Third Generation Pill Story
On 4th March 2011 the University of Otago’s department of Preventative & Social Medicine celebrated 125 years Public Health Teaching and Research by hosting a symposium in Dunedin in honour of Professor Sir David Skegg. Lynda Williams attended the symposium and reports on the presentation given by Lianne Parkin, a senior lecturer in Epidemiology in the Department of Preventative and Social Medicine at the University of Otago. Before undertaking training in public health medicine and epidemiology, Lianne worked for several years in general practice and in sexual and reproductive health clinics. She is currently involved in a project which aims to improve post-marketing surveillance of medicine safety in New Zealand.
Lianne Parkin’s presentation at the Dunedin symposium described the events surrounding the use of the third generation contraceptive pill in New Zealand.
In 1995 following the publication of three European studies showing that there was an increased risk of venous thromboembolism (blood clots) in women using third generation contraceptive pills, a warning was issued about the safety of four brands of these contraceptive pills – Minulet, Mercilon, Marvelon, and Femodene.
The risk of blood clots for third generation contraceptive pills which contain gestodene as well as oestrogen, was estimated to around twice that of second generation pills. Although the risks of blood clots for both are comparatively low, the sudden deaths of healthy young women created a great deal of publicity both in New Zealand and in other countries. In New Zealand in 1995 80% of oral contraceptive pill users were taking a third generation contraceptive pill, the highest percentage in the world. The Netherlands the figure was 63%, in the UK 50%, in both Canada and the USA 15%, and in Australia 5%.
Following the publication of the European studies, an urgent meeting was convened in Geneva in July 1995. A vast amount of reanalysis of the data was subsequently undertaken, mainly by the pharmaceutical industry and by pharmaceutical-industry sponsored groups. Eventually, independent research confirmed the original results.
When the story of the increased risk broke the Ministry of Health sent out a warning to doctors, but then withdrew it a week later. Once the results of the reanalysis were available, the MOH sent out new information that basically said that it was not necessary to alter prescribing advice if women are told of the risks in using third generation contraceptive pills. Not surprisingly, the Ministry’s prescribing advice had minimal impact on doctors' prescribing practice. The Medicines Adverse Reactions Committee (MARC) objected to such a low key approach, as did a number of women’s groups.
In May 2000 a letter from the Royal Australia and New Zealand College of Obstetricians and Gynaecologists was published in the NZ Medical Journal maintaining that there was no difference between the second generation and third generation pills. An article by Christine Roke from Family Planning and Paul Egermayer was also published in New Ethicals Journal in January 2000. The letter and article were criticised as being misleading and inaccurate as both misrepresented the research data.1
Professor David Skegg commented at the time: “The debate on third generation oral contraceptives has been acrimonious, partly because it has challenged both strong commercial interests and the natural reluctance of prescribers to accept that trusted products have potentially done harm.”
20 healthy young women died
The MOH subsequently released figures that showed in the decade between 1990 – 2001, 20 NZ women using combined contraceptive pills died of a blood clot in the lungs. Of those who died, 15 were using third generation pills. Five of those deaths occurred in the years 1997/1998. Many other women suffered a blood clot and survived, although with a vastly reduced quality of life. By 2001 the use of third generation pills in NZ had more than halved.
Unfortunately the story doesn’t end there. A recent study published in the British Medical Journal in April 2011 showed that women using Yasmin, an oral contraceptive pill containing drospirenone (a new progestogen) were about three times more likely to develop blood clots. Concerns about this pill have been around for almost a decade.2 But once again the pharmaceutical industry - in this instance, Bayer - has been reluctant to admit that their "new" oral contraceptive pill containing drospirenone carried almost three times the risk of blood clots than the second generation contraceptive pills containing the older form of progestogen. The much touted reduced side effects with Yasmin have also turned out to be little more than a marketing ploy. And once again healthy young women have paid with their lives.
1. Letter to New Zealand doctors, midwives and pharmacists about third generation oral contraceptive pills - June 2000
2. Parkin, L, Sharples, K, Hernandez, RK, and Jick SS, 2011, Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database. BMJ, Apr 21;342:d2139.