For five months, physicians who prescribe birth-control pills for millions of women have been getting a comprehensive new set of prescribing instructions - the result of the first government overhaul of the official labeling since 1968 to reflect a host of newly established risks.
But the consumer - the woman who takes the pill - continues to find in each package a terse, 150-word advisory leaflet derived from the now-discarded 1968 physician labeling.
The Food and Drug Administration says that the user leaflet, which it first required in 1970, is not only out of date, but also grossly inadequate for the woman who wants to inform herself about the relative safety and effectiveness of the pill and other forms of contraception.
Eventually - maybe within months - the FDA will replace the obsolete user leaflet with a "Brief Summary Patient Package Insert," with an extensive, detailed brochure, "What You Should Know About Oral Contraceptives." Doctors and pharmacists will be required to provide a copy of the brochure each time a prescription for the pill is written or refilled.
Both the insert and the brochure - written in language notably free of technical jargon - will faithfully reflect the overhauled labeling for doctors, which manufacturers, under FDA order, have been providing to the medical profession since April 6.
The agency published a draft or proposed version of the "What You Should Know . . ." user brochure Dec. 7 in the Federal Register, a government publication in which agencies serve formal notice of plans to change their regulations. Members of the public rarely see it.
The purpose was to invite comments from anyone who cared to file them, including manufacturers, physician organizations, consumer groups and the public.
Eight months later, after the comments that came in had been considered, a draft final version is circulating among FDA officials. But a spokesman says he cannot predict how much longer it will be before a "final final" version starts to be routinely supplied to consumers.
Chances are, the spokesman says, that the draft published in December is very close to what the final brochure will be.
And, he says, anyone who wants a copy of the draft can have one by writing to: Consumer Inquiries Unit, HFG-20, Food and Drug Administration, 5600 Fishers Lane, Rockville, Md. 20857.
"It is important that any woman who considers using an order contraceptive understand the risks involved," the draft brochure says. "Only you can decide whether the advantages are worth risks."
The brochure lists women who should not use the pill, including those who had a blood clot in a leg or lung, a heart attack, a stroke, angina pectoris, known or suspected breast or genital cancer or unusual and still-undiagnosed vaginal bleeding.
Another section of the text lists signals to which a user should be alert, so that she can call her doctor if any occurs.
The signals include sharp chest pain, coughing blood, or shortness of breath - each indicating the possibility of heart attack. Other signals:
"Pain in the calf (possible clot in the leg).
"Crushing chest pain or heaviness (indicating possible heart attack).
"Sudden severe headache or vomiting, dizziness or fainting, disturbance of vision or speech, or weakness or numbness in an arm or leg (indicating a possible stroke).
"Breast lumps . . .
"Severe pain in the abdomen (indicating a possible ruptured tumor of the liver).
"Yellowing of the skin (jaundice)."
Another section compares the effectiveness of various methods in preventing pregnancy, but the FDA has revised the data in the Federal Register draft in favor of the following, all figured on the basis of pregnancies - or failure rate - per 100 women per year:
The pill is extremely effective, with the exact failure rate depending on the formulation. For formulations containing 20 to 35 micrograms of estrogen, the number of pregnancies per 100 users per year is put by the FDA at less than 1 to 2. For formulations containing only a progestin, the number of failures is calculated at about 3.
For other methods, the figures are:
Intrauterine device (IUD), less than 1 to 6; condom (rubber), 3 to 36; diaphragm with spermicidal products, 2 to 20; aerosol foams, 2 to 29, and jellies and creams, 4 to 36.
For rhythm, the brochure gives the following pregnancy rates, also per 100 women per year: calendar method, 14 to 47; temperature method, 1 to 20; temperature method with intercourse only in post-ovulation phase, less than 1 to 7, and mucous methoud, 1 to 25.
The FDA says that with no contraception, the rate ranges between 60 and 80.
Another key part of the brochure is a bar graph that combines various studies to estimate the death risk in nonsterile women on the pill (because of abnormal clotting) and on other forms of conception control (because of pregnancy or abortion in the event the method fails).
The graph deals separately with six age groups in the child-bearing range of 15 through 44. In the 30-to-34 age bracket, for example, the annual death rate per 100,000 is about 5.2 for either, the pill or abortion, about 1.2 for the IUD, about 3.5 for the condom or diaphragm, and about 0.8 for such traditional contraception plus abortion.With no countraception, deaths number 14.
Summing up the graph, the text says it "shows that the risk of death from all methods of birth control is low compared to the risks of child EXCEPT FOR ORAL CONTRACEPTIVES IN WOMEN OVER 40." In women 40 to 44, the graph shows, deaths on the pill number 25, compared with, say, 1.2 for the IUD.
The text adds that the data show "that the lowest risk of death is associated with the condom or diaphragm (traditional contraception) backed up by early abortion in case of failure of the condom or diaphragm to prevent pregnancy."
The brochure contains information on how the pill is believed to work, dosages, the risks of clotting and heart attack, elevated blood pressure, gall bladdar disease and other adverse effects.
"No proof exists at present that oral contraceptives cause cancer in humans," the draft says, "but it remains possible they will be discovered in the future to do so."
The first pill, G. D. Searle & Co.'s Enovid in an early formulation, went on sale in 1960. For the following eight years, the FDA and each of an increasing number of suppliers negotiated official labelings separately for the various brands.
The process was something like collective bargaining between a company and a union, although the purpose was to instruct physicians purely on the basis of scientific facts.
The results were sometimes bizarre. Consider the pill formulation consisting of specified amounts of the hormones norethindrone and mestranol.
The labeling for the Norinyl brand admonished that it should not be prescribed for women with a history of psychic depression "if depression recurs to a marked degree."
Another company sold the same formulation as Ortho-Novum. But the label for this brand did not carry the same admonishment about depression. Instead, there was a mild suggestion in the "precautions" section that patients with a history of depression be "carefully observed."
Inconsistencies of this sort were doomed in the mid-1960s by pioneering British studies that established that in some users the pill - regardless of formulation or brand - caused blood-clotting diseases, particularly thrombophlebitis and thromboembolism.
In June, 1968, the FDA put into effect a uniform label for all manufacturers and brands. Even so, a few anomalies persisted.
For example, the new label cast a shadow over the relevance of the British studies for American women by saying that data on British women "cannot be directly applied to women in other countries . . ." But no implication of irrelevance to American women was made for the early studies purporting to establish the pill's safety even though those studies were done in Haiti and Puerto Rico.
More importantly, the British studies established a clear cause-effect relationship between the pill and bloodclotting diseases, which sometimes are lifelong disabling or fatal. The FDA staff draft for the 1968 label said precisely that. But the final version blurred and softened the warning, partly by substituting "a statistically significant association" for the proposed "cause-and-effect relationship."
According to sworn courtroom testimony by Dr. Robert S. McCleery, a former FDA official, the shadow on the British studies and the deletion of "cause effect relationship" resulted from pressure applied on the agency by pill manufacturers at a meeting in May, 1968.
By 1977, the pill had been used in the United States, for varying periods of time, by an estimated 35 million women. How many were influenced to do so by the softened labeling directly or through their physicians, is unknown.
Meanwhile, one scientific study after another - dozens, in all - implicated or incriminated the pill in a variety of afflictions for which there had been inadequate or no evidence when the 1968 prescribing instructions were adopted. The pill, Dr. Herbert Ratner, an early critic, has said, "is certainly the most talented drug ever introduced in its ability to produce diverse and varied disease phenomena and systematic abnormalities in normal women."
One of the most startling developments came early last year, when the FDA forced the removal of so-called sequential oral contraceptives, then being taken by up to 1 million women, because of womb cancer. A woman on a sequential regimen took estrogen - only tablets for part of the menstrual cycle and estrogen-progestogen combination tablets for the rest of the cycle. Most brands are combinations taken 20 or 21 days of each cycle.
Another highly disturbing development came in May, 1975, when British scientists reported studies showing that the risk of heart attacks in pill users increased with age, to a point that the FDA recommended alternative forms of contraception in women 40 and older.
Five months later, however, a biostatistician for the Population Council in New York City, Anrudh K. Jain, disclosed in a telephone interview that a tentative analysis showed the heart attack hazard in pill users to the mainly in cigarette smokers.
Last March, when Jain completed the analysis, he said that it is the combination of pill use and heavy smoking that is likely to precipitate heart attacks, particularly, but not entirely, in women over 30.