In late September 2000, the Food & Drug Administration approved the use of RU-486, also known as "the abortion pill." After years of bitter controversy, distribution of RU-486 is expected to begin in the United States around the end of October.

"RU" stands for Roussel-Uclaf, the name of the pharmaceutical corporation that makes the drug. "486" is the chemical substance in the drug, Mifepristone. It was invented in France nearly twenty years ago and has been used primarily to induce abortion in many European women.(1)

RU-486, an anti-progestin, binds itself to progesterone receptors on the wall of the uterus and blocks the effect of the woman's natural progesterone. The inhibition of progesterone triggers the shedding of the uterine wall, much like a normal menstruation. The primary function of Progesterone, known as "the pregnancy hormone," is to relax the uterine muscle and increase the supply of blood so that sloughing of the endometrium lining of the uterus does not occur. The relaxed state of the muscle and the thick blood lining provides a comfortable environment for an embryo to implant and grow.

During pregnancy, the progesterone hormone is produced in the placenta in large quantities in order to maintain the proper environment for the embryo to grow. Progesterone inhibits the synthesis of prostaglandins, which are hormones that induce uterine contraction. By inhibiting this activity, uterine contraction decreases and a new follicle is not released. Sharply decreasing levels of Progesterone just before a woman's period is what stimulates the sloughing of the uterine endometrium during menstruation in the case of no pregnancy.

Because RU-486 competitively binds better than progesterone does to the receptor, progesterone is then not able to bind to its own receptor when it reaches the membrane of the uterine cells. RU-486 acts as an antagonist to Progesterone and in doing so actually blocks the action of progesterone. Molecules that mimic the action of a natural molecule are called "agonists;" those that oppose it are "antagonists."(2)

In addition to its use in abortion, RU-486 is also showing promise as a potentially effective treatment for a range of serious diseases and medical conditions, many of which particularly affect women, including Endometriosis.

In a report published in the June, 1998 American Journal of Obstetrics & Gynecology, investigators Kettel, Murphy, Morales and Yen presented preliminary findings on the treatment of Endometriosis with low-dose Mifepristone(3).

In prior studies, authors had previously shown that treatment with Mifepristone, 50 to 100 mg daily, resulted in amenorrhea, anovulation, and symptomatic improvement in women with Endometriosis. In this current study, authors lowered the dose to 5 mg daily to determine whether clinical efficacy was altered without other adverse actions. After 6 months of therapy, Laparoscopy was performed. The results showed that pelvic pain improved in six of seven patients. Cyclic bleeding ceased in all patients, but four of the seven patients complained of irregular bleeding. Surgical staging at the conclusion of the study (five of seven patients) did not detect a change in Endometriosis. Investigators concluded that "Mifepristone, 5 mg daily, resulted in symptomatic improvement, but did not stabilize the endometrium. From our experience with three doses of Mifepristone, we would recommend a dose of 50 mg be used for continued investigations."

In addition to its anti-progestin and anti-glucocoritcoid properties, RU-486 is a non-competitive anti-estrogen. As such, RU-486 blocks the capacity of the endometrial tissue to grow in response to estrogen, making Mifepristone a possible hormonal treatment for Endometriosis.(4)

Other uses for RU-486 include:

Meningiomas: Meningiomas account for 15% of all primary brain tumors and 12% of all spinal cord tumors. Meningiomas occur two times more frequently in women than men.(5)

Leiomyomas: Researchers believe RU-486 is a promising treatment option for fibroid tumors.(6) In one clinical study, researchers found that Mifepristone reduced the average size of uterine fibroid tumors and that the drug was well tolerated by the women who participated in the study.(7)

Breast & Ovarian Cancer: Experts estimate that Mifepristone may be an effective treatment in 40% of breast cancer tumors. In animal studies in the Netherlands, Mifepristone reduced breast cancer tumors as effectively as tamoxifen. In that research, the administration of both tamoxifen and Mifepristone reduced tumors size more than each drug alone.(8)

Laboratory trials conducted in New Jersey suggest that RU-486 may inhibit the proliferation of ovarian cancer cells.(9)

Cushing's Syndrome: Cushing's Syndrome is a potentially fatal over-production of the cortisol hormone. The vast majority of Cushing's Syndrome victims are women, primarily in their 20s to 40s.(10) Some forms of the deadly Cushing's Syndrome can be treated with RU-486.

HIV: Some studies indicate that the cortisol hormone plays a key role in the replication of the HIV virus. Elevated serum cortisol has been found at all stages of HIV-infection, particularly in late-stage HIV (AIDS) patients.(11) One in vitro study showed that by blocking cortisol, Mifepristone lessened the infectivity of HIV and reduced the production of HIV by the already infected cells by 70%.(12)

As an anti-glucocorticoid, RU-486 may prove effective in treating several additional conditions and diseases that are caused by elevated levels of cortisol. These health problems include depression, alcoholism, substance abuse, anorexia nervosa, ulcers, diabetes, Parkinson's disease, multiple sclerosis, and Alzheimer's.(13)

For more information as investigations and research continue on this possible new treatment for Endometriosis, please contact the Endometriosis Research Center at:

http://www.endocenter.org

References:
(1) & (2) "The abortion pill explained;" University of California at Berkeley, U-WIRE; October 05, 2000
(3) A preliminary report on the treatment of Endometriosis with low-dose Mifepristone (RU 486). Am J Obstet Gynecol 1998 Jun;178(6):1151-6 (ISSN: 0002-9378); Kettel LM; Murphy AA; Morales AJ; Yen SS
(4) Kettel M, Murphy AA, et al. Clinical efficacy of the antiprogesterone RU-486 in the treatment of Endometriosis and uterine fibroids. Human Reproduction, 1994.
(5) Association for Brain Tumor Research.
(6) Grunberg SM, et al. Role of antiprogestational therapy for meningiomas. Human Reproduction, 1994.
(7) Murphy et al. Regression of uterine leiomyomata in response to the antiprogesterone RU-486. J of Clinical Endocrinology & Metabolism, 1993.
(8), (11) & (13) The Feminist Majority Foundation
(9) RU-486 May Treat Ovarian Cancer, Researchers Say. The Reuter Business Report, 2/19/95.
(10) Cushing's Syndrome Association.
(12) Weiner et al. The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product. Proc. Natl. Acad. Science, USA, 4/95

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