Variability and quantification of serum medroxyprogesterone acetate levels

Quantification of serum progestin levels in clinical contraceptive studies is now routinely performed to under-stand progestin pharmacokinetics and to correct for unreliable self-reporting of contraceptive use by study participants. Many such studies are focussed on the three-monthly progestin-only intramuscular (IM) injectable contraceptive depot medroxyprogesterone acetate (DMPA-IM). Methods commonly used to measure serum MPA levels include liquid chromatography coupled to mass spectrometry (LC/MS) and radioimmunoassay (RIA); however, RIA methods have not been used in recent years. We review the available literature and find that these methods vary widely in terms of use of organic solvent extraction, use of derivitization and choice of organic solvent and chromatography columns. There is a lack of standardization of LC/MS methodology, including a lack of detailed extraction protocols. Limited evidence suggests that RIA, without organic solvent extraction, likely over-estimates progestin levels. Maximum MPA concentrations in the first two weeks post-injection show wide inter-individual and inter-study variation, regardless of quantification method used. Standardization of quanti-fication methods and sampling time post-injection is required to improve interpretation of clinical data, in particular the side effects arising at different times depending on the pharmacokinetic profile unique to injectable contraceptives.

Automated summary

Quantification of serum progestin levels in clinical contraceptive studies is crucial for understanding progestin pharmacokinetics and improving the accuracy of self-reported contraceptive use. Current methods vary widely and lack standardization, leading to potential overestimation of progestin levels. Inter-individual and inter-study variation in maximum progestin concentrations post-injection highlights the need for standardized quantification methods and sampling time.