A COMPARISON OF THE CLINICAL AND METABOLIC OUTCOMES OF METFORMIN ALONE VERSUS METFORMIN COMBINED WITH CALCIUM AND VITAMIN D IN WOMEN WITH POLYCYSTIC OVARY SYNDROME: A QUASI-EXPERIMENTAL STUDY

SANGEETHA V JOICE; ANANTHIN; LEKSHMINATHG; INDU PC

doi:10.22159/ajpcr.2025v18i5.54191

Authors

SANGEETHA V JOICE Department of Biochemistry, Saveetha Institute of Medical and Technical Sciences), Chennai, Tamil Nadu, India. https://orcid.org/0009-0004-3668-4843
ANANTHIN Department of Biochemistry, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
LEKSHMINATHG Department of Obstetrics and Gynaecology, Malabar Medical College Hospital and Research Centre, Modakkallur, Kerala, India.
INDU PC Department of Child Health Nursing, Saveetha College of Nursing, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2025v18i5.54191

Keywords:

Vitamin D,, Metformin, Calcium, Metabolic status, Clinical outcome polycystic ovary syndrome, Polycystic ovary syndrome

Abstract

Objective: This study evaluates the clinical and endocrine effects of metformin alone versus metformin combined with calcium and Vitamin D in women with Polycystic Ovary Syndrome (PCOS). PCOS is associated with insulin resistance, hormonal imbalances, and metabolic dysfunction.

Methods: A quasi-experimental interventional study was conducted on newly diagnosed PCOS women (18–45 years). Participants were divided into two groups: Group I received metformin (500 mg/day), calcium (1000 mg/day), and vitamin D (60,000 IU weekly) for 8 weeks. Group II received only metformin (500 mg/day) for 8 weeks. The study compared changes in homeostatic model assessment of insulin resistance, lipid profile, and clinical parameters from baseline to the end of treatment.

Results: Vitamin D supplementation along with calcium and metformin significantly improved body mass index (BMI) (24.93±3.78–23.84±1.11, p<0.001), waist circumference (WC) (87.83±7.83 cm–81.50±3.04 cm, p=0.007), and fasting glucose (95.48±10.64 mg/dL–92.18±6.43 mg/dL, p<0.001). Total cholesterol decreased (p=0.030), and high-density lipoprotein increased (p=0.029). Menstrual regularity (51.7–65%), acne (50–5%), and hirsutism (38.3–0%) improved significantly.

Conclusion: Vitamin D supplementation with calcium and metformin resulted in significant improvements in BMI, WC, glucose levels, lipid profile, menstrual regularity, acne, and hirsutism in women with PCOS. In contrast, metformin alone did not lead to notable metabolic benefits.

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References

Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37(5):467-520.

Orio F, Muscogiuri G, Ascione A, Marciano F, Baldi M, Colao A, et al. Effects of metformin and myoinositol treatment in women with polycystic ovary syndrome (PCOS): A systematic review. J Clin Endocrinol Metab. 2016;101(9):3508-17.

Palomba S, Falbo A, Zullo F, Orio F Jr. Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: A comprehensive review. Endocr Rev. 2009;30(1):1-50.

Colonese F, Rosa VL, Laganà AS, Vitale SG, Cortinovis D, Bidoli P. Comment on: “Is there a role for vitamin D in human reproduction?” Horm Mol Biol Clin Investig. 2017;29:37-8.

Nicolaysen R, Eeg-Larsen N. The biochemistry and physiology of vitamin D. In: Harris RS, Marrian GF, Thimann KV, editors. Vitamins and Hormones. New York: Academic Press; 1953. p. 29-60.

Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE, et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol. 2004;89-90(1-5):121-5.

Kinuta K, Tanaka H, Moriwake T, Aya K, Kato S, Seino Y. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology. 2000;141(4):1317-24.

Harkness LS, Bonny AE. Calcium and vitamin D status in the adolescent: Key roles for bone, body weight, glucose tolerance, and estrogen biosynthesis. J Pediatr Adolesc Gynecol. 2005;18(5):305-11.

Bouillon R, Carmeliet G, Verlinden L, Van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr Rev. 2008;29(6):726-76.

Krul-Poel YH, Koenders PP, Steegers-Theunissen RP, Ten Boekel E, Wee MM, Louwers Y, et al. Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross-sectional study. PLoS One. 2018;13(12):e0204748.

He C, Lin Z, Robb SW, Ezeamama AE. Serum vitamin D levels and polycystic ovary syndrome: A systematic review and meta-analysis. Nutrients. 2015;7(6):4555-77.

Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, et al. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol. 2011;164(4):575-82.

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7.

Maktabi M, Chamani M, Asemi Z. The effects of vitamin D supplementation on metabolic status of patients with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Horm Metab Res. 2017;49(7):493-8.

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385

Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016;2:16057.

Arora S, Kaur P, Garg R, Kaur M, Rani S. Assessment of vitamin D and calcium levels in women with PCOS: An observational study. Asian J Pharm Clin Res. 2023;16(10):129-32.

Jamilian M, Foroozanfard F, Rahmani E, Talebi M, Bahmani F, Asemi Z. Effect of two different doses of vitamin D supplementation on metabolic profiles of insulin-resistant patients with polycystic ovary syndrome. Nutrients. 2017;9(12):1280.

Trummer C, Pilz S, Schwetz V, Zwerina J, März W, Obermayer- Pietsch B. Effects of vitamin D supplementation on metabolic and endocrine parameters in PCOS: A randomized-controlled trial. J Clin Endocrinol Metab. 2019;104(3):897-905.

Figurová J, Dravecká I, Petríková J, Javorský M, Lazúrová I. The effect of alfacalcidiol and metformin on metabolic disturbances in women with polycystic ovary syndrome. Horm Mol Biol Clin Investig. 2017;29(3):85-91.

Park CY. Vitamin D regulation of adipogenesis and adipose tissue functions. J Nutr Health. 2020;53(2):1-8.

Kong J, Li YC. Molecular mechanism of 1, 25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am J Physiol Endocrinol Metab. 2006;290(5):E916-24.

Foroozanfard F, Jamilian M, Bahmani F, Talaee R, Kavossian E, Asemi Z. Calcium plus vitamin D supplementation influences glucose metabolism and lipid concentrations in overweight and obese women with polycystic ovary syndrome: A randomized controlled trial. Clin Nutr. 2018;37(2):638-45.

Pal L, Berry A, Coraluzzi L, Kustan E, Danton C, Shaw J, et al. Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. Gynecol Endocrinol. 2016;32(8):587-91.

Muscogiuri G, Altieri B, De Angelis C. Shedding light on vitamin D status and its impact on PCOS. Nutrients. 2016;8(9):545.

Sukul S, Bahinipati J, Das AK. Role of vitamin D in etiopathogenesis and metabolic abnormalities seen in polycystic ovarian syndrome. Asian J Pharm Clin Res. 2019 Sep;12(9):215-9. doi: 10.22159/ ajpcr.2019.v12i9.33310

Ghorbani R, Nasri P, Moradi S. The effect of vitamin D supplementation on hematological parameters in women with PCOS. J Endocrinol Res. 2021;45(3):244-52.

Jamilian M, Samimi M, Ebrahimi FA, Aghadavod E, Mansooreh B, Asemi Z. Effects of vitamin D and calcium supplementation on endocrine and metabolic status in women with polycystic ovary syndrome. Horm Metab Res. 2017;49(7):493-8.

Krul-Poel YH, Westra S, Steegers-Theunissen RP, Simsek S. Vitamin D supplementation in women with PCOS: A randomized controlled trial. Hum Reprod Update. 2018;24(6):751-72.

Hajhashemi S, Abbasi F, Kamali K, Ebrahimi R. Effects of vitamin D supplementation on lipid profiles in women with PCOS: A randomized controlled trial. Endocr Res. 2020;45(4):321-9.

Jafari-Sfidvajani S, Ahangari R, Hozoori M, Ghasemi-Tehrani H. Influence of vitamin D supplementation on lipid levels in polycystic ovary syndrome patients: A meta-analysis of randomized controlled trials. Lipids Health Dis. 2020;19(1):134.

Jamilian M, Samimi M, Ebrahimi FA, Jamilian H, Bahmani F, Asemi Z. Vitamin D and calcium co-supplementation reduces hormonal and inflammatory parameters in vitamin D-deficient women with PCOS: A randomized controlled trial. Horm Metab Res. 2019;51(1):20-7.

Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2017;86(3):308-15.

Karadag AS, Ertugrul DT, Tutal E, Akin KO. The effect of vitamin D supplementation on acne and androgen levels in PCOS. Clin Endocrinol (Oxf). 2014;81(5):798-806.

Rashidi BH, Akbari A, Latifi SM. The effect of vitamin D supplementation on androgen levels in PCOS: A randomized controlled trial. Eur J Clin Nutr. 2019;73(2):345-52.

Kotsa K, Yavropoulou MP, Stathopoulos I. Vitamin D and insulin resistance in PCOS: A clinical trial. Endocr Res. 2009;34(3):85-93.

Thys-Jacobs S, Donovan D, Papadopoulos A. Vitamin D and calcium regulation in PCOS. J Clin Endocrinol Metab. 2006;91(5):1740-5.