An Exhaustive Pharmacological and Clinical Review of Megestrol Acetate (DB00351)

Executive Summary & Overview

Introduction to Megestrol Acetate

Megestrol acetate is a synthetic, orally active derivative of the naturally occurring steroid hormone progesterone. It is classified as a first-generation progestin, a class of drugs that mimic the effects of progesterone.[1] Discovered in 1959 and introduced for medical use in 1963, megestrol acetate has carved out a unique and somewhat paradoxical clinical identity over its long history.[1] It functions both as a hormonal antineoplastic agent used in the palliative treatment of specific hormone-sensitive cancers and, more widely, as an appetite stimulant for the management of cachexia and wasting syndromes associated with chronic diseases.[1] This dual functionality stems from distinct pharmacological mechanisms that define its utility and its complex risk profile.

Core Therapeutic Roles and Controversies

The primary therapeutic applications of megestrol acetate are well-defined by regulatory approvals. In oncology, the tablet formulation is indicated for the palliative treatment of advanced, recurrent, or metastatic breast cancer and endometrial cancer.[6] Its role in this setting is to hormonally modulate and suppress tumor growth. In supportive care, the oral suspension formulations are approved for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients diagnosed with Acquired Immunodeficiency Syndrome (AIDS).[6] However, the drug is also at the center of a significant clinical controversy regarding its widespread off-label use for cancer-related cachexia. Despite its frequent prescription for this purpose, a growing body of high-level evidence, including recent meta-analyses and large observational studies, has challenged its efficacy in this patient population, creating a disconnect between historical practice and current data.[9]