of IUD's and sterilization. Also it should be noted that these data were obtained from married women and differ somewhat from the contraceptive practices of other women.

The first class of contraceptives are various barrier methods, which are designed to prevent access of the sperm to the uterus. All of these methods prevent fertilization. In 1970, approximately 28.3 percent of couples used these methods which include withdrawal, 2.1 percent; douche, 3.2 percent; diaphragm, 5.7 percent; vaginal jellies and foams, 6.1 percent; and the condom, 14.2 percent. Withdrawal involves the deposition of sperm outside the vagina and the other methods involve the use of a physical barrier or some fluid substance to immobilize sperm or wash them from the vagina. It should be noted that the douche is not considered to be a good contraceptive. The second class of contraceptives is rhythm or periodic continence. There are a variety of rhythm methods but all are based on attempts to avoid coitus at the time when fertilization is thought likely to occur. No devices or drugs are used and coitus is normal, but it is restricted to periods in the menstrual cycle during which conception is thought not likely to occur. In 1970, 6.4 percent of couples used this method.

The third class of methods includes the intrauterine devices of which a large variety are in use, including types developed quite recently which contain drugs, such as copper or hormones. In 1970, 7.4 percent of couples used this method, but there probably has been an increase in their use since then.

Little is known with absolute certainty about the mechanism of action of IUD's in humans, but we know much of their mode of action in various experimental animals. The effect varies considerably from species to species, ranging from sheep in which IUD's prevent access of the sperm to the uterus; to rabbits, where devices interrupt the reproductive process after implantation. In most animals, however, IUD's appear to be effective before implantation has occurred. This is the case in rodents, hamsters and non-human primates.

IUD's alter the environment of the uterus so that it is inhospitable to sperm, the ovum or the fertilized ovum, depending on which is most sensitive. The most sensitive element in sheep is sperm, but in most others it is the ovum.

We know little about the mechanism of action in humans. We cannot state with certainty how they work, but many scientists believe that they prevent implantation. Our doubt is confounded by the fact that IUD's are not always effective, and approximately 2 or 3 percent of women with IUD's in place become pregnant within the first year. Thank you for the opportunity to review these important topics. Dr. Douglas intends to discuss the two other main classes of methods. Senator BAYH [presiding]. Why do you not proceed.

PREPARED STATEMENT ON THE MECHANISM OF ACTION OF ORAL CONTRACEPTIVES AND STERILIZATION-GORDON W. DOUGLAS, M.D.

Mr. Chairman, members of the subcommittee, I wish to express my appreciation for the opportunity to present testimony on this subject to the subcommittee. Oral contraceptive pills have been under investigation since 1956, and in approved clinical use since 1960. Today, nearly one third of women practicing birth control employ this method, and the number of present and former users number in the many millions. As a method, oral contraceptives have been char

acterized by a very high degree of effectiveness, approaching 100%, and by a high degree of safety, substantially greater than pregnancy itself.

Oral contraceptives fall into four major categories, based on the components of the pills, and the timing of administration. All contain one or both of two classes of chemical substances, estrogens and progestins, which function in the body as hormones:

1. Combination pills-These contain both estrogen and progestin, and are administered daily for 21 days, with an interruption of 7 days before a new cycle of pill use is begun.

2. Sequential pills-During the first 14 days, estrogen alone is administered, followed by 7 days of use of a combination of estrogen and progestin. Again a 7 day interval precedes the beginning of a new cycle of use.

3. Mini-pills-These contain progestins only, in very small dosage, and are taken continuously.

4. Post-Coital (morning-after) pills-These contain only estrogen in high dosage, and are started within 72 hours of sexual intercourse, and continued for 5 days.

These classes of contraceptive pills have different mechanisms of action, and in some cases more than one mechanism of action, which accounts for the very high degree of effectiveness.

Combination Pills.-In the normal young woman, ovulation coincides with a rapid rise in the blood of luteinizing hormone (LH), which is released by the pituitary gland. This is known as the LH Surge, and without it, ovulation does not occur. The LH surge is effectively blocked by the progestin in these pills, and ovulation does not occur. A second mechamism is exerted by estrogens, which suppress the pituitary hormones responsible for development of the ovarian follicle in which the eggresides. Third, the progestin component alters the composition of cervical mucus, making it impenetrable by sperm. It is believed that blockage of ovulation is the most important mechanism in these pills, and the other mechanisms, if invoked at all, serve to guarantee effectiveness. Obviously, these pills act prior to fertilization, and make it impossible for fertilization to occur. Sequential Pills. These pills are chosen by some in order to provide a more normal menstrual flow, with fewer side effects, and they are less effective than combination pills. They provide only estrogen in the first two weeks, which suppresses the normal mechanism for growth of the ovarian follicle, but lack the specific block to ovulation provided by progestins. The inclusion of progestins in the following 7 days serves no contraceptive purpose; it is designed only to regulate menstrual flow. Again, these pills exert contraceptive effect prior to fertilization, and interfere with follicle development leading to ovulation.

Minipills. These pills contain only a minute amount of progestins, and the dose is too low to effectively block the LH surge, and ovulation. The primary action here is believed to be alteration of the cervical mucus, making it impenetrable by sperm. Consequently, this is actually a barrier method, and again acts prior to ovulation. However, this barrier is not perfect, and pregnancies can rarely

occur.

Postcoital Pills.-The exact mechanism of action of these pills is not known, but the fact that they are effective if administered within 72 hours of sexual intercourse, when this exposure took place at the time of ovulation, suggests that they may act primarily to prevent fertilization. It is known that they do act, directly and indirectly, on the endometrium, or lining of the uterus, making it quite unfavorable for implantation of the fertilized egg. The preparation of the endometrium for implantation relies heavily on progesterone, supplied by the corpus luteum of the ovary, and the manufacture of progesterone is markedly suppressed by postcoital pills. Another action of these pills is to alter tubal and uterine muscular activity, possibly disturbing the time sequence of fertilization. In summary, the mechanisms of action of all contraceptive pills except postcoital pills, are believed to take place before fertilization, while circumstantial evidence suggests that postcoital pills may interfere with implantation, and also may inhibit successful fertilization.

Sterilization as a method of birth control is becoming increasingly popular, and requires little discussion. The various methods, in men and women, are designed to prevent, by surgical interruption, access of sperm to the egg. They are, with current technology, safe, effective, and by design, permanent methods of birth control, acting to prevent fertilization.

STATEMENT OF GORDON W. DOUGLAS, M.D., PROFESSOR OF OBSTETRICS AND GYNECOLOGY, NEW YORK UNIVERSITY SCHOOL OF MEDICINE, NEW YORK, N.Y.

Dr. DOUGLAS. I am Dr. Gordon W. Douglas, professor of obstetrics and gynecology, New York University School of Medicine, New York, N. Y.

Mr. Chairman and members of the subcommittee, I wish to express my appreciation for the opportunity to present testimony on this subject to the subcommittee.

Oral contraceptive pills have been under investigation since 1956, and in approved clinical use since 1960. Today, nearly one-third of women practicing birth control employ this method, and the number of present and former users number in the many millions. As a method, oral contraceptives have been characterized by a very high degree of effectiveness, approaching 100 percent, and by a high degree of safety, substantially greater than pregnancy itself.

Oral contraceptives fall into four major categories, based on the components of the pills and the timing of administration. All contain one or both of two classes of chemical substances, estrogen and progestins, which function in the body as hormones.

First, the combination pills. These contain both estrogen and progestin, and are administered daily for 21 days, with an interruption of 7 days before a new cycle of pill use is begun.

Second, are sequential pills. During the first 14 days, estrogen alone is administered, followed by 7 days of use of a combination of estrogen and progestin. Again, a 7-day interval precedes the beginning of a new cycle of use.

Third are minipills. These contain progestins only, in very small dosage, and are taken continuously.

Fourth are postcoital or morning after pills. These contain only estrogen In high dosage, and are started within 72 hours of sexual intercourse, and continued for 5 days.

These classes of contraceptive pills have different mechanisms of action, which accounts for the very high degree of effectiveness. First, combination pills. In the normal young woman, ovulation coincides with a rapid rise in the blood of lutenizing hormone, or LH, which is released by the pituitary gland. This is known as the LH surge, and without it, ovulation does not occur. The LH surge is effectively blocked by the progestin in these pills, and ovulation does not occur. A second mechanism is exerted by estrogens, which suppress the pituitary hormones responsible for development of the ovarian follicle in which the egg resides. Third, the progestin component alters the composition of cervical mucus, making it impenetrable by sperm. It is believed that blockage of ovulation is the most important mechanism in these pills, and the other mechanisms, if invoked at all, serve to guarantee effectiveness. Obviously, these pills act prior to fertilization, and make it impossible for fertilization to occur.

Sequential pills. These pills are chosen by some in order to provide a more normal menstrual flow, with fewer side effects, and they are less effective than combination pills. They provide only estrogen in the first 2 weeks, which suppresses the normal mechanism for growth of the ovarian follicle, but lack the specific block to ovulation pro

vided by progestins. The inclusion of progestins in the following 7 days serves no contraceptive purpose; it is designed only to regulate menstrual flow. Again, these pills exert contraceptive effect prior to fertilization, and interfere with follicle development leading to ovulation.

Minipills. These pills contain only a minute amount of progestins, and the dose is too low to effectively block the LH surge, and ovulation. The primary action here is believed to be alteration of the cervical mucus, making it impenetrable by sperm. Consequently, this is actually a barrier method, and again acts prior to ovulation. However, this barrier is not perfect, and pregnancies can rarely occur. Postcoital pills. The exact mechanism of actions of these pills is not known, but the fact that they are effective if administered within 72 hours of sexual intercourse, when this exposure took place at the time of ovulation, suggests that they may not act primarily to prevent fertilization. It is known that they do act, directly and indirectly, on the endometrium, or lining of the uterus, making it quite unfavorable for implantation of the fertilized egg. The preparation of the endometrium for implantation relies heavily on progesterone, supplied by the corpus-luteum of the ovary, and the manufacture of progesterone is markedly suppressed by postcoital pills. Another action of these pills is to alter tubal and uterine muscular activity possibly disturbing the time sequence of fertilization.

In summary, the mechanisms of action of all contraceptive pills except postcoital pills, are believed to take place before fertilization, while circumstantial evidence suggests that postcoital pills may interfere with implantation, and also may inhibit successful fertilization. Sterilization as a method of birth control is becoming increasingly popular, and requires little discussion. The various methods, in men and women, are designed to prevent, by surgical interruption, access of sperm to the egg. They are, with current technology, safe, effective, and by design, permanent methods of birth control, acting to prevent fertilization.

Senator BAYH. Thank you very much, Dr. Corfman and Dr. Douglas. I apologize for my tardy arrival. I found difficulty in extracting myself from a meeting involving some very important constituents. I am sorry I kept you waiting. I appreciate the fact that my distinguished colleague from North Dakota got our hearing started this morning.

Dr. Corfman, in your statement you mentioned that the data that you based your conclusions on were the result of a survey of married women and unmarried women. That might not necessarily substantiate this data or the statistics might be different.

Is that a significant factor in looking at the overall effect on the total women population in the country?

Dr. CORFMAN. The data that I presented came from surveys about contraceptive practices done recurrently in this country. Such surveys involve only married women. We have reason to believe that women who are unmarried are more apt to use other methods, particularly the IUD. Many of the women who attend public clinics subsidized by the Department are unmarried and therefore would not be participants in the survey.

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Senator BAYH. Do the public clinics or the health service or some other agency of our Government have the data as far as the population who use public health clinics?

Dr. CORFMAN. Yes. I cannot answer that with expert knowledge, but the Department probably has data on the use of different contraceptive methods in clinics. I suggest that the question be directed to Dr. Louis Hellman, who is the Deputy Assistant Secretary for Population Affairs.

Senator BAYH. Could either or both of you gentlemen give us some more information about the kind of experimental research that is being done with IUD's in animals? I understand some of this is being done as far as humans are concerned.

Could you give us an idea about the strength and weaknesses and the possibility of this particular device continuing or being changed and the accuracy of the results that you feel from the figures?

Dr. CORFMAN. As far as helping us understand how they work? Senator BAYH. Yes, and whether the experiments have been done in animals. What reliability do they have as far as the reaction of the device on humans?

Dr. CORFMAN. I attempted to review that information in my statement. The fact is that we shall probably never know for certain how IUD's work on humans. To start with, we shall never know with complete accuracy how normal reproduction occurs. For example, I doubt if we shall ever actually observe the fertilization process. Such research would be unethical.

We know a very great deal of how IUD's work in animals, and I did mention that they have a wide variety of effects depending on the species.

Senator BAYH. That is why I asked the question about the relationship to the effect they might have on women.

Dr. CORFMAN. The closest animal model is the subhuman primate, the monkey. The conclusion from that work is that IUD's prevent implantation. They may or may not inhibit fertilization. Perhaps Dr. Douglas would like to add to that.

Senator BAYH. If you share each other's views and support one another or if you have differences-very frankly we would like to know because this is one of the key questions, I think.

Dr. DOUGLAS. Our work in this area has been clinical. It has generally been directed toward demonstration of the safety and effectiveness of IUD's in women. We have utilized over the years quite a few different kinds of devices and currently are concerned along two lines. One of them is the mechanism of action along with the effectiveness of intrauterine devices with a copper content or with slowly released progestins contained in the device. These were referred to by Dr. Corfman. It appears that the device itself can be smaller-that it is very well tolerated under these circumstances and the side effects. are quite minimal.

The second area of investigation has to do with the location of these devices in the uterus over considerable periods of time. Currently, recommendations are made for removal and replacement of the devices after 3, 4 or 5 years.

Some of our studies are showing, without much in the way of symptoms, that the device does become at least partially embedded in the wall of the uterus. And this property is different for different kinds of devices.