By, Paul Candon, Medical Tribune News Service
So-called ``third generation'' oral contraceptive pills, the
most recent ones developed, may cause more potentially dangerous
blood clots than with older pills, researchers in Denmark say.
The third-generation pills, first marketed in Denmark in 1984,
have a different form of the progestin hormone and have been
promoted by the pharmaceutical companies that market them as less
likely to contribute to heart disease than ``second-generation''
pills.
Oral contraceptive pills usually contain either a combination of
progestin and estrogen or progestin alone. In recent years,
physicians have prescribed the newer pills more frequently. In
1984, third-generation pills constituted only 0.2 percent of all
oral contraceptive prescriptions written by Danish physicians. This
increased to 17 percent in 1988 and to 66 percent in 1993.
Progestins in third-generation birth control pills include
desogestrel, gestodene and norgestimate. Progestins in
second-generation pills include levonorgestrel.
In a report published in the September 25 edition of the British
Medical Journal, investigators analyzed Denmark's records for
hospital admissions and deaths due to various blood clot disorders
in people ages 15 to 49. When use of third generation pills
increased sharply, between 1989-1993, women's admission rate for
the blood clot disorder thromboembolism was 16 percent higher than
when second generation pills were most commonly used, between 1977
and 1988. Admission rates for men did not change.
The increase is probably not the result of any change in the way
physicians diagnose the condition, the researchers wrote. Nor is it
likely the result of simply more people seeking help for the
condition, because the rates for men stayed the same. The research
team was led by Lene Mellemkjr, a research fellow at the Danish
Cancer Society in Copenhagen.
Thromboembolism involves the formation of blood clots, usually
in the legs, that can cause circulation problems and swelling.
These blood clots can dislodge and subsequently block blood flow to
the lungs, a potentially fatal condition.
Factors that may predispose women to developing dangerous blood
clots with contraceptive use include a history of thromboembolism,
obesity, circulatory difficulties or a family history of such
problems. Other risk factors for thromboembolism are varicose
veins, recent surgery or cancer diagnosis.
In 1998, the American College of Obstetricians and Gynecologists
in Washington, D.C., reported that for every 100,000 women taking
third generation pills, 20 to 30 will develop nonfatal blood clots.
This is almost double the rate of 10 to 15 per 100,000 with second
generation pills. In women who are not pregnant, the rate is 4 per
100,000; in pregnant women, it is 60 per 100,000.
Dr. Robert Hagler, chairman of the Gynecologist Practice
Committee for the American College of Obstetricians and
Gynecologists, said in an interview that he routinely prescribes
second generation pills ``unless I have patients who can't tolerate
them or who have problems. Then I will go to a third generation
pill.''
Hagler pointed out that the second generation pills may be
safer, especially in light of this new report. ``But also,'' he
said, ``they do what we need them to do: They provide good
contraception, good cycle control, and so they work very well.''
The evidence from this and previous studies ``indicates that
second generation contraceptives should be the first choice,''
wrote Paul O'Brien in an editorial that accompanied the article.
O'Brien is a senior medical officer in clinical effectiveness at
St. Charles Hospital in London. He noted that the past studies had
received ``relentless criticism,'' for flaws in research design. In
a $3 billion world contraceptive market, he wrote, ``the stakes are
high.''
``Opinion is still divided on whether or not the effect is
real,'' said Dr. David Grimes, vice president of biomedical affairs
at Family Health International in Research Triangle Park, N.C. ``I
am inclined to believe that most, if not all of the effect, is due
to bias.'' The increased incidence of clots that most studies have
found, he said, is almost imperceptible in statistical terms. ``The
risk of having a clot in a healthy young woman is so remote, and
they're so rarely fatal, that the net public health impact is
really quite small.''
Grimes pointed out that the risk of having a clot is still much
smaller for women taking third generation pills than for those who
are pregnant. ``We've seen a flurry of press attention surrounding
this issue, which has had a negative effect on women's health by
casting a shadow'' over all contraceptive pill use, he said. ``And
today's pills, whether they be second or third generation, are very
safe.''
