Quinacrine: the non-surgical sterilisation method that refuses to die

16/01/2016 § Leave a comment

A response to all the articles on so-called “permanent contraception” in Contraception 2015;92(2):89-176)

It is with a deep sigh, after more than 10 years, that I sit down to respond to your articles on “permanent contraception”, particularly the one by Jack Lippes pushing quinacrine sterilisation, that dead letter, to the fore once again, in your August journal issue (Contraception 2015;92(2):89-176).

Dr Lippes whitewashes the history of why quinacrine was rejected as a female sterilisation method,[1] rejected not only because of concerns about its carcinogenic potential but for many other reasons as well. Dr Jaime Zipper from Chile, who invented the method, would never be allowed today to get away with the “research” he carried out on women with quinacrine for tubal sterilisation in the absence of any pre-testing of the drug for safety, dosage or efficiacy ‒ before it was ever injected into a single woman. Women were treated like guinea pigs in his and other “research”, and no proper long-term work on safety or optimal dosage was ever completed. Not was the method in fact ever properly approved or registered in any country. There were only a handful of countries where quinacrine sterilisation was ever used, and even in those cases, it was always individual doctors who used it, while others carried suitcases full of quinacrine pellets across borders to share with them, e.g. in a remote rural area of India.

The early high failure rates Dr Lippes reports of 9-12% were indicative of the absence of proper research, since they should have led to a rejection of the method early on. The far lower failure rates shown in the studies in his Table 1 were all from very small studies except for one; most had too short follow-up periods and the findings were never confirmed in larger randomised, controlled studies. The very large study by Dr Do Trong Hieu of Viet Nam, published in the Lancet, in which over 30,000 women were subjected to the procedure, led to the closure of the programme in Viet Nam following a critical analysis of its findings. I was personally involved in creating an outcry about it at that time. (I will return to this below.)

The dismissal by Dr Lippes of the data on cancer risk arising from inflammation in rats, and indeed his whole article, is an example of how the proponents of quinacrine did then and continue to minimise the negative evidence and exaggerate the positive evidence to claim the method is safe.

Dr Lippes’s review of the literature ignores several articles I published in the early days of Reproductive Health Matters (RHM) and one in the BMJ almost ten years later. In 1993 in RHM, Amy Pollack and Charles Carignan[2] examined the same evidence examined in Contraception by Lippes. They noted, for example, that in the Viet Nam paper, 20,000 of the 31,000 women in the total study sample were excluded from follow-up for pregnancy rates, and the finding in one province of 91 pregnancies out of 937 women was also excluded. A year after their article was published, concern was expressed by Ralph Heywood, consultant toxicologist to WHO in 1994,[3] that more research needed to be done to exclude toxicological effects related to mutagenicity, teratology and persistence of the compound in tissues. He recommended that toxicological testing of quinacrine in animals should be done prior to any further clinical trials or any other provision of the method to women.3 Dr Lisa Rarick, the then Medical Officer at USFDA, also raised concerns, given the uncertain failure rate, that a quinacrine failure might increase the risk of ectopic pregnancy.3 Yet despite this published concern, a number of individual doctors continued to promote and perform quinacrine sterilisations ‒ e.g. in rural India and Pakistan. I asked what should be done when consensus views are ignored or rejected by individual providers. The question still holds. A year later, and following a further statement on toxicity and quinacrine by Ralph Heywood,[4] quinacrine sterilisations were still being done in Chile too, led by Dr Jaime Zipper, but challenged by the Foro Abierto de Salud y Derechos Reproductivos (Open Forum for Reproductive Health and Rights).[5] It was this and other feminist activism that led to the decision by WHO not to recommend quinacrine sterilisation of women to be continued, until far more rigorous examination of safety and efficacy was carried out.

But the problem of promotion of untested methods remains with us. In 2004, the BMJ published an article about a “clinical trial” in India evaluating the antibiotic erythromycin as a female sterilisation method,[6] following the ban by India on the use of quinacrine for that use, due to safety and efficacy doubts. Quinacrine’s dwindling supporters were looking for an alternative. They tried erythromycin tablets, which were placed in the upper part of the uterine cavity in 790 women “volunteers”. The failure rate was unacceptably high at 28–35% after 12 months. This “trial” was criticised as illegal and unethical, and highlighted the ease with which unethical clinical trials could still be conducted in India on vulnerable populations by errant doctors.

The FHI360 article was a real eye-opener for me, as it seems they were responsible for the erythromicin study in India, which I do not recall. It is not surprising, however, as FHI was a driving force in this whole history. The history revealed in this article is indicative of the determination not to let this idea go, and even to bring unnamed advocates on board to try and legitimise what could not be justified.[7]

Turning to the other articles on the subject of non-surgical sterilisation in your August edition, I was interested to see how the article by Elizabeth K Harrington et al[8] quietly denigrated the whole idea of surgical sterilisation because it is surgical, in that it requires training and a decent service delivery setting. Is training and a decent service delivery setting still not a reasonable expectation for women in the global South? She is right, not everyone prefers a surgical method. Yet she admits that surgical female sterilisation has not only been shown to be very safe but is also the most widely used fertility control method globally.

Interestingly, none of these articles takes up the alternative of vasectomy ‒ an unfinished job if ever there was one ‒ let alone the idea of a permanent non-surgical male method. Odd that no one has tried inserting quinacrine in men’s nether parts, or is it? The biases may not seem obvious in the absence of a thorough review of the issues, but bias there is indeed among the cluster of authors who populate this whole journal edition.

The comparison I felt was most relevant and most missing in these papers, however, was that between surgical vs. medical abortion, the only existing surgical and non-surgical methods of fertility control. Both these abortion methods are easy to provide in the first trimester of pregnancy, and both have been shown by WHO to be safe for mid-level providers to offer at primary care level, with simple training.[9] Both have advantages as well as disadvantages, but the real value is that women have a choice between them.

My generation put the notion of “choice” in fertility control on the global map and showed that the more and varied methods there were to choose from, the more people were likely to find at least one method that was acceptable and met their needs. Your authors in this edition have quite a different perspective. They want something that will end fertility, and the less likely it is to “fail” or “fail to be used” the better. From this position, Elizabeth Harrington et al3 and Jeffrey Jensen[10] seem to assume that a long-acting method of contraception is always preferable to the others. This has not been shown, nor is it likely to be true ‒ if one asks a large enough number of women and their partners, and especially young people. And in spite of the still rising numbers of people with HIV and other sexually transmitted infections, the importance of condoms seems to have passed these authors by altogether. In fact, both qualitative studies by Elizabeth Harrington et al3,[11] find the demand for safety to be uppermost as a value among study participants. Moreover the preference expressed for a non-surgical sterilisation method is hypothetical and with caveats ‒ and not based on the experience of surgical sterilisation or an actual non-surgical method.

I would also question these authors’ preference for the term “permanent contraception” rather than “sterilisation” and “vasectomy”. Both these surgical methods can be reversed, and although Jeffrey Jensen likes to think women’s fertility intentions fall rigidly into only three categories, there are quite a few people who have opted for sterilisation or vasectomy who have later changed their minds, and for whom reversal methods were consequently developed. To use the term “permanent” belies that availability, and might even put people off. It would certainly mislead them into thinking there is no going back. Perhaps that is what the supporters of quinacrine sterilisation are aiming for. They seem not to have considered that the lack of potential for reversal with quinacrine might greatly decrease its appeal, even among those for whom “something non-surgical” may be preferable. Of course, no one has attempted to reverse a quinacrine sterilisation. Once the fallopian tissue is thus scarred, it is presumably very permanent indeed.

Lastly, I must say that for a journal that publishes first class research on abortion, I was very disappointed to see you allowing remarks about the need for abortion as a sign of failure ‒ whether of contraceptive methods themselves or of the women who choose them. Can we not finally acknowledge contraception as a fallible form of prevention and abortion as a solution when prevention fails? The belief that contraception which never fails is possible is, in my view, a chimera. Moreover, if women were given proper information and unrestricted access to safe abortion methods, most abortions would take place well before 8 weeks LMP, and even (with medical abortion) as early as 35 days of pregnancy (Beverly Winikoff, personal communication, July 2015). Let’s try developing new non-surgical post-fertilisation methods of birth control, for example.[12]

However, whether or not one thinks a non-surgical method of sterilisation would be preferable to a surgical method, quinacrine is not the answer. Let’s re-bury it and keep it buried.

References

[1] Lippes J. Quinacrine sterilization (QS): time for reconsideration. Contraception 2015;92(2):91-95. http://www.sciencedirect.com/science/article/pii/S0010782415002322.

[2] Pollack AE, Carignan C. The use of quinacrine pellets for non-surgical female sterilisation. Reproductive Health Matters 1993;1(2):119-22. http://www.rhm-elsevier.com/article/0968-8080(93)90018-O/pdf

[3] Berer M. The quinacrine controversy one year on. Reproductive Health Matters 1994;2(4):99-106. http://www.rhm-elsevier.com/article/0968-8080(94)90016-7/pdf.

[4] Berer M. The quinacrine controversy continues. Reproductive Health Matters 1995;3(6):142-44. http://www.rhm-elsevier.com/article/0968-8080(95)90169-8/pdf.

[5] Shallat L. Business as usual for quinacrine sterilisation in Chile. Reproductive Health Matters 1995;3(6):144-46. http://www.rhm-elsevier.com/article/0968-8080(95)90170-1/pdf.

[6] Mudur G. Use of antibiotic in contraceptive trial sparks controversy. BMJ 2004;328(7433):188.

Summarised in: Law and Policy Round Up. Reproductive Health Matters 2004;12(24):2111. http://www.rhm-elsevier.com/article/S0968-8080(04)24153-2/pdf.

[7] Katz KR, Nanda K. A nonsurgical permanent contraception stakeholder advisory committee: FHI 360’s experience. Contraception 2015;92(2):139-42. http://www.sciencedirect.com/science/article/pii/S0010782415000384.

[8] Harrington EK et al. Conceptualizing risk and effectiveness: a qualitative study of women’s and providers’ perceptions of nonsurgical female permanent contraception. Contraception 2015;92(2):128-34. http://www.sciencedirect.com/science/article/pii/S0010782415000955.

[9] Health worker roles in providing safe abortion care and post-abortion contraception. Geneva: WHO Department of Reproductive Health and Research; July 2015. http://www.who.int/reproductivehealth/topics/unsafe_abortion/abortion-task-shifting/en/.

[10] Jensen JT. Nonsurgical permanent contraception for women: let’s complete the job. Contraception 2015;92(2):89-90. http://www.sciencedirect.com/science/article/pii/S0010782415002486.

[11] Harrington EK et al. Interest in nonsurgical female permanent contraception among men in Portland, Oregon and eastern Maharashtra, India. Contraception 2015;92(2):135-38. http://www.sciencedirect.com/science/article/pii/S0010782415001006.

[12] Berer M. Compelling arguments for developing new post-fertilisation methods of birth control. Berer Blog. 11 July 2015. https://bererblog.wordpress.com/2015/07/11/compelling-arguments-for-developing-new-post-fertilisation-methods-of-birth-control/.

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