Correspondence
Methotrexate and Misoprostol to Terminate Early Pregnancy
N Engl J Med 1996; 334:399-400February 8, 1996
- Article
To the Editor:
The article by Hausknecht on the use of methotrexate and misoprostol to terminate early pregnancy (Aug. 31 issue)1 and the earlier article by El-Refaey et al. on the induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol (April 13 issue)2 demonstrate the efficacy of medically supervised treatment with oral and vaginal abortifacients as an alternative to surgical therapy. However, with the increasing publicity given to the use of these agents for other medical indications, young women with unwanted pregnancies may turn to these drugs without medical supervision.
Since antiquity, folk remedies have been described for the treatment of “amenorrhea.” The use of alkaloidal extracts derived from the mistletoe plant, pennyroyal oil, nutmeg, and other substances is still common in some cultures. As a result of the experience in Brazil, where hundreds of unfortunate women had incomplete abortions and complications after the self-administration of misoprostol,3,4 we can anticipate similar unsupervised use of these agents in this country. We must be prepared to treat such complications and must use caution when we prescribe these agents for their other accepted indications.
4 ReferencesJeanmarie Perrone, M.D.
University of Pennsylvania, Philadelphia, PA 19104Robert S. Hoffman, M.D.
New York City Poison Center, New York, NY 100161
Hausknecht RU . Methotrexate and misoprostol to terminate early pregnancy. N Engl J Med 1995;333:537-540
Full Text | Web of Science | Medline2
El-Refaey H ,Rajasekar D ,Abdalla M ,Calder L ,Templeton A . Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med 1995;332:983-987
Full Text | Web of Science | Medline3
Costa SH ,Vessey MP . Misoprostol and illegal abortion in Rio de Janeiro, Brazil. Lancet 1993;341:1258-1261
CrossRef | Web of Science | Medline4
Coelho HL ,Teixeira AC ,Santos AP , et al. Misoprostol and illegal abortion in Fortaleza, Brazil. Lancet 1993;341:1261-1263
CrossRef | Web of Science | Medline
To the Editor:
Dr. Hausknecht has described the use of methotrexate and misoprostol to terminate early pregnancy. We are concerned that he describes the risks of methotrexate treatment for the developing fetus as “yet unknown.” He quotes a series of articles describing methotrexate as a substantial teratogen, a fact that has also been documented elsewhere.1-4 There is a period between 6 and 8 weeks of embryonic age when the fetus is particularly sensitive to teratogens; this would translate to 56 to 70 days of gestation. Some women would be receiving the treatment described by Dr. Hausknecht at this critical time.
We are concerned that some patients may not return after the methotrexate therapy and may later deliver children with malformations. It would seem important to inform patients clearly of this risk during counseling.
4 ReferencesJerome Yankowitz, M.D.
Jennifer R. Niebyl, M.D.
University of Iowa Hospitals and Clinics, Iowa City, IA 522421
Methotrexate. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 4th ed. Baltimore: Williams & Wilkins, 1994:568-72.
2
Powell HR ,Ekert H . Methotrexate-induced congenital malformations. Med J Aust 1971;2:1076-1077
Web of Science | Medline3
Diniz EMA ,Corradini HB ,Ramos JLA ,Brock R . Efeitos sobre concepto do metotrexato (ametopterina) administrado à mãe. Rev Hosp Clin Fac Med Sao Paulo 1978;33:286-290
Medline4
Sosa Munoz JL ,Perez Santana MT ,Sosa Sanchez R ,Labardini JR . Leucemia aguda y embarazo. Rev Invest Clin (Mex) 1983;35:55-58
Medline
To the Editor:
The article by Hausknecht raises important questions about drug use and its restriction. One cannot help but draw parallels between this report and that evaluating the use of mifepristone and misoprostol to induce abortion, with very similar results.1
Methotrexate2 is one of the oldest chemotherapeutic agents and has demonstrated activity against numerous types of tumors, including breast cancer, head and neck cancer, and osteogenic sarcoma. In lower doses, methotrexate has clinically important activity against nonmalignant conditions, including psoriasis and rheumatoid arthritis. It is accepted for the treatment of ectopic pregnancy and now appears to be effective for the termination of early pregnancy. Mifepristone3 is an antiprogestational agent originally developed for its potential as an abortifacient. However, mifepristone has now been suggested to have activity in conditions as diverse as breast cancer, meningioma, Cushing's syndrome, and endometriosis.
We now have two agents both of which are useful in a large number of medical situations, including medical abortion. As physicians, what should our appropriate response be? Should we restrict the use of methotrexate and keep patients with cancer or psoriasis from access to it, just because methotrexate can be used as an abortifacient? Or should we recognize that mifepristone may have value outside reproductive medicine and take advantage of the therapeutic potential of a unique agent? Whether one is discussing firearms, nuclear power, chemotherapy, or abortion pills, there is always the possibility of use or misuse. As physicians, we must evaluate each agent in terms of its overall value in patient care and not allow that care to be overshadowed by political or ideological considerations.
3 ReferencesSteven M. Grunberg, M.D.
Fletcher Allen Health Care, Burlington, VT 054011
El-Refaey H ,Rajasekar D ,Abdalla M ,Calder L ,Templeton A . Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med 1995;332:983-987
Full Text | Web of Science | Medline2
Schilsky RL. Antimetabolites. In: Perry MC, ed. The chemotherapy source book. Baltimore: Williams & Wilkins, 1992:301-17.
3
Institute of Medicine (IOM). Clinical applications of mifepristone (RU 486) and other antiprogestins. Washington, D.C.: National Academy Press, 1993.
To the Editor:
The article by Hausknecht presents methotrexate and misoprostol as a “simple approach to the termination of pregnancy [with the] potential to become widely available,” with the encouragement that “this method . . . makes it possible to integrate a woman's personal choice about her pregnancy into the everyday practice of medicine.” This presentation of such a morally, socially, and politically controversial issue as the voluntary termination of fetal life diminishes the Journal's stature as an objective voice of medical progress, and it is personally insulting to many physician readers who view abortion as conflicting with the vows they took on entering the medical profession. Indeed, the Hippocratic oath spoken at my medical school graduation included these words: “I will give no deadly medicine to any one if asked . . . and in like manner I will not give to a woman a pessary to produce abortion.”1
Today's social and cultural milieu may have made the tolerance of abortion more acceptable to some under certain circumstances, but to suggest that the voluntary termination of fetal life should become part of “the everyday practice of medicine” should send a chill down the spine of each of us dedicated to preserving the sanctity of life.
1 ReferencesKim T. Swanson, M.D.
360 San Miguel Ave., Newport Beach, CA 92660To the Editor:
You are to be commended for publishing Dr. Hausknecht's paper on the use of oral methotrexate and misoprostol for the medical termination of pregnancy. It is curious that the paper is attributed to Dr. Hausknecht alone. How many articles in the Journal presenting original clinical research have only a single author? Implicit (and explicit) in this work is the direct threat that researchers in this field may face. Were the author's colleagues intimidated, or did he simply prefer to work alone?
Neil Levitt, M.D.
32270 Telegraph Rd., Bingham Farms, MI 48025Author/Editor Response
Dr. Hausknecht replies:
To the Editor: Drs. Yankowitz and Niebyl address a very real concern that is mentioned explicitly in the lengthy consent form that each patient signs and is carefully repeated in each counseling session before she receives methotrexate. Every patient seen to date has had a complete follow-up, and there have been no ongoing pregnancies. As I mentioned in the article, I have accumulating evidence that after the dose of methotrexate is given there is progressive trophoblastic hydropic degeneration. In each case of “failure” to expel the products of conception, microscopical examination of the evacuated tissue confirmed the presence of tissue degeneration. Furthermore, repeated ultrasound examinations in those patients indicated marked reduction in the growth of the fetal pole or the absolute cessation of such growth. I have now treated more than 500 patients successfully using the described protocol, with a 94.6 percent success rate.
Drs. Perrone and Hoffman raise the question of the unsupervised use of either methotrexate or misoprostol in young women with unwanted pregnancies. If safe options (surgical and nonsurgical) for the early termination of pregnancy were available throughout the country, unfettered by restrictive laws such as those in the state of Pennsylvania, there would be little need to use abortifacient drugs in an unsupervised fashion.
Of course, Dr. Grunberg is quite correct in stating that we must not permit political or ideological considerations to interfere with patient care, but unfortunately the subject of abortion has been so divisive that we now see our senators attempting to restrict the ways in which physicians provide care to their patients.
Richard Hausknecht, M.D.
1075 Park Ave., New York, NY 10128- Citing Articles (1)
Citing Articles
1
Jeanmarie Perrone, Robert S. Hoffman. (1997) Toxic Ingestions in Pregnancy: Abortifacient Use in a Case Series of Pregnant Overdose Patients. Academic Emergency Medicine 4:3, 206-209
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