The improved potency of MGA compared to medroxyprogesterone acetate may be due to increased resistance to metabolism of MGA afforded by its C6(7) double bond (medroxyprogesterone acetate being identical to MGA in structure except lacking this feature).The pharmacokinetics of MGA have been reviewed. Chemistry
MGA, also known as 17α-acetoxy-6-dehydro-6-methylprogesterone or as 17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione, is a synthetic pregnane steroid and a derivative of progesterone. It is specifically a derivative of 17α-hydroxyprogesterone with a methyl group at the C6 position, a double bond between the C6 and C7 positions, and an acetate ester at the C17α position. MGA is the C17α acetate ester of megestrol, which, in contrast to MGA, was never marketed. Analogues of MGA include other 17α-hydroxyprogesterone derivatives such as acetomepregenol, anagestone acetate, chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and nomegestrol acetate. MGA differs from medroxyprogesterone acetate only by its C6(7) double bond. Close analogues of MGA that were never marketed include cymegesolate (megestrol acetate 3β-cypionate) and megestrol caproate. Synthesis
Chemical syntheses of MGA have been published. History
MGA was synthesized at Syntex in 1959. It was derived from medroxyprogesterone acetate, which had been synthesized at Syntex in 1957. MGA was the third synthetic derivative of progesterone to be developed for use as a medication, following hydroxyprogesterone caproate in 1954 and medroxyprogesterone acetate in 1957.
The optimal dosage with maximum effect for appetite stimulation has been determined to be 800 mg/day. The recommended oral dosage of MGA for breast cancer is 40 mg four times per day (160 mg/day total), while the medication is used at an oral dosage of 40 to 320 mg/day in divided doses for endometrial cancer. It has been used at far lower dosages (e.g., 1–5 mg/day oral, 25 mg/month i.m.) in combination with an estrogen for contraceptive purposes. Available forms
MGA is available as 5 mg, 20 mg, and 40 mg oral tablets and in oral suspensions of 40 mg/mL, 125 mg/mL, 625 mg/5 mL, and 820 mg/20 mL. It was used at doses of 1 mg, 2 mg, 4 mg, and 5 mg in combined oral contraceptives. MGA is formulated at a dose of 25 mg in combination with a dose of 3.75 mg estradiol in a microcrystalline aqueous suspension for use as a once-monthly combined injectable contraceptive in women. Contraindications
Contraindications of MGA include hypersensitivity to MGA or any component of its formulation, known or suspected pregnancy, and breastfeeding. MGA is a teratogen in animals and may have the potential to cause fetal harm, such as decreased fetal weight and feminization of male fetuses. Side effects
The most common side effect of MGA is weight gain, with an incidence of 15 to 70% at the high dosages used to treat breast cancer. Other side effects include vaginal bleeding (7–8%), nausea (7%), and edema (5%), as well as others such as dizziness and shortness of breath.