What is the first-line pharmacologic therapy for ovulation induction in PCOS and why?

• A. Gonadotropins.
• B. Clomiphene citrate.
• C. Metformin.
• D. Letrozole, because it is associated with higher live birth rates and fewer antiestrogenic effects on the endometrium than clomiphene.

Answer: (D)

Letrozole is preferred as the first-line therapy for ovulation induction in PCOS because it tends to produce higher live birth rates and creates a more favorable endometrial environment than clomiphene citrate. It works as an aromatase inhibitor, lowering estrogen production and relieving negative feedback on the hypothalamus, which increases GnRH pulses and stimulates ovulation. Unlike clomiphene, letrozole does not have antiestrogenic effects on the endometrium, so the lining remains more receptive for implantation. While other options like gonadotropins or metformin are used in certain situations, they come with higher costs, injection administration, and greater risks or metabolic considerations, making letrozole the preferred initial choice in most PCOS patients seeking ovulation.