Third-generation OCs safe, health officials say
The safety of third-generation oral contraceptives (OCs) is being affirmed by health experts around the globe following publication of a research paper showing that Danish hospital admissions for venous thromboembolism have increased 16% since the rise in prescriptions for third-generation pills.1
The British government, moving swiftly to avert a recurrence of what was termed the "pill scare" in 1995, released a statement to reassure women, stating "The risk of thromboembolism with oral contraceptives is very small and the Pill is a very effective method of contraception. Pregnancy itself carries a much greater risk of thromboembolism than using an brand of contraceptive pill."2
[See Contraceptive Technology Update, Janu ary 1996, p. 6, for an overview of the origins of the "pill scare," which arose following a warning from Britain’s Committee on the Safety of Medicines (CSM) on the use of OCs containing gestodene and desogestrel. A firestorm of controversy ensued throughout Europe, which undermined general confidence in the pill.]
The British government’s move comes as the second vote of confidence this year of its beliefs surrounding third-generation oral contraceptives. A review by the Medicines Commission, a British government advisory body, concluded in April that doctors can prescribe these pills as a first-line form of contraception.3 The commission did confirm the CSM’s concerns about increased risk of blood clots in users of third-generation pills. However, it said that as long as women were fully informed of the risks, which were small, the pills could be considered on equal footing with other contraceptive pills.
Look at the study
The just-published study looks at hospital admission rates for venous thromboembolism during the 1980s and the beginning of the 1990s, when use of third-generation OCs increased in Denmark.
According to Lene Mellemkjær, MSc, PhD, lead author of the study and research fellow at the Institute of Cancer Epidemiology in Copen hagen, Denmark, researchers wanted to examine venous thromboembolism risk among users of third-generation OCs in comparison to those using second-generation pills. The scientists also reviewed mortality from venous thromboembolism during that same time period.
"Previous epidemiologic studies4,5,6 showing that risk of venous thromboembolism is higher among users of third-generation oral contraceptives compared to users of second-generation OCs have been criticized for being influenced by bias," observes Mellemkjær. "One proposed bias is that third-generation OCs may to a larger extent have been prescribed to women at high risk of venous thromboembolism, because third-generation OCs were thought to be safer."
If that is indeed the case, there should be no change in the incidence of venous thromboembolism during the time that the use of third-generation OCs increased, the Danish researchers say. This hypothesis is made under the assumption that there was no overall change in the use of OCs and no change in other risk factors for venous thromboembolism or diagnostic procedures, notes Mellemkjær.
"We studied admission rates for venous thromboembolism among Danish women and men at the ages 15 to 49 years during 1977-93 and mor tality rates during 1977-95," says Mellemkjær. "Among women, the admission rates were quite constant through the 1980s but seemed to increase to a higher level in the beginning of the 1990s, whereas the rates among men were quite constant throughout the period. There was no change in the mortality rates for either women or men."
The finding of an increase in the admission rate for venous thromboembolism among women supports the hypothesis that third-generation OCs increase the risk of venous thromboembolism to a larger extent than second-generation pills, but the results should be interpreted with great caution, states Mellemkjær.
"First, our study was a correlational study where we did not look at the individual woman admitted with venous thromboembolism to find out if she had used OCs, so changes in other risk factors or changes in diagnostic procedures may be alternative explanations for the increase in admission rates," Mellemkjær notes. "Secondly, the admission rates are based on small numbers, and the statistical variation of the increase in the admission rates is considerable."
Overall, the amount of information in the study is limited and does not justify any detailed analyses or strong conclusions; it must be viewed in context with the results of all the previous studies on the subject, Mellemkjær concludes.
Staying the course
American providers say their thinking is unchanged when it comes to the safety of third-generation birth control pills.
"Based on the overall evidence, my perspective is that when prescribing OCs formulated with 35 mcg estrogen or less, concerns regarding thromboembolism do not form a basis for preferring a given estrogen dose or progestin type," says Andrew Kaunitz, MD, professor and assistant chair of the OB/GYN department at the University of Florida Health Science Center in Jacksonville.
David Grimes, MD, vice president of bio medical affairs at Family Health International in Research Triangle Park, NC, co-authored a review of the major research surrounding the third-generation pills, which concluded that "modern combined oral contraceptives are safer than earlier formulations with respect to cardiovascular disease, which occurs rarely in young women."7
"All I have to say about the third-generation issue is in [that] review," Grimes comments. "Nothing published since then has changed my assessment."
References
1. Mellemkjær L, Sorensen HT, Dreyer L, et al. Admission for and mortality from primary venous thromboembolism in women of fertile age in Denmark, 1977-95. BMJ 1999; 319: 820-821.
2. BBC. Government plays down fresh pill worry. London, England; Sept. 24, 1999.
3. BBC. U-turn over pill scare. London, England; April 7, 1999.
4. World Health Organisation Collaborative Study on Cardiovascular Disease and Steroid Hormone Contracep tion. Venous thromboembolic disease and combined oral contraceptives: Results of international multicentre case- control study. Lancet 1995; 346:1,575-1,582.
5. Jick H, Jick SS, Gurewich V, et al. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346:1,589-1,593.
6. Spitzer WO, Lewis MA, Heinemann LAJ, et al. Third generation oral contraceptives and risk of venous thromboembolic disorders: An international case-control study. BMJ 1996; 312:83-88.
7. Rosenberg L, Palmer JR, Sands MI, et al. Modern oral contraceptives and cardiovascular disease. Am J Obstet Gynecol 1997; 177:707-715.
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