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 antagonist/weak partial agonist 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). Despite its weak intrinsic activity at the AR, at clinical doses in humans, megestrol acetate 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 dosages 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 antiandrogens such as cyproterone acetate and flutamide, there is relatively little risk of indirectly mediated estrogenic side effects (e.g., gynecomastia) with megestrol acetate. This is because megestrol acetate strongly suppresses both androgen and estrogen levels at the same time.
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