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This is a combination therapy consisting of three small-molecule drugs—letrozole, pioglitazone, and metformin. Letrozole is an aromatase inhibitor that reduces estrogen synthesis by inhibiting the enzyme aromatase, thereby increasing gonadotropin secretion and stimulating ovulation. Pioglitazone is a thiazolidinedione that acts as an agonist at peroxisome proliferator-activated receptor gamma (PPARγ), improving insulin sensitivity in peripheral tissues. Metformin is a biguanide antihyperglycemic agent that decreases hepatic glucose production and increases insulin sensitivity. This combination has been studied primarily for the treatment of women with polycystic ovary syndrome (PCOS) who are resistant to clomifene citrate, aiming to improve ovulation rates and fertility outcomes by addressing both hormonal imbalance and insulin resistance[1][7]. The regimen has shown efficacy in inducing ovulation among women with PCOS resistant to standard therapies[1].
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