Structure –Function Relationships, Pharmacokinetics, and Potency of Orally and Parenterally Administered Progestogens

Large intersubject variability is found in serum or plasma levels and pharmacokinetic parameters, including bioavailability and half-life, of all the progestogens. Higher bioavailability of a progestogen may result in a lower required dosage and less intersubject and intrasubject variability. A long serum half-life may be associated with a greater protective effect in the event of missed pills and may provide more consistent cycle control. Assessment of progestogen potency is problematic due to the large number of variables and assumptions associated with quantitative and qualitative tests of potency. Difficulties also arise when potency estimates from animal tests are extrapolated to humans. Nevertheless, certain clinical tests in which potency of orally administered progestogens is assessed in women can provide useful information from which optimal therapeutic progestogen doses can be determined. Biologic activities of progestogens, other than progestational effects, have been poorly studied. There is a misconception about progestin androgenicity. This is due primarily to extrapolation of data from rat studies to the human and misinterpretation of data that show effects of progestins on sex hormone-binding globulin and free testosterone. A better understanding of the pharmacokinetics and potency of progestins will help clinicians to choose the optimal type and dose of progestogen for individualized treatment of patients.