WEBVTT 00:00:04.300 --> 00:00:08.290 [The U.S. Department of Health, Education, and Welfare Public Health Service presents T - 1780, V - 1780, MCMLXIX] 00:00:08.290 --> 00:00:12.460 [A National Medical Audiovisual Center Production] 00:00:12.460 --> 00:00:14.100 [Celso-Ramon Garcia, M.C.] 00:00:14.100 --> 00:00:21.000 [Dr. Garcia:] I am Celso-Ramon Garcia, Professor of Obstetrics and Gynecology at the University of Pennsylvania. 00:00:21.000 --> 00:00:28.510 It is my position that the oral contraceptives when prescribed, used, and supervised properly 00:00:28.510 --> 00:00:37.280 present the function for which they were designed with acceptable minimal morbidity. 00:00:37.280 --> 00:00:38.380 [Louis Lasagna, M.D.] 00:00:38.380 --> 00:00:43.800 [Dr. Lasagna:] My name is Louis Lasagna, I'm a clinical pharmacologist from the Johns Hopkins University School of Medicine. 00:00:43.800 --> 00:00:50.610 In my opinion the unpleasant side effects and the very real hazards associated with the oral contraceptives 00:00:50.610 --> 00:00:59.540 are of sufficient magnitude as to constitute a real deterrent to their use as a birth control technique. 00:00:59.540 --> 00:01:00.990 [Sheldon Segal, M.D.] 00:01:00.990 --> 00:01:05.420 [Dr. Segal:] I am Sheldon Segal. I'm the Director of the Biomedical Division of the Population Council 00:01:05.420 --> 00:01:08.180 at the Rockefeller University in New York. 00:01:08.180 --> 00:01:14.300 I shall act as moderator of the discussion of this important and timely topic. 00:01:14.300 --> 00:01:16.130 [Music] 00:01:16.130 --> 00:01:23.010 [Concepts and controversies in modern medicine] 00:01:23.010 --> 00:01:31.750 [The Oral Contraceptives] 00:01:31.750 --> 00:01:36.220 [Host:] Welcome to the exploration of concepts and controversies in modern medicine, 00:01:36.220 --> 00:01:40.760 one of a series of programs dedicated to examining the uncertain, 00:01:40.760 --> 00:01:45.580 candidly recognizing that much of today's teaching is necessarily based upon opinion, 00:01:45.580 --> 00:01:50.470 and that the opinions of eminent physicians in a given field vary widely. 00:01:50.470 --> 00:01:54.920 The National Medical Audiovisual Center believes that openly airing such opposing views 00:01:54.920 --> 00:01:58.910 is a basic responsibility of medical communications. 00:01:58.910 --> 00:02:03.270 Dr. Sheldon Segal, Director of Population Council, Rockefeller University, 00:02:03.270 --> 00:02:07.650 will act as moderator of this presentation. 00:02:07.650 --> 00:02:11.370 [Dr. Segal:] American women are interested in oral contraceptives. 00:02:11.370 --> 00:02:17.650 They are using these drugs at the rate of over 2500 tons a year. 00:02:17.650 --> 00:02:26.910 It is estimated that perhaps one out of every three American women married between the age of 15 and 44, 00:02:26.910 --> 00:02:30.470 has used or is using the oral contraceptive. 00:02:30.470 --> 00:02:35.940 It is being prescribed by virtually every physician in the country. 00:02:35.940 --> 00:02:41.030 On the other hand, we are well aware of the fact that women using this drug 00:02:41.030 --> 00:02:51.900 are not normal with respect to many laboratory parameters of medical normalcy or of physiologic function. 00:02:51.900 --> 00:02:57.100 We know, for example, that several of the circulating hormones 00:02:57.100 --> 00:03:02.220 are not within the normal range in women using oral contraceptives; 00:03:02.220 --> 00:03:07.310 this refers to example to the circulating level of glucocorticoids. 00:03:07.310 --> 00:03:09.810 We are aware of the fact there's an evidence 00:03:09.810 --> 00:03:14.800 of altered carbohydrate metabolism for women using oral contraceptives, 00:03:14.800 --> 00:03:17.450 at least a significant percentage of them. 00:03:17.450 --> 00:03:20.420 There's also evidence of decreased liver function 00:03:20.420 --> 00:03:25.170 as evidenced by certain laboratory tests. 00:03:25.170 --> 00:03:31.630 How is it then, that in the face of this rather perplexing enigma, 00:03:31.630 --> 00:03:34.210 physicians continue to prescribe the drug 00:03:34.210 --> 00:03:39.550 and feel that they are doing so for the well-being of their patients? 00:03:39.550 --> 00:03:42.400 These are some of the issues we would like to explore. 00:03:42.400 --> 00:03:48.730 We will first have a statement from Dr. Garcia. 00:03:48.730 --> 00:03:55.180 [Dr. Garcia:] The ease, convenience and utter effectiveness of the steroid contraceptive 00:03:55.180 --> 00:03:58.290 is universally felt to distinguish it from other forms of contraception. 00:03:58.290 --> 00:04:00.580 [Celso-Ramon Garcia, M.D.] 00:04:00.580 --> 00:04:06.040 Never before in the history of the world have the untoward effects 00:04:06.040 --> 00:04:09.620 of pharmacological agents so consistently 00:04:09.620 --> 00:04:15.810 and so confusingly been presented to a more sophisticated world. 00:04:15.810 --> 00:04:21.940 [inaudible] these issues are the fears of the unknown itself, 00:04:21.940 --> 00:04:29.260 criticisms from the persons opposing contraception in any form, 00:04:29.260 --> 00:04:33.190 and the bias of medical attitudes, 00:04:33.190 --> 00:04:40.830 the belief that pregnancy is good and not associated with hazards, 00:04:40.830 --> 00:04:46.110 and then, further, moral issues are entertained. 00:04:46.110 --> 00:04:53.630 Basically the education of physicians imbues him with the philosophy, 00:04:53.630 --> 00:05:00.330 the need, to preserve life and to avoid harmful approaches. 00:05:00.330 --> 00:05:07.880 This, moreover, is extended to mean that errors of omission 00:05:07.880 --> 00:05:13.900 are less serious, less ominous, 00:05:13.900 --> 00:05:19.730 than the errors and the acts of comission. 00:05:19.730 --> 00:05:24.460 Active contraception, because of this philosophy, 00:05:24.460 --> 00:05:29.620 cannot be favored openly. 00:05:29.620 --> 00:05:34.580 The concept of health however, must consider the composite 00:05:34.580 --> 00:05:40.290 of physical, mental, and social well-being, 00:05:40.290 --> 00:05:47.440 rather than mere absence of infirmity and disease. 00:05:47.440 --> 00:05:51.630 The oral contraceptive by virtue of its utter effectiveness, 00:05:51.630 --> 00:05:55.380 and the convenience which it entertains, 00:05:55.380 --> 00:05:59.600 contributes to the health of the individual, 00:05:59.600 --> 00:06:05.140 despite the many disadvantages that have been pointed to. 00:06:05.140 --> 00:06:10.820 The irresponsible adverse comments about potential harmful effects 00:06:10.820 --> 00:06:15.760 do not contribute to the health of the individual. 00:06:15.760 --> 00:06:20.700 Many of these accusations have been made. 00:06:20.700 --> 00:06:28.400 Moreover, an unabated population press is also menacing. 00:06:28.400 --> 00:06:34.240 Actions of the pill affect all body systems to a greater or lesser degree. 00:06:34.240 --> 00:06:41.080 These actions are a resultant of the combination of the end results 00:06:41.080 --> 00:06:48.040 of both direct effects on target organs as well as the indirect effects, 00:06:48.040 --> 00:06:55.830 which are mediated by alterations induced in the endocrinologically active areas. 00:06:55.830 --> 00:07:00.720 The metabolic alterations that have been discussed 00:07:00.720 --> 00:07:04.030 and pointed to as occurring with the use of the oral contraceptives 00:07:04.030 --> 00:07:10.940 have all been shown to be reversible when these agents are discontinued. 00:07:10.940 --> 00:07:15.920 Many of the reported effects are very difficult to classify 00:07:15.920 --> 00:07:19.860 as to whether they are drug-induced or nondrug-induced. 00:07:19.860 --> 00:07:25.500 Causality and association may not be synonymous. 00:07:25.500 --> 00:07:32.730 The epidemiologic studies of themselves do not resolve the matter convincingly, 00:07:32.730 --> 00:07:38.310 Although there are massive data, there are no truly comparative studies 00:07:38.310 --> 00:07:41.620 nor are the statistics of sufficient validity 00:07:41.620 --> 00:07:47.780 to resolve the association and causality controversy with absolutism. 00:07:47.780 --> 00:07:51.850 Clinical judgment is very much required. 00:07:51.850 --> 00:07:55.690 Physicians cannot shirk their responsibility. 00:07:55.690 --> 00:08:03.750 They must use care and continued supervision in prescribing and in supervising 00:08:03.750 --> 00:08:09.030 and caring for the subjects using this form of contraception. 00:08:09.030 --> 00:08:20.590 There is no effective, no more effective approach to contraception that can be pointed to, 00:08:20.590 --> 00:08:26.790 and prevention of pregnancy must be considered an all or none principle. 00:08:26.790 --> 00:08:32.190 The purported risks of oral contraceptives are of small incidence, 00:08:32.190 --> 00:08:37.340 and by and large are outweighed by the apparent risks 00:08:37.340 --> 00:08:42.230 associated with pregnancy and even the toll of daily living. 00:08:42.230 --> 00:08:46.440 No pharmacological agent can be considered to be totally safe. 00:08:46.440 --> 00:08:59.050 Individuality is cherished, making an ideal contraceptive almost impossible to achieve. 00:08:59.050 --> 00:09:04.550 Many more effective and convenient ones are needed. 00:09:04.550 --> 00:09:07.670 [Dr. Segal:] Dr. Lasagna, would you make your opening statement please? 00:09:07.670 --> 00:09:13.130 [Dr. Lasagna:] Yes, since the beginning of the modern era of chemotherapy, 00:09:13.130 --> 00:09:15.470 since the time of Paul Ehrlich, let us say, 00:09:15.470 --> 00:09:19.160 those interested in the development of new chemicals have been searching for magic bullets, 00:09:19.160 --> 00:09:21.300 [Louis Lasagna, M.D.] 00:09:21.300 --> 00:09:24.970 for drugs that would pick out the offending microorganism 00:09:24.970 --> 00:09:28.320 or would hit a specific organ in the body, 00:09:28.320 --> 00:09:33.020 and leave relatively untouched the rest of the body, 00:09:33.020 --> 00:09:35.580 leave the patient relatively unharmed. 00:09:35.580 --> 00:09:39.250 Almost without exception, perhaps without exception one should say, 00:09:39.250 --> 00:09:43.240 this dream of a magic bullet has not been fulfilled. 00:09:43.240 --> 00:09:47.510 Drugs are more like buckshot than they are like magic bullets, 00:09:47.510 --> 00:09:51.410 and the oral contraceptives in my opinion illustrate this beautifully. 00:09:51.410 --> 00:09:56.300 As has been already said, they seem to hit almost every cell in the body. 00:09:56.300 --> 00:10:01.210 With each passing year we have become aware of the ability 00:10:01.210 --> 00:10:05.920 of these chemicals to affect many parts of the body. 00:10:05.920 --> 00:10:10.320 We have heard of changes in the skin, changes in the hair, 00:10:10.320 --> 00:10:11.930 alterations in libido, 00:10:11.930 --> 00:10:15.490 not always in the appropriate direction. 00:10:15.490 --> 00:10:17.290 We've heard of changes in the liver, 00:10:17.290 --> 00:10:19.240 disturbances in blood-clotting, 00:10:19.240 --> 00:10:21.930 with thromboembolic phenomena manifesting themselves 00:10:21.930 --> 00:10:25.210 in various parts of the body. 00:10:25.210 --> 00:10:29.370 We've heard of depression apparently associated 00:10:29.370 --> 00:10:31.970 with some women with the use of the pill. 00:10:31.970 --> 00:10:35.220 We've heard of severe and excruciating migrainous headaches 00:10:35.220 --> 00:10:39.390 developing in some women for the first time on starting oral contraceptives. 00:10:39.390 --> 00:10:43.850 We are now beginning to develop more and more a fear 00:10:43.850 --> 00:10:50.340 of the potential for development of cancer in either the breasts or the genital tract 00:10:50.340 --> 00:10:55.940 in women exposed for years to these hormones. 00:10:55.940 --> 00:10:59.480 Now when one takes all of those reports, 00:10:59.480 --> 00:11:04.510 and this buckshot capacity of these powerful chemicals, 00:11:04.510 --> 00:11:10.980 and combines that with the knowledge that other methods of contraception are available, 00:11:10.980 --> 00:11:15.020 which, while are not quite as effective as the oral contraceptives, 00:11:15.020 --> 00:11:19.890 are nevertheless, in the hands of many women extraordinarily effective, 00:11:19.890 --> 00:11:25.870 I believe it irresponsible for a physician to look upon these pills 00:11:25.870 --> 00:11:35.610 as a method of first choice for most or all women desiring birth control. 00:11:35.610 --> 00:11:40.490 [Dr. Segal:] Well, we have an interesting situation here in which Dr. Lasagna, 00:11:40.490 --> 00:11:45.120 you believe that it's irresponsible for physicians to be prescribing the pill 00:11:45.120 --> 00:11:47.910 as the contraceptive of first choice, 00:11:47.910 --> 00:11:51.520 and you Dr. Garcia, believe that it's irresponsible 00:11:51.520 --> 00:11:56.460 to be criticizing the potential hazards of the pill. 00:11:56.460 --> 00:12:01.540 [Dr. Lasagna:] I said not for all women as a method of first choice, 00:12:01.540 --> 00:12:04.500 I believe it is the method of first choice for some. 00:12:04.500 --> 00:12:06.220 [Dr. Segal:] Right. 00:12:06.220 --> 00:12:11.620 I think that there probably exists a difficulty here 00:12:11.620 --> 00:12:19.120 in defining just what the precise position of each discussant is. 00:12:19.120 --> 00:12:26.850 Perhaps I could help to resolve this by asking two pointed questions, one to each of you. 00:12:26.850 --> 00:12:32.020 To you, Dr. Lasagna, I would ask do you believe that the oral contraceptives 00:12:32.020 --> 00:12:36.240 as are now being used should be withdrawn from the market? 00:12:36.240 --> 00:12:40.970 And to you, Dr. Garcia, do you believe that the safety of these drugs 00:12:40.970 --> 00:12:46.370 is adequate to permit their widespread use without medical prescription? 00:12:46.370 --> 00:12:48.270 Dr. Lasagna? 00:12:48.270 --> 00:12:50.120 [Dr. Lasagna:] Well, I have for some years now 00:12:50.120 --> 00:12:53.020 been beating the drum, trying to alert people to the possible hazards 00:12:53.020 --> 00:12:54.350 of the oral contraceptives. 00:12:54.350 --> 00:12:58.360 I have never and do not today espouse to physicians 00:12:58.360 --> 00:13:02.100 that these medicaments should be removed from the market. 00:13:02.100 --> 00:13:10.490 I think they continue to play a very important role in birth control. 00:13:10.490 --> 00:13:18.520 [Dr. Garcia:] There is no question that the controversy that exists 00:13:18.520 --> 00:13:24.400 is really not as deep as it appears at first glance. 00:13:24.400 --> 00:13:31.440 On the one hand, it's a matter of how one weighs out the relative merit. 00:13:31.440 --> 00:13:36.350 There is no question that, as I indicated in my opening statement, 00:13:36.350 --> 00:13:41.000 that the physician cannot shirk his responsibility. 00:13:41.000 --> 00:13:46.960 He has to supervise his patients adequately, completely. 00:13:46.960 --> 00:13:50.630 He cannot just prescribe the oral contraceptive, 00:13:50.630 --> 00:13:57.720 nor can the oral contraceptive be dispensed over the counter, nor in slot machines. 00:13:57.720 --> 00:14:04.060 There are sufficient warnings from the studies and epidemiological reviews, 00:14:04.060 --> 00:14:07.240 and while they do not point with absolute [inaudible], 00:14:07.240 --> 00:14:13.300 I quite concur that these must not be left unheeded. 00:14:13.300 --> 00:14:18.630 One must continue to review the problem with this very much in mind. 00:14:18.630 --> 00:14:28.470 However, the aspect of the hazards of not taking the oral contraceptives 00:14:28.470 --> 00:14:30.700 and when I say not taking the oral contraceptive, 00:14:30.700 --> 00:14:36.200 I am really referring to not taking or not using really effective methods of family planning. 00:14:36.200 --> 00:14:42.850 And when you get down below six pregnancies per 100 women a year, 00:14:42.850 --> 00:14:48.970 you are dealing with relatively effective methods. 00:14:48.970 --> 00:14:53.090 Above this, and most of the methods that have been evaluated 00:14:53.090 --> 00:15:00.930 and not associated with the need for a physician, 00:15:00.930 --> 00:15:05.920 are in the category of being relatively ineffective. 00:15:05.920 --> 00:15:09.560 And when you're dealing with this, as I indicated also, 00:15:09.560 --> 00:15:19.130 the need for considering the philosophy that contraception is an all or none principle, 00:15:19.130 --> 00:15:22.500 when a woman comes to me she, doesn't want to be half-safe, 00:15:22.500 --> 00:15:26.230 she wants to have complete protection, this is what she's asking for. 00:15:26.230 --> 00:15:29.970 The unwanted pregnancy raises the great scepter 00:15:29.970 --> 00:15:32.300 [Celso-Ramon Garcia, M.D.] 00:15:32.300 --> 00:15:37.150 and I think here we have increases in maternal and fetal mortality, 00:15:37.150 --> 00:15:40.090 we have increases in other morbidities, 00:15:40.090 --> 00:15:43.820 we have increased hazard of the induced abortion itself, 00:15:43.820 --> 00:15:47.640 even in the best of hands there are hazards with this approach. 00:15:47.640 --> 00:15:52.130 There are increases in the undesirable marriages 00:15:52.130 --> 00:15:56.800 that might result without the availability of effective contraception. 00:15:56.800 --> 00:15:59.030 There are also the trauma and other features 00:15:59.030 --> 00:16:06.660 with regard to illegitimacy and the increase in the undesirable parental behavior 00:16:06.660 --> 00:16:13.230 towards the offspring, which I've seen with great frequency in our society today. 00:16:13.230 --> 00:16:18.080 [Dr. Segal:] Dr. Garcia, I don't think there's any argument about the relative advantages 00:16:18.080 --> 00:16:23.510 to the woman and to the society at large derived from the use of contraception. 00:16:23.510 --> 00:16:29.630 I think it's sometimes unfortunate that people consider as synonyms 00:16:29.630 --> 00:16:33.110 contraception on the one hand and oral contraception on the other. 00:16:33.110 --> 00:16:37.230 Many of the benefits in terms of maternal health of which you speak 00:16:37.230 --> 00:16:42.620 are derived from virtually all effective contraception, 00:16:42.620 --> 00:16:49.990 and for women in many of our socioeconomic classes, effective contraception includes 00:16:49.990 --> 00:16:55.450 not only oral contraception but the intelligent use of the diaphragm, 00:16:55.450 --> 00:16:57.470 use of the intrauterine device, 00:16:57.470 --> 00:17:02.450 and in fact the intelligent use of the method of periodic abstinence. 00:17:02.450 --> 00:17:06.820 But I think that from the response that both of you made, 00:17:06.820 --> 00:17:16.640 it's clear that you have each weighed the equation of relative risk and benefit, 00:17:16.640 --> 00:17:22.720 and come to the conclusion that there is enough safety in the use of oral contraception 00:17:22.720 --> 00:17:29.440 to warrant the continuation of its use in the country. 00:17:29.440 --> 00:17:35.440 So let us focus now on the question of these hazards and risks, 00:17:35.440 --> 00:17:38.600 so that those in the audience can make their own judgments 00:17:38.600 --> 00:17:42.600 about this balance of the hazards on the one hand 00:17:42.600 --> 00:17:45.230 and the effectiveness and usefulness on the other. 00:17:45.230 --> 00:17:47.250 [Dr. Lasagna:] I'd just like to comment on... 00:17:47.250 --> 00:17:48.680 [Dr. Segal:] Sure. 00:17:48.680 --> 00:17:52.790 [Dr. Lasagna:] Dr. Garcia's statement about women wanting 100 percent protection, 00:17:52.790 --> 00:17:55.550 I don't think all women want 100 percent protection, 00:17:55.550 --> 00:18:01.010 and I think this is one of the reasons why there is such a tremendous variability 00:18:01.010 --> 00:18:05.910 in the reports in the literature on the effectiveness of such things as condoms and diaphragms. 00:18:05.910 --> 00:18:12.600 I think the condom and the diaphragm used compulsively 00:18:12.600 --> 00:18:15.790 represent extraordinarily effective techniques. 00:18:15.790 --> 00:18:18.130 But if you're casual about their use, 00:18:18.130 --> 00:18:22.640 if you want a child or two sometime in the future 00:18:22.640 --> 00:18:28.650 and don't really care all that much whether it occurs a year from now or two years from now, 00:18:28.650 --> 00:18:32.390 I think one has a different approach to the use of these mechanical devices 00:18:32.390 --> 00:18:37.730 than the woman who has had four or five children, considers her family complete, 00:18:37.730 --> 00:18:43.010 and is darn likely to be compulsive about the use of these techniques. 00:18:43.010 --> 00:18:47.370 So that I think in the interest of individualizing our approach to these women, 00:18:47.370 --> 00:18:52.230 I think it would be unfortunate to give the impression that every woman wants 100 percent protection... 00:18:52.230 --> 00:18:54.510 [Louis Lasagna, M.D.] 00:18:54.510 --> 00:18:57.340 furthermore, if I can just complete my thought, 00:18:57.340 --> 00:19:01.670 with the oral contraceptives one doesn't have 100 percent protection, 00:19:01.670 --> 00:19:05.020 at least not with the sequential ones, which in my experience, 00:19:05.020 --> 00:19:07.860 the number of anecdotal reports I've come across, 00:19:07.860 --> 00:19:13.040 talking with patients, with obstetricians, the failure rate is significant there. 00:19:13.040 --> 00:19:15.640 The protection is far from complete. 00:19:15.640 --> 00:19:21.380 [Dr. Garcia:] Well, I quite agree that one has to individualize; 00:19:21.380 --> 00:19:28.010 however, I again, the point that one might take at issue here, 00:19:28.010 --> 00:19:31.550 mainly that the patient that has four or five pregnancies 00:19:31.550 --> 00:19:35.520 could likewise be categorized as being in the upper age group, 00:19:35.520 --> 00:19:38.600 where she's going to fall within the category of having greater risk 00:19:38.600 --> 00:19:40.760 with taking the oral contraceptives. 00:19:40.760 --> 00:19:44.710 So it's not such a simple matter, and as a gynecologist, 00:19:44.710 --> 00:19:47.540 I don't know what your experience is as a clinical pharmacologist, 00:19:47.540 --> 00:19:48.780 but as a gynecologist, 00:19:48.780 --> 00:19:53.020 when I query my patients they want an all or none sort of reassurance 00:19:53.020 --> 00:19:59.960 and very few of them elect to take sequential modalities. 00:19:59.960 --> 00:20:03.200 [Dr. Segal:] Can we pass now to the question of the hazards themselves, 00:20:03.200 --> 00:20:09.700 you pointed to Dr. Lasagna's worldwide reputation as a clinical pharmacologist, 00:20:09.700 --> 00:20:13.770 so perhaps we should ask him about some of these issues 00:20:13.770 --> 00:20:18.430 that have been raised with respect to the safety of the pill. 00:20:18.430 --> 00:20:20.320 Let's take the cancer issue first. 00:20:20.320 --> 00:20:25.420 Where does that stand and what are the real facts in that situation, Dr. Lasagna? 00:20:25.420 --> 00:20:27.750 [Dr. Lasagna:] I don't think there are a lot of hard facts to go on here. 00:20:27.750 --> 00:20:32.990 We have a long background of experimental evidence suggesting that hormones 00:20:32.990 --> 00:20:37.280 can be utilized in a number of animal models 00:20:37.280 --> 00:20:40.210 to produce things like breast cancer, that's clear. 00:20:40.210 --> 00:20:45.510 The relevance of these studies to the use of these hormones 00:20:45.510 --> 00:20:48.770 in the variety of clinical states in which they have been used 00:20:48.770 --> 00:20:51.160 for a long time is unclear to me. 00:20:51.160 --> 00:20:55.900 I think we're beginning to have reports on certain changes 00:20:55.900 --> 00:21:03.400 in the cells in the cervix that make one at least worry more 00:21:03.400 --> 00:21:06.070 than we've been worrying in the past, 00:21:06.070 --> 00:21:11.220 and in my opinion at the moment the issue is an open one. 00:21:11.220 --> 00:21:16.470 I think with the background that we have on what these hormones can do in the laboratory, 00:21:16.470 --> 00:21:24.190 it would be foolish to assume that we have no worries, 00:21:24.190 --> 00:21:29.780 but I also would say that at the moment, the evidence implicating these oral contraceptives 00:21:29.780 --> 00:21:35.480 in the production of any kind of cancer is lacking. 00:21:35.480 --> 00:21:38.510 I think the evidence, for example, is much more compelling 00:21:38.510 --> 00:21:41.130 in regard to thromboembolic disease. 00:21:41.130 --> 00:21:50.350 [Dr. Segal:] Still for a moment on the cancer issue--on the basis of the animal work isn't it more likely that the real concern is the breast rather the cervix?, 00:21:50.350 --> 00:21:52.950 [Dr. Lasagna:] I think so, yes. 00:21:52.950 --> 00:21:55.840 [Dr. Segal:] And have there been any clinical observations, 00:21:55.840 --> 00:21:58.600 or let me put it even more fundamentally, 00:21:58.600 --> 00:22:02.900 has anyone actually done a study that would give us some idea 00:22:02.900 --> 00:22:06.350 as to whether or not there is a causal relationship? 00:22:06.350 --> 00:22:08.190 [Dr. Lasagnal:] I'm not aware of any. 00:22:08.190 --> 00:22:13.030 It's a great pity, I think, that so little attention has been paid 00:22:13.030 --> 00:22:17.140 to the setting up of prospective studies to monitor all these things 00:22:17.140 --> 00:22:22.250 that we're concerned about and that we have a hard time making definite statements about, 00:22:22.250 --> 00:22:25.650 because we're stuck with retrospective analysis. 00:22:25.650 --> 00:22:29.480 [Dr. Segal:] You've been mostly involved with this. 00:22:29.480 --> 00:22:36.690 [Dr. Garcia:] Attempts to set up prospective studies have been, in later years, tried... 00:22:36.690 --> 00:22:39.070 One of the greatest difficulties, and one of the things that 00:22:39.070 --> 00:22:46.460 I think is new to most of the scientific world in clinical lines of investigation, 00:22:46.460 --> 00:22:54.910 that is to sample a denominator that is as vast as is required 00:22:54.910 --> 00:22:58.430 to measure small changes in the numerator, 00:22:58.430 --> 00:23:01.550 is indeed a task that I don't know if it would ever be accomplished 00:23:01.550 --> 00:23:04.000 or not with reference to the oral contraceptives. 00:23:04.000 --> 00:23:07.910 There's so many other factors that come into the bias of selection and the like, 00:23:07.910 --> 00:23:15.570 that it's difficult to do this, and what's more to try to have a truly controlled population 00:23:15.570 --> 00:23:21.770 that is not using the steroid contraceptive [inaudible] is likewise very difficult 00:23:21.770 --> 00:23:24.370 because the steroid contraceptive group feel more compelled 00:23:24.370 --> 00:23:28.200 because of the adverse [inaudible] to come back to be seen more frequently. 00:23:28.200 --> 00:23:32.790 While those on other techniques are much more difficult to follow 00:23:32.790 --> 00:23:37.970 and this has been one of the greatest pitfalls that we've had in trying to arrange for prospective studies. 00:23:37.970 --> 00:23:39.480 I don't know how to get around that. 00:23:39.480 --> 00:23:42.200 [Dr. Segal:] But I think that there are good epidemiologic methods 00:23:42.200 --> 00:23:45.230 to account for this bias or to take it into account 00:23:45.230 --> 00:23:47.130 in setting up the design of the study. 00:23:47.130 --> 00:23:52.240 But let me turn to another issue, 00:23:52.240 --> 00:23:58.560 I think the one that has been most firmly established among the possible serious consequences 00:23:58.560 --> 00:24:04.440 of the use of oral contraception has been the epidemiologic studies and indications 00:24:04.440 --> 00:24:11.510 of an increased risk of thromboembolic disease associated with the use of the drug. 00:24:11.510 --> 00:24:15.820 In studies both in Britain, and now on the basis of the recent report by 00:24:15.820 --> 00:24:20.430 the Advisory Committee of Obstetrics and Gynecology of the Food and Drug Administration 00:24:20.430 --> 00:24:23.400 confirmed here in the United States. 00:24:23.400 --> 00:24:29.360 Can you tell us how that stands and what your view of that issue is, Dr. Garcia? 00:24:29.360 --> 00:24:39.100 [Dr. Garcia:] I...there is a strong warning that this presents. 00:24:39.100 --> 00:24:44.870 I don't know that this conclusively proves that there is a cause and effect relationship, 00:24:44.870 --> 00:24:50.910 and I think that as I indicated previously, epidemiologic reviews will not do this. 00:24:50.910 --> 00:25:02.040 We're still lacking many of the mechanisms to explain the occurrence of these thromboembolic and other effects, 00:25:02.040 --> 00:25:09.910 and until this gap has been bridged to demonstrate the mechanism of action that will produce the effect, 00:25:09.910 --> 00:25:13.390 we still will not have a cause and effect relationship, 00:25:13.390 --> 00:25:18.910 but nonetheless these studies are very carefully designed 00:25:18.910 --> 00:25:23.430 and performed according to sound epidemiologic principles, 00:25:23.430 --> 00:25:28.420 and consistently, although with different variants of incidence and points of comparison. 00:25:28.420 --> 00:25:36.800 We have a concurrence with all of the studies indicating an association between the use of oral contraceptives 00:25:36.800 --> 00:25:38.510 and the occurrence of thrombophlebitis, 00:25:38.510 --> 00:25:47.410 and also consistently that risk is seen greater in the older age group than the younger age group. 00:25:47.410 --> 00:25:54.130 [Dr. Lasagna:] May I comment on the quality of the evidence linking the contraceptives to...oral contraceptives to clotting, 00:25:54.130 --> 00:25:57.250 one thing I know something about is the difficulty of linking drugs 00:25:57.250 --> 00:26:00.780 to side effects that are said to be associated with them. 00:26:00.780 --> 00:26:08.630 But in my opinion, the evidence on this point is so good as to be very compelling, 00:26:08.630 --> 00:26:12.230 at least it's so much better than we usually have for other drugs 00:26:12.230 --> 00:26:14.080 that I think one can't ignore the evidence. 00:26:14.080 --> 00:26:17.650 The evidence exists in my opinion, not only in the form of epidemiologic data, 00:26:17.650 --> 00:26:20.380 but in the clotting studies that have been done, 00:26:20.380 --> 00:26:23.280 which in almost all instances have shown a change in women taking these pills 00:26:23.280 --> 00:26:25.560 in the direction of increased clotting. 00:26:25.560 --> 00:26:28.960 The peculiar distribution of some of these clots that they're seeing, 00:26:28.960 --> 00:26:33.980 women coming in with clots in the veins of their arms, a most unusual phenomenon. 00:26:33.980 --> 00:26:36.190 Clots in the vertebral arteries in young women, 00:26:36.190 --> 00:26:39.600 a most unusual neurological picture, and then the challenge cases, 00:26:39.600 --> 00:26:43.510 the women who develop recurrent thrombophlebitis each time they're given the pill. 00:26:43.510 --> 00:26:44.570 There aren't a lot of those, 00:26:44.570 --> 00:26:50.510 but there are enough I think to represent a legitimate challenge type of evidence. 00:26:50.510 --> 00:26:55.310 [Dr. Garcia:] But this sort of bizarre type of location of thromboembolic phenomenon is not new, 00:26:55.310 --> 00:26:58.480 it's just that it hasn't been focused attention on in association 00:26:58.480 --> 00:27:01.380 with the use of oral contraceptives, number one, 00:27:01.380 --> 00:27:08.660 and secondly we have to also consider that... 00:27:08.660 --> 00:27:15.470 [Dr. Segal:] I'm afraid, Dr. Garcia, I'm not going to let you finish your thought because our time is up. 00:27:15.470 --> 00:27:17.360 In the few seconds left to us, 00:27:17.360 --> 00:27:22.350 I'd like to attempt a brief summary of this discussion. 00:27:22.350 --> 00:27:26.380 It seems to me that we have reached a consensus 00:27:26.380 --> 00:27:32.450 that this is a type of medication that does involve risk. 00:27:32.450 --> 00:27:36.740 Both participants agree that the risk is not so great 00:27:36.740 --> 00:27:41.190 to warrant removal of these drugs from the physician's armamentarium. 00:27:41.190 --> 00:27:43.920 I think that both agree also, however, 00:27:43.920 --> 00:27:49.010 that when these drugs are used, they must be used under very careful supervision 00:27:49.010 --> 00:27:55.330 and although the point wasn't raised I feel confident that both would agree 00:27:55.330 --> 00:27:59.130 that the labeling instructions required 00:27:59.130 --> 00:28:04.400 by the Food and Drug Administration should be adhered to very strictly. 00:28:04.400 --> 00:28:13.160 As with all drugs, there is a question of relative risk versus relative advantage in determining safety. 00:28:13.160 --> 00:28:15.720 On that basis and by that definition, 00:28:15.720 --> 00:28:18.520 it seems that there is an element of safety 00:28:18.520 --> 00:28:28.520 sufficient for continuation of the use of oral contraceptives. 00:28:28.520 --> 00:28:33.580 [Host:] We thank Dr. Celso-Ramon Garcia, Dr. Louis Lasagna, and Dr. Sheldon Segal 00:28:33.580 --> 00:28:37.730 for their interesting analysis of a critical problem in patient care. 00:28:37.730 --> 00:28:44.940 In subsequent programs, we shall continue to record equally significant concepts and controversies in modern medicine, 00:28:44.940 --> 00:28:48.820 The opinions expressed on this program do not necessarily constitute endorsement 00:28:48.820 --> 00:28:54.980 by the Department of Health, Education and Welfare, the Public Health Service or its constituents. 00:28:54.980 --> 00:28:55.490 [Music] 00:28:55.490 --> 00:29:01.130 [Celso-Ramon Garcia, M.D., Professor of Obstetrics and Gynecology, Hospital of the University of Pennsylvania] 00:29:01.130 --> 00:29:09.610 [Louis Lasagna, M.D., Associate Professor of Medicine and of Pharmacology and Experimental Therapeutics, Johns Hopkins University School of Medicine] 00:29:09.610 --> 00:29:16.010 [Sheldon Segal, M.D., Director, Population Council, Biomedical Division, Rockefeller University] 00:29:16.010 --> 00:29:23.110 [concepts and controversies in modern medicine] 00:29:23.110 --> 00:35:13.600 [The End, T-1780, V-1780, MCMLXIX]