The Pills: More Effective, And More of Them

Last week, with newly announced approval by the Food and Drug Administration of three more oral contraceptives, American women and their doctors had a total of six to choose from.

By federal law, all are available on prescription only. They are:

> Enovid, the longest on the market, made by Chicago's G. D. Searle & Co. in large-dose tablets.

> Enovid-E, just released, a miniaturized version of Enovid.

> Ortho-Novum (Johnson & Johnson's subsidiary, Ortho Pharmaceutical Corp.), on the market since 1962 in a full-dose tablet.

> Ortho-Novum-2, a reduced-dose form on sale since last fall.

-- Norlestrin (Detroit's Parke, Davis & Co.), a new, small-dose tablet. >Norinyl (Syntex Laboratories, Inc.), another new, small-dose pill.

Sales of the pills have been increasing steadily around the world, and especially in the U.S., where the cost (about $4 for a month's supply of the larger pills, $2.25 for the smaller) is less of a deterrent. But as with all new and potent drugs, many questions arise: Just what are the pills? How do they work? Are they certain? Are they safe? What are the disadvantages and discomforts of using them? How long can a woman go on taking them? Could they cause cancer or deform babies in the womb?

The answers, in nearly every case, are reassuring.

Giant Yams. A woman of childbearing age has a menstrual cycle of 23 to 39 days, but the average is close to 28 days, and this figure is always used by doctors prescribing the pills. It is a safe choice because even women who have had different cycles usually convert to a 28-day cycle while on the pills.

Within five days after her cycle starts (see chart), a woman's pituitary gland begins producing the follicle-stimulating hormone FSH, which travels through the blood to the ovaries, which contain about 300,000 follicles. FSH starts a few of these on a growth process that results in the production of one ovum (egg). Around the 14th day of the cycle, ovulation occurs: the follicle releases the ovum, which travels down the Fallopian tube toward the uterus. If it encounters a live spermatozoon on the way, or soon after its arrival, the ovum will be fertilized.

Nature has an automatic regulator to prevent the too-rapid production of another, regardless of whether the ovum is fertilized or not, which might lead to overlapping pregnancies. After any one ovum is released, the body starts producing progesterone. Sometimes called "nature's contraceptive," this hormone serves mainly to prevent the ripening of another ovum until the next cycle starts.

The natural progesterone secreted in women's glands is not very potent when taken by mouth. But since 1951, laboratory experts have been making chemically related substances, now known as progestins, from such unlikely raw materials as the root of the Mexican giant yam. Some of these synthetics are far more potent than natural progesterone--at least for preventing ovulation. The two best known are norethynodrel, the main ingredient in Enovid, and norethindrone, used in the other contraceptive pills now marketed in the U.S. and by various manufacturers around the world.

Uncertain Women. The pills work, in effect, by fooling the body into behaving as though ovulation has taken place when it actually has not. On the fifth day of her cycle, when a woman's system would normally be building up hormones to promote ovulation, she takes the first of her progestin pills, and she takes one daily for the next 20 or 21 days. By some biochemical magic not yet understood, the progestin makes it impossible for a follicle to ripen and spill out an ovum. It also prepares the lining of the uterus for menstruation. By the 25th or 26th day, when all chance of ovulation, and therefore of conception, during that cycle has passed, the woman stops taking her pills. Within two or three days, the on set of menstruation signals the start of another cycle.

"The pills are certain," says one manufacturer flatly. "It is women who are not." Since the first tests began in 1956 there have been sporadic reports that a woman conceived while on the pills, but in virtually every case it was shown that she had missed one or more doses.

The pills are supposed to be taken every 24 hours. If a woman forgets to take hers at the usually recommended dinner hour, she has about twelve hours of grace; most authorities agree that she will be protected if she goes pill-less for no more than 36 hours.

About one out of every four women complains that the pills upset her when she starts taking them. The most common symptoms are nausea (similar to "morning sickness"), a bloated feeling, weight gain, tenderness of the breasts. In most cases, these complaints subside after two or three months. The proportion of women who dropped the pills because of side effects was greater at first, when doses were relatively heavy. Now that dosage has been cut, side effects are fewer.

No Proof. The only serious side effect that responsible medical men have charged against the pills is that they may increase the risk of thrombophlebitis--formation of blood clots, usually in leg veins. A number of women have died of clotting disorders while taking Enovid, but a special committee of experts named by the FDA could find no proof that Enovid was to blame. Many women who have never taken the pills, and who rarely take any drugs, suffer from thrombophlebitis. But nobody knows how the number of such cases compares with that among women taking Enovid. The committee of experts concluded that the pills carry no added risk for healthy women up to age 35, or perhaps 40. For women over 40, the experts are collecting more data. As long as this question remains undecided, no woman who has, or ever has had, clotting difficulties or phlebitis should take the pills.

Can the pills cause cancer? Medical purists argue that no one can be certain for 30 years or so. But present evidence from almost eight years' experience indicates that the answer is likely to be no. There are even a few shreds of hopeful evidence that cancer of the cervix and womb may be less common among women taking the pills.

The vast majority of women who take the pills do not want to be made infertile; they merely wish to space their pregnancies and control the number of their children. Almost invariably they ask: "If I take the pills for a couple of years, and then stop, will I be able to conceive?" The answer is an emphatic yes. By a sort of rebound effect, the pills increase fertility in women who stop taking them. Indeed, the pills were largely developed by a Roman Catholic gynecologist, Boston's Dr. John Rock, working with Biologist Gregory

Pincus to overcome infertility caused by disturbed menstrual cycles. It was only after they found that the pills, taken on a regular schedule for three months and then stopped, seemed to stimulate fertility, that the medical researchers began to try them solely for contraception.

The length of time that a woman can continue taking the pills safely is still uncertain. FDA has set the recommended limit for Enovid and Ortho-Novum at four years, and of Enovid-E at three years, though it is holding the newest pills to two years for the present. There has been some speculation that long-term use of the pills might postpone the menopause and leave women fertile far beyond nature's normal age limit of 45 to 50. But women who were nearing the menopause when they started on the pills several years ago have since had the change of life normal for their age.

Split Schedule. All the oral contraceptives so far approved by FDA contain, in addition to their principal ingredient of the synthetic, progestin, a minute amount of another synthetic hormone, estrogen. This fulfills some of the roles of the estrogen that a woman normally secretes generously during the first part of her menstrual cycle, and it serves to prevent spotting or break-through bleeding in the middle part of the cycle.

Soon, the oral-contraceptive market will be crammed with pills from more manufacturers, some of them to be taken on a divided schedule called "sequential therapy." This system requires taking an estrogen pill for 16 days, then a progestin pill for five days. Its proponents claim that it comes closer to the natural physiological hormone cycle. Mead, Johnson & Co. already has an application before FDA asking approval of sequential-therapy pills compounded of ingredients bought from British Drug Houses, Ltd. And Indianapolis' Eli Lilly & Co., working with Syntex, is on the same tack. Michigan's Upjohn Co. is preparing a pill it calls Provest, and Pennsylvania's Wyeth Laboratories are testing still another.

Nobody knows just how many women are "on the pills," because manufacturers keep sales figures secret. Searle estimated at the turn of the year that 1,600,000 women were taking Enovid for contraception, and the company is now manufacturing 3,000,000 pills a day. All told, the number of U.S. women using them is probably edging toward 3,000,000. And the manufacturers are almost certainly right in their calculation that the market will continue to grow. Dr. Edris Rice-Wray, one of the original investigators, first in Puerto Rico and now in Mexico, says: "It's extremely rare to find a woman willing to accept another method once she knows that 'the pills' exist. Even the poorest, with little or no schooling, are found to be faithful and conscientious users."

This file is automatically generated by a robot program, so reader's discretion is required.