Immunopharmacology of ulipristal as an emergency contraceptive.

A new progesterone antagonist, ulipristal has been made available as an emergency contraceptive. Ulipristal's major mechanism of action as an emergency contraceptive has been ascribed to its ability to delay ovulation beyond the life span of the sperm. This paper analyzes the potential action of ulipristal (1) when unprotected intercourse and administration of ulipristal occur outside the fertility window and (2) when unprotected intercourse and administration of ulipristal occur at or within 24 hours of ovulation. When unprotected intercourse and the use of a single low dose of ulipristal occur outside of the fertility window, ulipristal behaves like a placebo. When unprotected intercourse and the use of a single low dose of ulipristal occur within the fertility window but before ovulation, ulipristal behaves like an emergency contraceptive by delaying ovulation and thereby preventing fertilization. When unprotected intercourse and the administration of ulipristal occur at or within 24 hours of ovulation, then ulipristal has an abortifacient action. It is proposed that the abortifacient mechanism of a low dose of ulipristal taken after fertilization but before implantation is due to the ability of ulipristal to block the maternal innate immune system to become immunotolerant to the paternal allogenic embryo. Progesterone's critical immunotolerant actions involving early pregnancy factor, progesterone-induced blocking factor, and uterine natural killer cells are compromised by ulipristal.

The role of fetal microchimerism in autoimmune disease.

Fetal microchimerism occurs in normal human reproduction and is a relatively new discovery in biology. Recent data in the scientific and medical literature indicates that some of the autoimmune diseases that show a predilection for women in their child-bearing years and beyond are linked to fetal microchimerism from previous pregnancies. The pathological role of fetal microchimeric progenitor immature T cells in autoimmune disease in women is explored. Fetal microchimerism is increased in women who had a termination of pregnancy and may be associated with the development of autoimmune disease later on in life. Furthermore, the consistently rising incidence of autoimmune diseases in women over the past four decades may be attributed to the increase in the utilization of abortion.

Pathopharmacology of excessive hemorrhage in mifepristone abortions.

OBJECTIVE: To explain a pathopharmacologic mechanism that initiates an increase in hemorrhage following medical abortions with mifepristone. DATA SOURCES: MEDLINE, PubMed, and Google Scholar databases were searched (1990-July 2007). Key search terms were mifepristone, RU486, medical abortion hemorrhage, bleeding, inflammation, innate immune system, phagocytes, macrocytes, cytokines, interleukins, and nitric oxide. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathopharmacology of mifepristone as the initiating cause of increased hemorrhage in medical abortions. Mifepristone's blockade of glucocorticoid receptors, prolonged generation of nitric oxide (NO), and postabortion vasodilatation of uterine vasculature by NO that favors excessive hemorrhage were the criteria used to determine whether information was relevant for inclusion. DATA SYNTHESIS: Inescapable bacterial contamination of the decidua accompanies spontaneous, surgical, and mifepristone abortions and is routinely overcome by activation of the innate immune system. The combination of the induction of NO synthase (NOS) and local production of NO is one of the key features of the activation of the innate immune system's phagocytes. NO is a potent vasodilator and is associated with menstrual menorrhagia. Glucocorticoids prevent the overproduction of NOS and NO and thereby contribute to the control of hemorrhage in the postabortion phase. CONCLUSIONS: Blockade of the glucocorticoid receptors by mifepristone can result in an excess of NO that is theorized to be the cause of excessive hemorrhage seen in mifepristone abortions.

Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii.

OBJECTIVE: To explain the role of mifepristone in medical abortions that results in fulminant and lethal septic shock due to Clostridium sordellii. DATA SOURCES: MEDLINE, PubMed, and Google Scholar databases were searched (1984-March 2005). Key search terms were mifepristone, RU38486, RU486, Mifeprex, medical abortion, septic shock, innate immune system, cytokines, and Clostridium sordellii. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathophysiology of mifepristone-induced septic shock due to C. sordellii. DATA SYNTHESIS: The mechanisms of action of mifepristone were incorporated into the pathophysiology of septic shock due to C. sordellii. Mifepristone, by blocking both progesterone and glucocorticoid receptors, interferes with the controlled release and functioning of cortisol and cytokines. Failure of physiologically controlled cortisol and cytokine responses results in an impaired innate immune system that results in disintegration of the body's defense system necessary to prevent the endometrial spread of C. sordellii infection. The abnormal cortisol and cytokine responses due to mifepristone coupled to the release of potent exotoxins and an endotoxin from C. sordellii are the major contributors to the rapid development of lethal septic shock. CONCLUSIONS: Theoretically, it appears that the mechanisms of mifepristone action favor the development of infection that leads to septic shock and intensifies the actions of multiple inflammatory cytokines, resulting in fulminant, lethal septic shock.