RU-486: THE REST OF THE STORY
by Dr. Eugene Diamond
RU-486 is one of a new class of drugs whose function is to block end organ receptors of various hormones. When end organ receptors are blocked, the effect of a hormone and various hormone dependent processes are interrupted or altered. RU-486 blocks various end organ receptors but its principal clinically relevant action is to block progesterone receptors.
Since progesterone is necessary for the maintenance of pregnancy, blocking its effect will result in the termination of the pregnancy. Progesterone is necessary to maintain the endometrium which provides a nourishing bed for the implantation and development of the fetus. With RU-486, progesterone is blocked and the endometrium no longer is able to nourish the developing child, which starves and is sloughed out.
It has taken a while for the manufacturers and researchers dealing with clinical applications of RU-486 to decide on its true mode of action.
RU-486 was first promoted as a "morning after pill" to be used after unprotected intercourse. It was discovered, however, that it was not effective early in pregnancy before progesterone levels had reached a critical threshold.
It was then promoted as a "menstrual regulator" -- i.e. a pill a woman could take every month and not even know if she were aborting, thereby, presumably, relieving her conscience. It was discovered, however, that RU-486 causes the phenomenon of "dyssynchrony" in which a woman's ovulatory and menstrual cycles become unlinked -- reducing the drug's effectiveness in terminating any pregnancy.
In 1987, Dr. Beaulieu, the discoverer of RU-486, boasted that RU-486 would completely replace surgical abortions in the first 10 weeks of pregnancy, which is when 80 percent of surgical abortions take place. As a matter of fact, the drug does not work very well after the seventh week of pregnancy and is really only safe and effective when taken during a three week window of opportunity from the fourth to the seventh week. In addition, the drug is not recommended for women over age 35.
When given to induce abortion during the first weeks, RU-486 works about 60 percent of the time. When combined with prostaglandin it is effective about 80 percent of the time. A second course of prostaglandin will abort an additional 15 percent and the remaining 5 percent will require a surgical abortion.
Six or Seven Visits
According to an International Inquiry Commission on RU-486 convened in Paris,1 the proper use of RU-486 involves not a simple home administration of pills but actually a potential six or seven visits to the physician or clinic in order to:
1. Confirm the pregnancy and take RU-486 under supervision.
2. Spend 12 hours in the hospital for prostaglandin injections.
3. Expel the fetus, with resultant hemorrhage and discomfort in 80 percent of cases.
4. Obtain repeat prostaglandin injections in 20 percent of patients.
5. Obtain surgical abortion on those in whom both drugs are ineffective.
6. Undergo ultrasound examination several days later to make sure all parts of the unborn child have been expelled.
In 5 to 10 percent of cases another admission to the hospital will be necessary to control and treat excessive hemorrhage.
Bleeding occurs in over 90 percent of women taking RU-486. Excessive hemorrhage may lead to the need for transfusion and/or D&C.
The next issue beyond ease of administration and simplicity of use is the question of safety. Putting aside the routine side effects of nausea, vomiting and uterine cramps and inevitable hemorrhage (which can be trivialized or maximized depending on one's ideological viewpoint) the real issue of safety centers on the necessity for employment of prostaglandins.
Nobody believes that the use of prostaglandins is safe and innocuous. These are highly active biological compounds which have marked cardiovascular actions requiring close supervision. There is a statement prepared by a joint committee of the French Republic signed by the Director of General Health, the Director of Hospitals and the Director of Pharmacy and Medicine2.
RU-486, CPR and ICU
This directive requests that whenever prostaglandins are given, cardiopulmonary resuscitation equipment and electrocardiographic machines be at standby, a defibrillator be available, calcium channel blockers drawn up in a syringe, and vital signs be monitored over a period of several hours.
What this says, in effect, is that prostaglandins be given only in what amounts to an Intensive Care Unit. This communication, which was sent to all physicians and hospitals in France, followed a fatal cardiac reaction to prostaglandins in a woman who had received the drug after RU-486. It is difficult to sustain the notion of safety against the background of such warnings.
In contrast, an article in the New England Journal of Medicine3 concluded RU-486 "is effective and safe." All six authors of this paper are employees of the company which manufactures the drug and will profit from it.
Very little consideration is given, of course, to the safety of the drugs for the unborn child who is intended to be killed. It must be a matter of concern, however, in those instances where the woman changes her mind after taking the drug and where the drug is only partially effective.
Thalidomide-type Deformities
In those cases where the endometrium is partially disrupted, deformities due to impaired nutrition may occur. Also, the drug itself is similar in chemical structure to other teratogens and might be expected to produce deformities. There have been sporadic reports of such abnormalities, mostly limb-bud anomalies similar to those caused by Thalidomide.4
This raises the issue of who will be the experimental animals while this drug is being tested for safety over time. As we know now, the first generation of contraceptives was unsafe due to their estrogen content. The estrogen component was responsible for an unacceptable rate of thromboembolic complications, including stroke, pulmonary embolus and myocardial infarction. This resulted in a response by manufacturers and a dramatic reduction of the estrogen content to the level of mini pills or its elimination entirely in the progestin-only pills.
American women were the guinea pigs during this trial and error period of field testing, just as they were during the scandalous and immoral coverup of the side effects of the Dalkon Shield and other unsafe intrauterine devices.
It is now proposed that RU-486 be made available for the same type of high-risk experimentation. Professor Pierre de Vernejoul, Chairman of the International Inquiry Commission on RU-486 has stated: "The medical and scientific approach has been sacrificed to ideological motives."
In the promotion of RU-486, a clever but unscrupulous technique has been used to discredit opposition. This has been to create a phony confrontation between the "men of science" and the "know nothings." It is alleged in this kind of propaganda that the many scientific uses of RU-486 are being sacrificed to political motives and that science is being stifled or held hostage by some sort of straw man right-to-lifer more interested in fetuses than adult human beings.5
Dr. Beaulieu has been somewhat more honest than some of his radical feminist propagandists in this regard. In accepting his Lasker Award, he made no pretense of marketing the pill as anything other than an abortifacient -- or, as he said euphemistically, a "contragestive."6
It is important to remember that there is no embargo on the use of RU-486 for research in uses other than as abortifacients. The President of Rousell-Uclaf, the manufacturer, has stated that the company can and does make it available for use for other experimental indications.7 The U.S. federal government and the U.S. Food and Drug Administration have said likewise.
Curative Claims
Nevertheless, drumbeats of the alleged effectiveness of mifepristone (RU-486) are used to drown out the abortion arguments.
It has been alleged to be effective in the treatment of brain tumors.8 This is based on an article by Rogelson in which he noted the presence of progesterone receptors in some meningeomas. This observation has not been tested therapeutically.
RU-486 has been shown to block other hormones, particularly cortisol in Cushings Disease. It has been tried in one study by Bertagna9 who states that RU-486 should not be considered a routine alternative for the treatment of Cushings Disease. A similar report by Nieman came to the same conclusion -- i.e. effective but not proven safe.10
The allegation that it might be used in certain hormone dependent tumors, including those in the breast is, thus far, a speculation based on RU-486's mode of action unsupported by any conclusive research.11
Studies on hypertension12 and immunity13 are not only based on actual research but are derived from speculation which is far fetched and probably irrelevant.
All of these studies have been reviewed and evaluated by Dr. Joe McIlhaney of the University of Texas.14 It is important to remember that the F.D.A., since the Thalidomide disaster, has required that every new drug be subjected to progeny studies. That is, the proposed new drug must be shown by animal studies to be safe and effective not only for patient but also safe for her unborn child if she is pregnant.
If RU-486 were proposed as a treatment for Cushings Disease, for example, it could not pass these progeny studies, since it could not be shown to be safe for use by a pregnant woman with Cushings Disease.
Summary
RU-486 is capable of producing the death of a developing unborn child through blocking progesterone receptors and with consequent disruption of the nutrient bed of the endometrium. It is one of a class of drugs which may have other therapeutic uses by way of receptor blockage, but its only established use is for abortifacience.
The use of RU-486 with prostaglandins is a high-risk therapeutic method which would preclude its ever being used by women during pregnancy except under close and complex medical supervision. The current climate in the medical community is typical advocate science with an unwarranted trivialization of potential toxicity and exaggerated claims of scientific breakthrough.
Dr. Eugene F. Diamond is well known as a pediatrician and educator. He is professor of pediatrics, Loyola University Stritch School of Medicine; visiting professor, Rush Medical College; and acting chairman, Department of Pediatrics at Loyola University. He has served as president of the Illinois Academy of Pediatrics and is currently chairman of the Bioethics Section -- American Academy of Pediatrics.
This article originally appeared in the January 1993 issue of Family Resources Center News, Peoria, Illinois, USA. Reprinted with permission.
Bibliography
1 Dunham, S. International Inquiry Commission Condemns RU-486. Wanderer 125:9, 1992.
2 The French Republic. French Official Warn on Use of RU-486. Child & Family 21:102, 1992.
3 Silvestre, L. et. al. Voluntary Interruption of Pregnancy with RU-486. New England Journal of Medicine. 322-645, 1990.
4 Fonseca, W., et. al. Misoprostal Plus Mifepristone. Lancet 338:1594, 1991.
5 Rogelson, W., et. al. Beyond Abortion: RU-486. JAMA 264 1027, 1990.
6 Beaulieu, E. RU-486 As an Antiprogesterone Steroid. JAMA 262:1808, 1989.
7 Dr. Ariel Mouttet, Director of Marketing for Hormonal Drugs. Roussel-Uclaf Pharmaceutical, quoted by Susanne Fowler - Chicago Tribune in "Battle Lines."
8 Poisson, M., et. al. Journal of Neuroendocrinology 1:179, 1983.
9 Bertagna, O., et. al. Pituitary Adrenal Response to RU-486. Journal of Endocrinology and Metabolism 63:639, 1986.
10 Nieman, L.K. Treatment of Cushing's Syndrome with RU-486. Journal of Endocrinology & Metabolism 61:536, 1984.
11 Romieu, S. RU-486 in Advanced Breast Cancer. Cancer 74:455, 1987.
12 Kalimi. The Role of RU-486 in Dexamethasone Induced Hypertension in Rats. J.AM. Physical 256:682, 1989.
13 Rhim, J. Glucocortoids Enhance Viral Transformation of Mammalian Cell. Proceedings of Society for Experimental Biology in Medicine 174:217, 1983.
14 McIlhaney, J. RU-486, Wonder Drug? Insight, Family Research Council, No. 4, Dec. 1991. |
