The weak but significant androgenic activity of MGA may serve to limit its clinical effectiveness in the treatment of prostate cancer. Glucocorticoid activity
MGA is an agonist of the glucocorticoid receptor (GR), the biological target of glucocorticoids like cortisol. It has been found to possess 30% of the affinity of the corticosteroid dexamethasone for this receptor. MGA shows the lowest ratio of PR affinity to GR affinity of a broad selection of marketed progestins, suggesting that it may have among the highest relative glucocorticoid effect of the progestins used in medicine. MGA produces observable glucocorticoid effects, with one study finding that, in the dose range tested, it possessed about 50% of the eosinopenic and hyperglycemic activity (markers of glucocorticoid activity) of an equal amount of medroxyprogesterone acetate and about 25% that of hydrocortisone. Accordingly, manifestations of its glucocorticoid activity, including symptoms of Cushings syndrome, steroid diabetes, and adrenal insufficiency, have been reported with the use of MGA in the literature, albeit sporadically. Appetite stimulation
MGA is frequently used as an appetite stimulant to promote weight gain. The direct mechanism of appetite enhancement is unclear, but it is known that MGA induces a variety of downstream changes to cause the effect, including stimulation of the release of neuropeptide Y in the hypothalamus, neurosteroid-like modulation of calcium channels in the ventromedial hypothalamus, and inhibition of the secretion of proinflammatory cytokines including interleukin 1α, interleukin 1β, interleukin 6, and tumor necrosis factor α, all of which have been implicated in facilitation of appetite.
Interactions
Interactions of MGA include significantly decreased exposure to indinavir, which may necessitate an increased dosage of the medication. When MGA is co-administered with zidovudine and rifabutin, there is no significant change in exposure to these medications and no dosage adjustment is necessary. Pharmacology
Pharmacodynamics
MGA has progestogenic activity, antigonadotropic effects, weak partial androgenic activity, and weak glucocorticoid activity. Progestogenic activity
MGA is a progestogen, or an agonist of the progesterone receptor (PR). It has about 65% of the affinity of promegestone and 130% of the affinity of progesterone for the PR. Like other progestogens, MGA has functional antiestrogenic effects in certain tissues such as the endometrium and has antigonadotropic effects. The total endometrial transformation dose of MGA is 50 mg per cycle. Antigonadotropic and anticorticotropic effects
MGA has antigonadotropic effects in humans at sufficient doses, capable of profoundly suppressing circulating androgen and estrogen concentrations. The antigonadotropic effects of MGA are the result of activation of the PR, which suppresses the secretion of the gonadotropins—peptide hormones responsible for signaling the body to produce not only progesterone but also the androgens and the estrogens—from the pituitary gland as a form of negative feedback inhibition, and hence downregulates the hypothalamic–pituitary–gonadal axis (HPG axis), resulting in decreased levels of the sex hormones and interference with fertility. As such, MGA has functional antiandrogenic and antiestrogenic effects as well as contraceptive effects via its antigonadotropic effects.The precise ovulation-inhibiting dosage of MGA is unknown.