Megestrol acetate (INN, USAN, BAN, JAN) (abbreviated as MGA or MA, and sold mainly under the brand names Megace and Megace ES), also known as 17α-acetoxy-6-dehydro-6-methylprogesterone, is a steroidal progestin and progesterone derivative (specifically, a 17-hydroxylated progesterone) with predominantly progestational and antigonadotropic effects.

Though sometimes referred to simply as megestrol, it is important to clarify that megestrol acetate is not the same as megestrol, which is a closely related but different compound.Megestrol acetate has powerful antiandrogenic and antiestrogenic effects in humans at sufficient doses, capable of decreasing circulating androgen and estrogen concentrations to castrate levels in both sexes and significantly lowering the expression of the androgen receptor (AR) and the estrogen receptor (ER) in the body.

As an example, one study in men with benign prostatic hyperplasia who were treated with 120-160 mg of megestrol acetate per day for 3 to 11 days found average decreases in AR quantity of 73% and 86% in the cytoplasm and nucleus of prostatic cells,respectively.These actions are likely the result of a strong activation of the PR, which suppresses the secretion of the gonadotropins-peptide hormones responsible for signaling the body to produce not only progesterone but also the androgens and the estrogens-from the pituitary gland as a form of negative feedback inhibition, and hence downregulates the hypothalamic-pituitary-gonadal (HPG) axis, resulting in decreased levels of the sex and their associated enzymes, carriers (e.g., sex-binding globulin), and receptors.It is the antiandrogenic and antiestrogenic effects of megestrol acetate mediated by suppression of the HPG axis that are believed to be largely responsible for its beneficial effects against androgen and estrogen-sensitive cancers, respectively.

Megestrol acetate is used mainly as an appetite stimulant in a variety of conditions and as an antineoplastic agent in the treatment of breast, endometrial, and prostate cancers. When given in relatively high doses, it can substantially increase appetite in most individuals, even those with advanced cancer, and is often used to boost appetite and induce weight gain in patients with cancer or HIV/AIDS-associated cachexia. It is also used as a contraceptive in combination with an estrogen at relatively low doses.

In addition to its use in humans, megestrol acetate has been used extensively in veterinary medicine in the treatment of medical conditions in cats and dogs.