Clinical Utility of Mifepristone: Apprising the Expanding Horizons

Abstract

Mifepristone is a progesterone and glucocorticoid receptor antagonist. Medical abortion with mifepristone and prostaglandin has revolutionized the abortion process extending abortion care to the doors of females. From as low as 2 mg/day to doses extending to 600 mg, from daily dosing to single dosage treatment, mifepristone has a wide perspective in the treatment of various pathologies. Cervical dilatation and myometrial contractility have made the utility of mifepristone feasible for second-trimester termination of pregnancy and induction of labor awaiting Food and Drug Administration approvals. Its anti-progesterone action on the menstrual cycle has a new dimension of use as a contraceptive, as well as use as a menstruation inductive agent. Its role in endometriosis, ectopic pregnancy, and adenomyosis requires more intensive research. Apoptotic action of mifepristone, interference of heterotypic cell adhesion to the basement membrane, cell migration, growth inhibition of various cancer cell lines, decreased epidermal growth factor expression, suppression of invasive and metastatic cancer potential, increase in tumor necrosis factor, downregulation of cyclin-dependent kinase 2, B-cell lymphoma 2, and Nuclear factor kappa B have opened its potential to be explored as anti-cancer treatment and its effects on leiomyoma. The drug needs to be studied more for the prospectus of its anti-glucocorticoid actions in a wider dimension beyond its acquiescence for the treatment of Cushing syndrome.

Estrogen and progesterone in meningioma: Bridging the gap of knowledge

“…Possible side effects of this therapy are hypothyroidism and endometrial hyperplasia, requiring extensive monitoring. 67 Therefore, the authors postulate that progesterone's role in meningiomas is tumorigenesis, a conclusion drawn from the tendency of meningiomas to be benign rather than malignant. The usual recurrences in WHO grades II and III are not associated with progesterone.…”

Uterine fibroids: modern methods of treatment, advantages and complications

“…The main drugs for the treatment of uterine fibroids are the progesterone antagonist mifepristone and gonadotropin-releasing hormone (aGnRH) agonists, the effectiveness of which has been well studied and proven [17], and their use in Russia is regulated by current clinical guidelines [18]. Mifepristone counteracts the action of progesterone, which is necessary for the growth of fibroids [19].…”

Harnessing PROTAC technology to combat stress hormone receptor activation

“…For example, in patients with post-traumatic stress disorder, hypersensitive GR and associated reductions in GC levels have been repeatedly found 13 . Besides implications in neuropsychiatric diseases, altered GC levels play a major role in the progression and metastasis of various types of cancer, Cushing syndrome, and metabolic disease 14 .…”

“…For instance, in patients with psychotic depression, treatment with the clinically available but non-selective GR antagonist mifepristone (MIF) showed promising results, such as rapidly improving depression symptoms 15,16 . However, binding of MIF to the progesterone and androgen receptor and long-term high dosage requirements are considerable disadvantages 14 . In rodents, administration of MIF has proven beneficial to mitigate stress pathology and has been used to study the implication of GR in the dysregulation of the stress response 15,17 .…”