Following this, there is a gradual decline in MPA levels, and the medication can be detected in the circulation for as long as 6 to 9 months post-injection. The particle size of MPA crystals significantly influences its rate of absorption into the body from the local tissue depot when used as a microcrystalline aqueous suspension via intramuscular injection. Smaller crystals dissolve faster and are absorbed more rapidly, resulting in a shorter duration of action. Particle sizes can differ between different formulations of MPA, potentially influencing clinical efficacy and tolerability. The plasma protein binding of MPA is 88%. It is weakly bound to albumin and is not bound to sex hormone-binding globulin or corticosteroid-binding globulin. The elimination half-life of MPA via oral administration has been reported as both 11.6 to 16.6 hours and 33 hours, whereas the elimination half-lives with intramuscular and subcutaneous injection of microcrystalline MPA in aqueous suspension are 50 and 40 days, respectively. The metabolism of MPA is mainly via hydroxylation, including at positions C6β, C21, C2β, and C1β, mediated primarily via CYP3A4, but 3- and 5-dihydro and 3,5-tetrahydro metabolites of MPA are also formed. Deacetylation of MPA and its metabolites (into, e.g., medroxyprogesterone) has been observed to occur in non-human primate research to a substantial extent as well (30 to 70%). MPA and/or its metabolites are also metabolized via conjugation. The C6α methyl and C17α acetoxy groups of MPA make it more resistant to metabolism and allow for greater bioavailability than oral progesterone. MPA is eliminated 20 to 50% in urine and 5 to 10% in feces following intravenous administration. Less than 3% of a dose is excreted in unconjugated form. With intramuscular administration, the high levels of MPA in the blood inhibit luteinizing hormone and ovulation for several months, with an accompanying decrease in serum progesterone to below 0.4 ng/mL. Ovulation resumes when once blood levels of MPA fall below 0.1 ng/mL. Serum estradiol remains at approximately 50 pg/mL for approximately four months post-injection (with a range of 10–92 pg/mL after several years of use), rising once MPA levels fall below 0.5 ng/mL.