Definition
The group of progesterone receptor ligands includes pure agonists, such as progesterone, pure antagonists, and selective progesterone receptor modulators (SPRMs) with agonistic and antagonistic potential.
Effects
Progesterone antagonism or progesterone agonism, depending on the substance and tissue.
Mechanism of action
Binding to the progesterone receptor.
Indications and potential indications
To date, only mifepristone has been approved in many countries Gynecological indications:
- Abortion (mifepristone).
- Uterine fibroid (SPRM, progesterone antagonists).
- Endometriosis (SPRM, progesterone antagonists).
- Breast cancer (progesterone antagonists).
- Estrogen-free contraception (progesterone antagonists).
Non-gynecological indications:
- Cushing’s syndrome
- Glucocorticoid antagonism (burns, glucocorticoid-dependent hypertension, arthritis, glaucoma, viral infections)
- Alzheimer’s disease
- Depression
- Steroid receptor dependent tumor (breast, ovary, prostate and endometrium, glioma and leiomyosarcoma).
Agents
Progesterone agonists:
- Mifepristone (Mifegyne).
- Onapristone (not commercially available)
Selective progesterone receptor modulators:
- Asoprisnil (not commercially available).
Adverse effects
- Uterine ruptures
- Fatigue
- Nausea
- Anorexia
- Vomiting
- Weight loss
- Libido loss
- Gynecomastia in men
- Skin rash
- Cessation of menstrual bleeding
- Hot flashes
Things to know
After the discovery of mifepristone (progesterone antagonist), substances were sought that had organ-selective antiglucocorticoid but also progestagenic properties. Substances were created as SPRMs that no longer have an abortive effect, whose antiglucocorticoid properties are no longer recognizable, and which, on the other hand, block some undesirable effects of progestagenic substances. These include growth-promoting properties in the mammary gland epithelium. The discovery that receptor agonists or antagonists cause different conformational changes in the progesterone receptor, as well as the fact that cofactors and coactivators interacting with the receptor inhibit or activate gene transcription, explains the tissue-selective effects of SPRMs. Mifepristone is not among the pure progesterone antagonists: depending on the cell, coactivators, and signaling cascade, an agonistic effect may also result. The suffix “-isnil” is used to distinguish SPRMs (asoprisnil) from progesterone antagonists. The progesterone antagonists (mifepristone) all have the suffix “-pristone.” Progesterone antagonists can block follicular development, LH secretion and endometrial maturation, these facts give the substances the potential of estrogen-free contraceptives. Nevertheless, progesterone antagonists have limited usefulness as contraceptives because of their potential teratogenic and/or embryotoxic effects. SPRMs are not effective LH secretion blockers which is why they cannot be considered as contraceptives.
