Megestrol acetate is available as 5 mg, 20 mg and 40 mg tablets and in oral suspensions of 125 mg/ml and 40 mg/ml. It is used at a dose of 5 mg in combination with an estrogen for contraception. Appetite stimulation is achieved with doses ranging from 400 mg to 800 mg a day. Doses used to treat cancer usually range from 40 mg to 320 mg.
Megestrol acetate is a high-affinity, weak partial agonist/antagonist of the AR, where it binds with very similar but slightly less affinity relative to the PR (about 75% of the affinity according to one assay). However, at clinical doses in humans, it appears to behave, for all intents and purposes, purely as an antiandrogen. No androgenic side effects have been observed with the use of megestrol acetate in patients of either sex at doses up to as high as 1,600 mg per day (which is the highest that has been used). Furthermore, it produces detectable androgenic effects in animals only at a dose that is the equivalent of approximately 200 times that typically used for the treatment of prostate cancer in men.
Unlike the case of the AR, megestrol acetate has no significant affinity for the ER. As such, it does not possess the capacity to directly activate the ER. Furthermore, unlike conventional antiandrogens like cyproterone acetate and flutamide, there is relatively little risk of indirectly-mediated estrogenic side effects (e.g., gynecomastia) with megestrol acetate. This is because conventional antiandrogens only suppress androgen activity (which, because androgen and estrogen activities are typically inversely proportional, results in heightened estrogen levels), whereas megestrol acetate suppresses both androgen and estrogen levels at the same time.
^Venner PM (December 1990). "Therapeutic options in treatment of advanced carcinoma of the prostate". Seminars in Oncology17 (6 Suppl 9): 73–7. PMID2259929.
^Lundgren S, Lønning PE, Utaaker E, Aakvaag A, Kvinnsland S (June 1990). "Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer--I. General findings". Journal of Steroid Biochemistry36 (1-2): 99–104. doi:10.1016/0022-4731(90)90118-c. PMID2362454.
^ abGeller J, Albert J, Geller S (1982). "Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue". The Prostate3 (1): 11–5. doi:10.1002/pros.2990030103. PMID6176985.
^Blumenschein GR (December 1983). "The role of progestins in the treatment of breast cancer". Seminars in Oncology10 (4 Suppl 4): 7–10. PMID6230722.
^Alexieva-Figusch J, Blankenstein MA, de Jong FH, Lamberts SW (September 1984). "Endocrine effects of the combination of megestrol acetate and tamoxifen in the treatment of metastatic breast cancer". European Journal of Cancer & Clinical Oncology20 (9): 135–40. PMID6434315.
^Luthy IA, Begin DJ, Labrie F (November 1988). "Androgenic activity of synthetic progestins and spironolactone in androgen-sensitive mouse mammary carcinoma (Shionogi) cells in culture". Journal of Steroid Biochemistry31 (5): 845–52. doi:10.1016/0022-4731(88)90295-6. PMID2462135.
^ abPoyet P, Labrie F (October 1985). "Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate". Molecular and Cellular Endocrinology42 (3): 283–8. doi:10.1016/0303-7207(85)90059-0. PMID3930312.
^Tisell LE, Salander H (February 1975). "Androgenic properties and adrenal depressant activity of megestrol acetate observed in castrated male rats". Acta Endocrinologica78 (2): 316–24. doi:10.1530/acta.0.0780316. PMID1172901.
Raney MS, Anding R, Fay V, Polk G (2000). "A pilot study to assess the use of megesterol acetate to promote weight gain in frail elderly persons residing in long-term care". J Am Med Dir Assoc1 (4): 154–8. PMID12816553.
Deutsch J, Kolhouse JF (July 2004). "Assessment of gastrointestinal function and response to megesterol acetate in subjects with gastrointestinal cancers and weight loss". Support Care Cancer12 (7): 503–10. doi:10.1007/s00520-004-0615-4. PMID15064933.