Effect of Zinc Supplementation on Insulin Resistance and Clinical Features in Women With Polyendocrine Metabolic Ovarian Syndrome.

Polyendocrine Metabolic Ovarian Syndrome (PMOS) is the most common endocrinopathy inwomen of reproductive age, and is mechanistically anchored in insulin resistance (IR),and drives the downstream cascade of hyperandrogenism, anovulation, dyslipidaemia andlong‐term type 2 diabetes risk. South Asian women ‐including Bangladeshi women ‐ developIR at lower BMI thresholds than other populations and simultaneously carry one of theworld's highest burdens of zinc deficiency (57% of non‐pregnant non‐lactating women).Zinc is structurally required for pancreatic β‐cell insulin synthesis, modulatesinsulin‐receptor signaling and PI3K/Akt‐mediated glucose uptake, and acts as a cofactorfor Cu/Zn‐superoxide dismutase, suppressing the oxidative stress and NF‐κB‐driveninflammation that perpetuate IR in PMOS. Despite this strong mechanistic rationale, norandomised trial of zinc supplementation in PMOS has been conducted in any South Asianpopulation.To evaluate the effect of 12 weeks of oral zinc supplementation, as adjunct to standardconventional therapy, on insulin resistance (HOMA‐IR) and on clinical and biochemicalfeatures of PMOS in Bangladeshi women.A randomised, double‐blind, placebo‐controlled trial will be conducted at the Departmentof Pharmacology in collaboration with the Department of Obstetrics & Gynaecology,Bangladesh Medical University (BMU), Dhaka. Seventy four newly diagnosed women with PMOS(Rotterdam / 2023 ESHRE criteria), aged 18‐45 years, will be randomised 1:1 to receiveelemental zinc 50 mg/day or an identical‐appearing placebo, in addition to standardconventional therapy, for 12 weeks. The primary outcome is change in HOMA‐IR frombaseline to 12 weeks. Secondary outcomes include change in serum zinc, serumtriglycderide, biomarker of oxidative stress (serum malondialdehyde), modifiedFerriman‐Gallwey (mFG) hirsutism score, BMI, and menstrual regularity. Between‐armcomparisons will use unpaired t‐tests / Mann‐Whitney U; within‐arm changes by pairedt‐tests; categorical outcomes by χ²; and the relationship between change in serum zincand changes in HOMA‐IR, mFG and androgen markers by Pearson / Spearman correlation.In conclusion, combining zinc supplementation with the conventional treatment might bepotentially have a safe, low cost, substantial impact on insulin resistance, lipidprofile, oxidative stress and hormonal measures in patients with PMOS.