Long-acting vs monthly GnRH agonists: A comprehensive review of efficacy, safety, and health-system implications

Gonadotropin-releasing hormone (GnRH) analogs are widely used in the treatment of hormone-dependent conditions such as prostate cancer, breast cancer, and central precocious puberty. These agents suppress sex hormone secretion by persistently downregulating the hypothalamic-pituitary-gonadal axis. To improve convenience and adherence, various long-acting injectable formulations, administered monthly, quarterly, or every 6 months, have been developed. However, there is ongoing debate regarding the relative advantages and optimal choice among these formulations.

Evidence from clinical trials and real-world studies suggests that the efficacy and safety of multimonthly formulations are equivalent to or noninferior to those of monthly variants and produce similar clinical outcomes in hormone suppression and disease control. In addition, multimonthly injections are associated with fewer hospital visits, improved adherence to treatment, lower indirect costs, and improved quality of life for patients.

Although differences in pharmacokinetics and initial hormonal responses have been observed, they do not translate into meaningful differences in clinical outcomes. Long-acting GnRH analogs are equally effective and offer a more efficient, patient-centered approach to managing hormone-dependent diseases.