Progestagens are applied as antitumor therapy for breast and endometrial cancer in case other hormonal therapies failed. Post-menopausal women with hormone sensitive tumors and metastases can benefit from these "anti-estrogens". The exact mechanism of action is not completely clarified. In doses 100 times higher than physiological levels, progestagens can have a direct antitumor effect mediated via the progesterone receptor. Indirectly, progestagens can inhibit the production of androgens (which can be converted into estrogens) in the adrenal gland.

Megestrol acetate, initially developed as contraceptive, has antitumor activity that may involve interaction with progesterone and glucocorticoidreceptors. It has direct cytotoxic effects on breast cancercells in tissue culture and suppresses luteinising hormone release from the pituitary. Side effects include weight gain (due to edema and increased appetite), disturbances in normal reproductive function.

Medroxyprogesterone acetate (MPA) is a long acting progestogen with indirect action on the hypothalamic-pituitaryaxis consisting of inhibition of gonadotrophin releasing hormone release as well as a directaction on estrogen receptors resulting in the inhibition of cellular proliferation. The growthinhibitory effects of progestins are not cell cycle phase-specific, but may be maximal in the G1phase of dividing cells. The application of very high doses can result in serious side effects such as thrombo-embolism, hypertension, liver function disorders, disturbances in normal reproductive function and edema.