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Associations Between Vitamin D Status and Key Reproductive Hormones in Women of Reproductive Age

NAZAROVA, Aziza

Abstract

Vitamin D deficiency is currently recognized as a widespread condition among women of reproductive age. Vitamin D plays a critical role in maintaining female reproductive health, and insufficient levels in expectant mothers have been associated with adverse pregnancy outcomes such as gestational diabetes, preeclampsia, and low birth weight. Numerous studies indicate that vitamin D deficiency influences both insulin synthesis and insulin resistance. Insulin resistance is one of the most prevalent endocrine disorders, particularly among women who are overweight or obese.

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Medicine & Health TRANSNATIONAL JOURNAL Volume IV│ Issue 4 │ 2025 ISSN: 2692-1936 November-December Transnational Journal of Medicine & Health Volume IV │Issue 4 │October-December London, WC28 5AH 2025 Transnational Journal of Medicine & Health Editorial Team Editors-in-Chief 1. Dr. Skender Topi, University 'Aleksander Xhuvani' Elbasan, Albania 2. Katerina Ristoska, Hemodialysis Center of Sistina Nefroplus. Skopje. Macedonia. Editorial board members/reviewers 1. M.D. Ervin Rapushi, University Hospital Center "Mother Theresa" Department of Internal Medicine. Service of Rheumatology, Tirana, Albania 2. Sachin Kumar Samuchiwal, Brigham and Women's Hospital. Harvard Medical School, Boston, MA, United States 3. Associate Professor Rustem Celami, University Aldent, Tirana, Albania 4. Yau Sui Yu, The Open University of Hong Kong, Hong Kong 5. Behzad Foroutan, Shahroud University of Medical Sciences, Shahroud, Iran 6. Dr. Amer Taqa, DBS Dept. College of Dentistry, University of Mosul, Iraq 7. Sc. M.D. Denisa Golemi, Lushnja Regional Hospital, Lushnja, Albania 8. Marco Orsini, Federal Fluminense University, Rio de Janeiro, Brazil 9. Ravi Teja Mandapaka, National Institute of Nutrition, Hyderabad, India 10. Dr. Prema Saldanha, Yenepoya Medical College, Mangalore, India 11. Associate Professor Fadil Gradica, University of Medicine Tirana, Tirana, Albania 12. Associate Professor Besim Boçi, University of Medicine in Tirana, Tirana, Albania 13. M.D. Petraq Mustaqe, American Hospital Fier, Fier, Albania 14. Prof. Assoc. Dr. Admir Jançe, European University of Tirana, Technical Medical Sciences Faculty, Tirana, Albania Transnational Journal of Medicine & Health is a peer reviewed, international journal, an open access journal with rapid publication of articles in all fields of Medicine and Healthcare. The types of articles accepted include original articles, review articles, case reports, and letters to the editor. 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Associations Between Vitamin D Status and Key Reproductive Hormones in Women of Reproductive Age Aziza B. NAZAROVA Bukhara State Medical Institute Named After Abu Ali ibn Sina, Bukhara, Uzbekistan https://doi.org/10.5281/zenodo.17755065 ABSTRACT Vitamin D deficiency is currently recognized as a widespread condition among women of reproductive age. Vitamin D plays a critical role in maintaining female reproductive health, and insufficient levels in expectant mothers have been associated with adverse pregnancy outcomes such as gestational diabetes, preeclampsia, and low birth weight. Numerous studies indicate that vitamin D deficiency influences both insulin synthesis and insulin resistance. Insulin resistance is one of the most prevalent endocrine disorders, particularly among women who are overweight or obese. KEYWORDS Vitamin D; total 25(OH)D; free 25(OH)D; endocrine parameters; reproductive health; FSH; LH; TSH; T3; T4; AMH; 17-hydroxyprogesterone; biochemical indicators; women of reproductive age; correlations. Vitamin D deficiency in women of reproductive age is frequently associated with fertility impairments, menstrual irregularities, and a higher risk of developing uterine fibroids, endometriosis, and polycystic ovary syndrome (PCOS) [1, 2, 4]. It is also linked to increased muscle fatigue, reduced immune function, poorer hair quality, and a heightened risk of obesity and gestational diabetes during pregnancy [3, 6, 7]. In menopausal women, insufficient vitamin D levels may contribute to the development of osteoporosis. Insulin resistance is commonly observed in overweight women of reproductive age, particularly those with android obesity. It can manifest through menstrual disturbances, impaired ovulation, and infertility. Furthermore, insulin resistance increases the likelihood of metabolic syndrome, type 2 diabetes, cardiovascular complications, and gestational diabetes, which may develop during pregnancy [5, 8]. Study Objective The primary aim of this study was to investigate the associations between vitamin D metabolites and a set of key endocrine parameters, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), anti-Müllerian hormone (AMH), and 17-hydroxyprogesterone (17-OHP). In addition, correlations were assessed with selected biochemical indicators reflecting metabolic and physiological status. By examining both total and free 25-hydroxyvitamin D [25(OH)D], the study sought to clarify the extent to which different vitamin D fractions relate to endocrine regulation in healthy women of reproductive age. Materials and Methods The study population consisted of 51 clinically healthy women of reproductive age (mean age: 28 years), with no known endocrine or metabolic disorders. All participants underwent venous blood sampling during the early follicular phase of the menstrual cycle (days 2–5), a standardized time point that minimizes hormonal variability and ensures comparability across subjects. Serum concentrations of total and free 25(OH)D were quantified using validated laboratory assays. Endocrine parameters—including FSH, LH, TSH, T4, T3, AMH, and 17-OHP—were measured using standard immunoassay techniques. Biochemical indicators relevant to metabolic homeostasis and general health were also assessed. To evaluate the strength and direction of associations between vitamin D metabolites and the selected hormonal and biochemical variables, Spearman’s rank correlation coefficients were calculated due to the nonparametric distribution of several parameters. All clinical and laboratory procedures were conducted at the Department of Obstetrics and Gynecology No. 1 of the Bukhara State Medical Institute named after Abu Ali ibn Sino. The study adhered to institutional ethical standards and followed accepted methodological principles for research involving human participants. Results and Discussion Analysis of anthropometric data showed that 34 women (75.2%) presented with android obesity (waist circumference ≥80 cm), while normal waist circumference was observed in 17 women (24.8%). Serum 25(OH)D concentrations ranged from 8.8 to 48.0 ng/ml (mean 46.73 ± 7.63 ng/ml). TJOMH│ Transnational Journal of Medicine & Health │ Volume IV │ Issue 4 page│ 15 ISSN: 2692-1936 (Online) https://opublication.com/index.php/tjomh © 2025, the Author(s). Published by OAP Opublication. This is an open access article under the CC BY license http://creativecommons.org/licenses/by/4.0/. All participants demonstrated 25(OH)D levels below established reference values, regardless of weight status. Vitamin D deficiency was identified in 48 women (56.4%), while insufficiency was documented in 37 women (43.6%). Women with normal body weight exhibited higher serum 25(OH)D levels compared with overweight or obese participants (42.87 ± 4.32 ng/ml; p<0.05). Among women with normal body weight, 8 (26.6%) had vitamin D deficiency, while the remaining 22 (73.4%) had 25(OH)D concentrations within the normal range. In contrast, women with grade 1 and grade 2 obesity demonstrated significantly lower 25(OH)D levels, indicating a pronounced vitamin D deficiency (Table 1). These findings align with existing evidence that increasing adiposity is associated with reduced bioavailability of vitamin D, likely due to its sequestration in adipose tissue. The high prevalence of deficiency among overweight and obese women underscores the need for targeted preventive and corrective strategies in this population. Table 1. Characteristics of the Examined Women by 25(OH)D Status and Correlations with Biochemical Parameters. Indicators Control n30 Serum 25(OH)D level, ng/ml Р Deficiency ˂20 n=30 Lack 20– 30 n=21 Age (years) 32,5±0,9 31,5±1,4 35,8±0,1 р˂0,05 Weight (kg) 91,4±0,5 92,8±0,9* 87,9±1,0 р˂0,05 Height (сm) 165,7±0,8 164,5±0,2 166,9±2,8 р ˂0,05 BMI (kg/m²) м2 34,0±1,7 33,9±2,7* 34,1±7,1 р˂0,05 WC (сm) 88,2±3,8 93,6±5,8* 90,4±3,1 р˂0,05 25(OH)D (ng/ml) 46,9±9,6 23,4±5,6* 17,9±3,5* р˂0,05 Plasma glucose, Fasting (mmol/L) 4,0±0,5 4,2±0,3 5,2±0,7 р˂0,05 Insulin, (IU/L) 7,7±4,0* 12,5±3,7 19,5±7,3* р˂0,05 Note:*р˂0,05 — reliable in relation to the studied group of women. The data presented in Table 1 demonstrate a clear association between increased body weight and a higher prevalence of vitamin D deficiency and insufficiency. Women with normal serum 25-hydroxyvitamin D [25(OH)D] concentrations exhibited a mean body weight of 91.4 ± 0.5 kg, while those classified as vitamin D–deficient had significantly higher body weight, averaging 92.8 ± 0.9 kg (p < 0.05). This trend was also reflected in anthropometric indicators such as body mass index (BMI) and waist circumference, both of which progressively increased as 25(OH)D concentrations declined. These findings are consistent with previous research indicating that excess adiposity is inversely associated with vitamin D status, potentially due to sequestration of vitamin D in adipose tissue and altered metabolic processing. A growing body of literature suggests that vitamin D deficiency may play a role in the development of insulin resistance, chronic low-grade inflammation, and metabolic syndrome [8–9]. Despite substantial interest in the metabolic implications of vitamin D, the specific relationships between vitamin D metabolism and endocrine factors relevant to female fertility—particularly within the context of metabolic disturbances—remain insufficiently elucidated. To address this gap, the present study investigated the correlations between both total and free 25(OH)D concentrations and a range of endocrine markers in healthy women of reproductive age. The analysis revealed that total and free 25(OH)D exhibited comparable patterns of association with key endocrine parameters, liver function indicators, markers of thrombophilia, and hematological variables linked to anemia. These results align with emerging evidence that vitamin D plays a multifaceted role in female reproductive physiology, extending beyond calcium homeostasis to modulation of sex hormone production, ovarian function, and immune regulation. Low or deficient vitamin D levels have been associated with a spectrum of reproductive and gynecological conditions, including uterine fibroids, endometriosis, anovulation, and polycystic ovary syndrome (PCOS). Within this study population, the magnitude and direction of correlations between free and total vitamin D levels and endocrine, hematological, and biochemical markers were largely consistent, suggesting that both biomarkers provide similar insights into physiological status. TJOMH│ Transnational Journal of Medicine & Health │ Volume IV │ Issue 4 page│ 16 ISSN: 2692-1936 (Online) https://opublication.com/index.php/tjomh © 2025, the Author(s). Published by OAP Opublication. This is an open access article under the CC BY license http://creativecommons.org/licenses/by/4.0/. Overall, the findings support the conclusion that measurements of total and free 25(OH)D serve as reliable and informative indicators for evaluating endocrine function and fertility-related health in women of reproductive age. Given the rising prevalence of vitamin D deficiency worldwide, these results underscore the importance of incorporating vitamin D assessment into clinical evaluations of metabolic and reproductive health, as well as the potential relevance of targeted vitamin D optimization strategies for improving endocrine balance and supporting reproductive outcomes. Conclusion The findings of this study underscore the substantial impact of obesity and vitamin D deficiency on the reproductive and metabolic health of women of reproductive age. Excess body weight, particularly in the presence of android obesity, is strongly associated with lower 25(OH)D concentrations, endocrine disturbances, and a higher prevalence of conditions such as insulin resistance, menstrual irregularities, and infertility. These results align with existing evidence that adiposity reduces the bioavailability of vitamin D and contributes to the disruption of hormonal regulation. Both total and free 25(OH)D demonstrated meaningful correlations with reproductive hormones, biochemical parameters, and markers of metabolic health, indicating that vitamin D status—regardless of the measurement method— is an important determinant of female endocrine function. The study further supports the growing body of literature suggesting that vitamin D plays a key role in ovarian physiology, folliculogenesis, and overall reproductive potential. Deficiency or insufficiency may contribute to gynecological disorders such as polycystic ovary syndrome (PCOS), endometriosis, and uterine fibroids, while exacerbating metabolic abnormalities that impair fertility. These findings highlight the importance of early identification and correction of vitamin D deficiency, especially among women who are overweight or obese. Interventions aimed at weight reduction, including sustained lifestyle modifications such as balanced nutrition and regular physical activity, may not only improve metabolic status but also enhance reproductive outcomes. Vitamin D supplementation at therapeutic doses represents an accessible and evidence-based strategy to support endocrine balance, promote menstrual regularity, and potentially improve fertility. For optimal outcomes, overweight and obese women require individualized, evidence-based recommendations and continuous guidance from healthcare professionals, including endocrinologists, gynecologists, nutritionists, and reproductive specialists. An integrated, multidisciplinary approach is essential for preventing long-term complications, ensuring timely correction of metabolic disorders, and promoting reproductive well-being. Further research is warranted to elucidate the mechanisms linking vitamin D metabolism with hormonal pathways and fertility outcomes, particularly in populations at high risk for both obesity and micronutrient deficiencies. TJOMH│ Transnational Journal of Medicine & Health │ Volume IV │ Issue 4 page│ 17 ISSN: 2692-1936 (Online) https://opublication.com/index.php/tjomh © 2025, the Author(s). Published by OAP Opublication. This is an open access article under the CC BY license http://creativecommons.org/licenses/by/4.0/. References 1. Gorbatenko, N. 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