vs. 7.9 ± 2.3; p < 0.01). A strong positive correlation was observed between serum 25(OH)D and AMH (r = 0.51, p < 0.001), while FSH levels were inversely correlated with vitamin D (r = –0.44, p = 0.002). After adjustment for age and BMI, vitamin D deficiency remained an independent predictor of diminished ovarian reserve (β = –0.34, p = 0.004). 5. Discussion Our findings support the growing evidence that vitamin D deficiency may accelerate ovarian aging. The mechanism likely involves oxidative stress and altered AMH signaling. Vitamin D enhances expression of AMH receptors and suppresses apoptosis in granulosa cells. Its deficiency increases reactive oxygen species (ROS), leading to mitochondrial dysfunction and follicular atresia. The observed correlation between low vitamin D and high FSH aligns with previous studies by Irani et al. (2015) and Fabris et al. (2020), which also demonstrated reduced ovarian responsiveness in vitamin D–deficient women. Given the high prevalence of vitamin D deficiency in Central Asia, these findings have public health significance for reproductive-age women. JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 18, issue 01, 2025 ISSN: 2181-4341, IMPACT FACTOR ( RESEARCH BIB ) – 7,245, SJIF – 5,431 www.wordlyknowledge.uz ILMIY METODIK JURNAL 6. Conclusion Vitamin D deficiency is significantly associated with premature ovarian aging, manifested by reduced AMH, increased FSH, and lower follicle count. Regular screening of vitamin D status and appropriate supplementation may represent a preventive strategy to delay ovarian senescence and improve fertility outcomes. 7. References (Vancouver Style) 1. Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: A systematic review. Fertil Steril. 2015;104(2):458–468. 2. Fabris A, Pacheco A, Cruz M, et al. Vitamin D and assisted reproduction: A systematic review. Reprod Biol Endocrinol. 2020;18(1):77. 3. Luk J, Torrealday S, Neal Perry G, Pal L. Relevance of vitamin D in reproduction. Hum Reprod. 2012;27(10):3015–3027. 4. Aghajanova L, et al. The role of vitamin D in reproduction: A narrative review. Gynecol Endocrinol. 2019;35(2):95–100.