Pharmacology: The precise mechanism of action by which megestrol acetate produces its antineoplastic effects is unknown at present. Pharmacologic doses of megestrol acetate exerted a direct cytotoxic effect on human breast cancer cells in vitro and proved capable of modifying and abolishing the stimulatory effects of estrogen on breast cancer cell lines. Megestrol acetate interacts with progesterone receptors to stimulate cell maturation through a progestin-inducing mechanism. It has also been shown to have certain androgenic properties and may also modify glucocorticoid action by binding to the glucocorticoid receptor.
In previously untreated breast cancer patients with ER+ PR+ receptor status, endocrine therapy has been shown to produce responses in up to 81% of patients.
Inhibition of persistent endometrial hyperplasia and of persistent endometrial adenocarcinoma was observed upon administration of megestrol acetate in doses of 160 mg/day and megestrol acetate partially inhibited expression of estrogen dependent secretory proteins and certain constituent proteins in the rat uterine epithelium.
Metastatic carcinoma of the prostate responds to a variety of hormone manipulations that decrease the level of androgens in androgen-sensitive tissue.
The primary mechanism of action of megestrol acetate and DES is the suppression of luteinizing hormone from the pituitary gland, which leads to suppression of serum androgens arising from the testicle.
Megestrol acetate may have other mechanisms of action as well, including an antiandrogen activity, suppression of adrenal androgens, and possibly the inhibition of enzymes, eg. 5 -reductase, critical to androgen metabolism within the prostate.