Progesterone is essential for the initiation and maintenance of pregnancy. After the discovery of the progesterone receptor (PR) in 1970, it was realized that a progesterone receptor antagonist would have a major impact on female reproductive health. In 1981, a glucocorticoid receptor antagonist now known as RU 486 (mifepristone) was synthesized. It soon became evident that this antiglucocorticoid also displayed marked antiprogestin activity. Since the discovery of mifepristone, several hundred similar compounds have been synthesized. These compounds may display progesterone agonist, antagonist, or mixed agonist/antagonist activity.
The chemical structure, mechanism of actions, and biological effects of progesterone receptor modulators will be discussed in this topic review. Their clinical applications and adverse effects, and their use for medical termination of pregnancy and emergency contraception are discussed separately. (See "Therapeutic use and adverse effects of progesterone receptor antagonists and selective progesterone receptor modulators" and "First trimester medication abortion (termination of pregnancy)" and "Emergency contraception", section on 'Antiprogestins'.)
In this topic, progesterone receptor antagonists are referred to as PAs and compounds with mixed agonist/antagonist activity are referred to as selective progesterone receptor modulators (SPRMs). Collectively, these compounds are known as progesterone receptor modulators (PRMs) (figure 1).
The term SPRM is in keeping with the terminology adapted for selective estrogen receptor modulators (SERMs) and selective androgen receptive modulators (SARMs). (See "Mechanisms of action of selective estrogen receptor modulators" and "Use of androgens and other hormones to enhance athletic performance", section on 'SARMs'.)
From a pharmacological, biochemical, and clinical perspective, a SPRM represents a class of progesterone receptor ligands that exerts clinically relevant, tissue selective, mixed progesterone agonist and antagonist effects, which may be full or partial, on various progesterone target tissues in an in vivo situation depending on the biological action studied (figure 1) .