Desogen

An increased rate of blood clots is associated with the latest version of oral contraceptives (OCs). In October, the finding, which was consistent in three studies, was announced in the British media prior to publication. The alert issued by the British version of the FDA unleashed a fury among doctors there who did not like hearing the news at the same time as their patients. No similar announcement has been made in this country, though one of the new studies was conducted here.

All three studies found an increased risk of non-fatal venous thromboembolism (deep vein blood clots) associated with combined OCs containing desogestrel or gestodene, as compared with older brands that combine other synthetic versions of progestin with estrogen. Desogestrel and gestodene are the newest forms of progestin; they are found in the third generation of OCs, that is, the latest version of the birth control pill. (See HealthFacts, September 1995.) The amount of estrogen in OCs has been decreasing over the years, but the amount of progestin is increasing.

Two Brands Sold Here

Third-generation OCs are more widely prescribed in other countries; only two brands, Desogen and Ortho-Cept, are available in the U.S. Both contain desogestrel, which is progestin synthesized from a precursor extracted from wild yams found in Mexico. (Yet another example of a folk remedy turned drug.) When approved by the FDA in 1993, desogestrel was hailed as an improvement over the older versions of progestin because it has fewer androgenic (masculinizing) effects, such as acne, hirsutism (excessive body and facial hair), and weight gain. According to The Medical Letter (6 August 1993), desogestrel-containing OCs also have a lower incidence of other side effects, such as headache, nausea, breast tenderness, and breakthrough bleeding.

But as usual with a new drug, the long-term effects are not known until it has been on the market for years. One of the three new studies of these third-generation OCs was conducted by the World Health Organization. A WHO press release stated that women taking a brand containing either desogestrel or gestodene had twice the rate of thromboembolism as women on other brands that combine low-dose estrogen with levonorgestrel or norethindrone (The Lancet, 28 October 1995).

The impact of this finding, however, has been obscured by the reaction of British physicians, which has been somewhat patronizing. Several charged that the public announcement will cause unwanted pregnancies because worried women will stop taking their pills. In fact, the alert from the Committee on the Safety of Medicine advised women to complete their current cycle and consider switching brands. (Over 50 brands are available in the U.S.) But several prominent physicians judged the finding to be preliminary, thus implying it was not worthy of any action. Some experts argued that any risk of third-generation OCs would be offset by their documented beneficial effect on blood lipids (e.g., cholesterol); this in turn may reduce the rate of heart attacks. Several emphasized that the type of blood clots found in the three new studies were non-fatal.

Letter Leaked To Press

In a recent letter to the British Medical Journal, Professor Michael Rawlins, chairman of the Committee on the Safety of Medicine (CSN), defended its decision to issue the alert and the circumstances that made its announcement somewhat premature. The CSM had planned the alert to follow doctor notification, but its dear doctor letter was leaked to the press.

Professor Rawlins denied that the findings are preliminary. Two of the three studies have been submitted for publication, which means they are going through the process of peer review required by scientific journals. Furthermore, the CSM itself functions as a peer review process.

He contends that there is uncertainty about whether the beneficial effect on blood lipids would translate into fewer heart attacks and strokes for third-generation OC users. It would take years to learn this. As for the decision to go public with the bad news: The CSM would be failing in its duty to the profession and the public if it did not communicate important drug safety information promptly, wrote Professor Rawlins. It will continue to do so. Non-fatal blood clots can produce serious injury; a clot in the eye, for example, could result in the loss of the eyeball.

U.S. Reaction

What has been the reaction to all this in the U.S. where third-generation OCs represent 15% of the market? The American College of Obstetricians and Gynecologists (ACOG) issued a statement at the end of October. It called the data preliminary and suggested waiting for publication and the peer review process it entails for a fuller picture of the safety of third-generation OCs.

ACOG does not recommend that women change their brand of pills, nor does the American Medical Association whose spokesman said it defers to ACOG on this issue. But neither professional organization can be regarded as unbiased. Ortho Pharmaceutical Corporation, the manufacturer of Ortho-Cept, a third-generation OC, has provided ACOG with grants to fund educational activities promoting the safety of OCs. And the AMA's day-long press briefing on women's reproductive health held earlier this year in a New York City hotel was underwritten by Ortho. ACOG spokesman, Dr. Stanley Zimberg, became audibly apoplectic when asked in a recent telephone interview whether receiving grants from Ortho might cloud ACOG's judgment on the question of whether the new findings call for women on Orthoc-Cept to rethink their birth control choice. He refused to discuss the possibility that ACOG's decision could even appear to be compromised by Ortho funding.

The FDA issued its statement on November 14th, downplaying the risk as rare and non-fatal. The FDA has concluded from its review of the three recent unpublished studies that the risk is not great enough to justify switching to other products.

The FDA statement gave the annual odds of non-fatal venous thromboembolism:

four cases per 100,000 in healthy women who are not pregnant and not taking hormones;

10-15 per 100,000 for women taking older, low-dose OCs;

20-30 per 100,000 for women taking desogestrel and gestodene containing products;

60 per 100,000 women for pregnant women.

The FDA statement neglects to mention that the options do not just include pregnancy or other brands of OCs. There are other non-drug birth control methods, such as the cervical cap or the diaphragm, which can be used instead.

COPYRIGHT 1995 Center for Medical Consumers, Inc.
COPYRIGHT 2004 Gale Group