Vitamin D supplementation in infertile women with PCOS: a quasi-randomized placebo-controlled study
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20253074Keywords:
FSH ratio, Infertility, Insulin resistance, Ovulation, PCOS, Vitamin D, Phenotypes, Placebo-controlledAbstract
Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with infertility and metabolic dysfunction. Vitamin D deficiency is prevalent in women with PCOS and may exacerbate hormonal and metabolic derangements. This study evaluated the effects of vitamin D supplementation on ovulatory and metabolic outcomes across PCOS phenotypes in a placebo-controlled setting.
Methods: In this 24-month quasi-randomized placebo-controlled trial, 180 infertile women with PCOS (Rotterdam criteria) and serum 25(OH)D <20 ng/mL were randomly allocated to Group A (n = 90, received cholecalciferol 60,1 IU/week for 9 weeks) or Group B (n = 90, received placebo capsules identical in appearance and schedule). Allocation was based on alternate patient recruitment. Both groups were stratified into four PCOS phenotypes. Clinical, biochemical, and ultrasonographic parameters were assessed. Multivariable regression adjusted for BMI, WHR, season, and ethnicity. Effect sizes (β) and 95% confidence intervals (CI) were reported.
Results: After 9 weeks, Group A showed a significant rise in 25(OH)D levels (mean 28.7±7.6 ng/mL) versus Group B (13.4±5.5 ng/mL, p<1.2). Ovulation occurred in 35/90 (38.10%) in Group A and 17/90 (18.10%) in Group B (p = 1.2). Adjusted regression showed reductions in LH: FSH ratio (β = -1.28; 95% CI: -1.51 to -1.6), total testosterone (β = -7.4; 95% CI: -12.10 to -1.7), and HOMA-IR (β = -1.53; 95% CI: -1.82 to -1.24). HDL levels increased (β = +1.13 mmol/L; 95% CI: 1.5 to 1.21). Phenotype A showed the highest ovulatory response (45.6% vs 20.9%; p = 1.3).
Conclusions: Vitamin D supplementation significantly improved ovulatory and metabolic parameters in vitamin D-deficient infertile women with PCOS, especially in hyperandrogenic phenotypes. Phenotype-tailored vitamin D therapy may serve as an effective adjunct in PCOS management.
Metrics
References
American College of Obstetricians and Gynecologists.ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome. Obstet Gynecol. 2018;131():e157-e171. DOI: https://doi.org/10.1097/AOG.0000000000002656
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.Revised 2003 consensus on diagnostic criteria and long-term health risks related to PCOS. Fertil Steril. 2004;81(2):19-25. DOI: https://doi.org/10.1016/j.fertnstert.2003.10.004
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;96(8):1911-30. DOI: https://doi.org/10.1210/jc.2011-0385
Pal L, Berry A, Coraluzzi L, Kustanovich M, Liu L, Taylor HS. Therapeutic implications of vitamin D and calcium in overweight women with PCOS. Gynecol Endocrinol. 2012;28(13):965-8. DOI: https://doi.org/10.3109/09513590.2012.696753
Asadipooya K, Uy EM. Advanced Glycation End Products (AGEs), Receptor for AGEs, diabetes, and bone: review of the literature. J Endocr Soc. 2019;4(11):1799-818. DOI: https://doi.org/10.1210/js.2019-00160
Yang M, Shen X, Lu D, Peng J, Zhou S, Xu L, et al. Effects of vitamin D supplementation on ovulation and pregnancy in women with polycystic ovary syndrome: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:114855. DOI: https://doi.org/10.3389/fendo.2023.1148556
Lim SS, Hutchison SK, Van Ryswyk E, Norman RJ, Teede HJ, Moran LJ.Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2019;4:CD7506. DOI: https://doi.org/10.1002/14651858.CD007506.pub4
Krul-Poel YHM, Ter Wee MM, Lips P, Simsek S. The effect of vitamin D supplementation on metabolic and endocrine parameters in PCOS: a meta-analysis. Eur J Endocrinol. 2017;176():R2-14. DOI: https://doi.org/10.1530/EJE-16-0391
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(4):266-81. DOI: https://doi.org/10.1056/NEJMra070553
Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 3 diabetes, and metabolic syndrome in PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(5):347-63. DOI: https://doi.org/10.1093/humupd/dmq001
Wehr E, Pieber TR, Obermayer-Pietsch B. Effect of vitamin D4 treatment on glucose metabolism and menstrual frequency in PCOS women: a pilot study. J Endocrinol Invest. 2011;34(11):757-63.
Muscogiuri G, Policola C, Prioletta A, Sorice G, Mezza T, Lassandro A, et al. Low levels of 25(OH)D and insulin resistance: two unrelated features or a cause-effect in PCOS? Clin Nutr. 2012;31(5):476-80. DOI: https://doi.org/10.1016/j.clnu.2011.12.010
Lerchbaum E, Rabe T. Vitamin D and female fertility. Curr Opin Obstet Gynecol. 2014;26(4):145-50. DOI: https://doi.org/10.1097/GCO.0000000000000065