Potency of progestogens used in hormonal therapy: Toward understanding differential actions

• Available data suggest progestogens differ widely in their biological potencies.
• Off-target receptors, receptor concentrations and metabolism affect potency.
• Affinities do not determine biocharacter but contribute to potency.
• Progestogens exhibit ligand-, cell-, promoter- and assay-specific potencies and biocharacter.
• Potency, efficacy and biocharacter must be defined for each model.

Progestogens are widely used in contraception and in hormone therapy. Biochemical and molecular biological evidence suggests that progestogens differ widely in their affinities and transcriptional effects via different steroid receptors, and hence cannot be considered as a single class of compounds. Consistent with these observations, recent clinical evidence suggests that, despite their similar progestogenic actions, these differences underlie different side-effect profiles for cardiovascular disease and susceptibility to infectious diseases. However, choice of progestogen for maximal benefit and minimal side-effects is hampered by insufficient comparative clinical and molecular studies to understand their relative mechanisms of action, as well as their relative potencies for different assays and clinical effects. This review evaluates the usage, meaning and significance of the terms affinity, potency and efficacy in different models systems, with a view to improved understanding of their physiological and pharmacological significance.This article is part of a Special Issue entitled ‘Menopause’.