Evaluating the potential of quinacrine for sterilization

See Also:

Female Sterilization

Female Sterilization and Menstrual Patterns

February 2003 Research on Nonsurgical Sterilization

Male Sterilization

Network: Male and Female Sterilization; Vol 18, No 1

For more than two decades, scientists at Family Health International (FHI) have been searching for a safe and effective way to provide nonsurgical sterilization for women. In the late 1970s and through much of the 1980s, FHI conducted a number of small clinical trials in Chile and the United States to explore the potential of intrauterine quinacrine. Although the drug had a long history as a pill for the treatment and prevention of malaria, the effects of intrauterine administrations of quinacrine had not been closely examined.

FHI's early trials on intrauterine quinacrine had mixed results. Scientists had concerns about its efficacy and the need for three separate insertions of the drug into the uterus. Also, a follow-up of the participants in Chile identified a cluster of cancer cases among women who had received quinacrine. Because of these concerns, FHI decided to halt research on quinacrine in 1989, but continued to follow the participants' health status.

FHI then began a long-term follow-up study of the women in Chile, which included an analysis of cancer rates and pregnancy rates. A careful examination of the cancer cases in Chile led FHI and external experts to conclude that the cluster was a random event, but some concern remained about a single case of an unusual type of uterine cancer. FHI's analysis of pregnancy rates also suggested that two intrauterine insertions of quinacrine were just as effective as three insertions. These findings led to a renewed interest in quinacrine by FHI researchers and extended the follow-up of the women in Chile.

FHI was subsequently invited to conduct an epidemiologic study of women in Vietnam who had received quinacrine under a program funded by the Ministry of Health. The epidemiological studies of women in Chile and in Vietnam who received intrauterine quinacrine did not show a significant increase in the risk of cancer, but both investigations were statistically limited because each had relatively few participants. Even so, both studies provided useful information on long-term pregnancy rates among women who used quinacrine. After two quinacrine insertions and five years of follow-up, the cumulative pregnancy rate in Vietnam was 9.8 percent compared to a rate of 6.4 percent in Chile.

Following FDA recommendations, FHI began laboratory research between 1994 and 2006 to develop a quinacrine-based product that could be used for nonsurgical female sterilization. The investigations included studies of quinacrine's genotoxicity and carcinogenicity. The genotoxicity tests in prokaryotic cells and mammalian cells confirmed other investigations, which showed that quinacrine is a mutagen in vitro, but does not cause chromosomal breaks in vivo.

FHI then conducted two studies of carcinogenicity in rodents, one in mice, and one in rats. Mice that received a systemic exposure to quinacrine — which is similar to humans given an oral dose of quinacrine — did not show an increased risk of cancer at the end of the one-year observation period. However, a two-year study of rats that received doses of quinacrine directly into the uterus, showed a dose-related increase in cancers of the reproductive tract.

The potential carcinogenicity of quinacrine, combined with unresolved concerns about the drug's effectiveness as a contraceptive, led FHI to cease its development of quinacrine for nonsurgical sterilization in November 2006. FHI is now completing a case-control study of women with gynecologic cancers in northern Vietnam to determine whether there is any association with exposure to intrauterine quinacrine. The results should be available in 2008.

FHI continues to believe that finding an easily administered method of nonsurgical sterilization — which is safe, effective, and inexpensive — would be a valuable contribution to the field of family planning. FHI will continue its efforts to develop such a product.

Reference List

Feldblum PJ, Hays M, Zipper J, et al. Pregnancy rates among Chilean women who had non-surgical sterilization with quinacrine pellets between 1977 and 1989. Contraception 2000;61(6):379–84.

Hieu DT, Luong TT, Anh PT, et al. The acceptability, efficacy and safety of quinacrine non-surgical sterilization (QS), tubectomy and vasectomy in 5 provinces in the Red River Delta, Vietnam: a follow-up of 15,190 cases. Int J Gynaecol Obstet 2003;83 Suppl 2:S77–85.

Hieu DT, Tan TT, Tan DN, et al. Maternal and Child Health/Family Planning Department, Ministry of Health, Hanoi, Vietnam. 31,781 cases of non-surgical female sterilisation with quinacrine pellets in Vietnam [see comments]. Lancet 1993;342(8865):213–7.

Ogburn T, Espey E. Transcervical sterilization: past, present, and future. Obstet Gynecol Clin North Am 2007;34(1):57–72, viii.

Sokal D, Hieu DT, Weiner DH, et al. Long-term follow-up after quinacrine sterilization in Vietnam. Part II: interim safety analysis. Fertil Steril 2000;74(6):1092–101.

Sokal D, Hieu DT, Weiner DH, et al. Long-term follow-up after quinacrine sterilization in Vietnam. Part I: interim efficacy analysis. Fertil Steril 2000;74(6):1084–91.

Sokal DC, Dabancens A, Guzman-Serani R, et al. Cancer risk among women sterilized with transcervical quinacrine in Chile: an update through 1996. Fertil Steril 2000 Jul;74(1):169–71.

Sokal DC, Haneke K, Robinson E, et al. FHI's Decision to Halt Development of Quinacrine: Why and How. Poster P48. Association of Reproductive Health Professionals Annual Meeting Minneapolis, MN, September 28, 2007.

Zipper J, Cole LP, Goldsmith A, et al. Quinacrine hydrochloride pellets: preliminary data on a nonsurgical method of female sterilization. International Journal of Gynaecology & Obstetrics 1980;18(4):275-9.