Update on FHI's Current Research on Nonsurgical Sterilization, December 2007

See Also:

Female Sterilization

Female Sterilization and Menstrual Patterns

Male Sterilization

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

Preclinical Quinacrine Studies

As required by the U.S. Food and Drug Administration, FHI conducted two animal studies to evaluate the potential carcinogenicity of quinacrine:

• Neonatal mouse carcinogenicity study. Mice that received a systemic exposure to quinacrine — which is similar to humans given an oral dose of the drug — did not show an increased risk of cancer at the end of a one-year observation period.
• Rat carcinogenicity study. Quinacrine was administered directly into each rat's uterus, mimicking the proposed use of the drug as a contraceptive in women. The rat study showed a dose-related increase in cancers of the reproductive tract at the end of a two-year observation period.

Quinacrine Field Studies

For the past two decades FHI has been gathering long-term follow-up data on women who were exposed to quinacrine. These data are being used to examine the potential carcinogenicity of intrauterine quinacrine in humans. So far, no evidence has been found of an increased risk of cancer.

• Retrospective studies in Chile and Vietnam. Both of these epidemiological studies followed women who had received intrauterine quinacrine. The women in Chile had received quinacrine as part of FHI trials conducted in the late 1970s and 1980s. The women in Vietnam had received the drug under a program funded by the Ministry of Health. Neither long-term study showed a significant increase in the risk of cancer. While both studies have provided useful data on pregnancy rates and other outcomes, both are statistically limited because they included few participants relative to the number needed to determine cancer risk. Results from both studies have been published. However, additional data from Chile are being analyzed, and final results from 10 years of follow-up in Vietnam have been submitted for publication.
• Case-control study of gynecologic cancers in Vietnam. FHI is now completing a five-year 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 of the study should be available in 2008.

Additional Quinacrine Research

Although quinacrine field studies continue, FHI ceased its development of quinacrine for nonsurgical sterilization in November 2006 because of its potential carcinogenicity and unresolved concerns about its effectiveness as a contraceptive.

Erythromycin Development

A. Formulation

Erythromycin is a well-characterized drug, but it has not been studied for intrauterine administration for nonsurgical sterilization. FHI continues to develop a formulation of erythromycin for this indication:

• FHI is currently determining the parameters and physical properties of a formulation of erythromycin that can be used safely and effectively in a new erythromycin-based method of nonsurgical sterilization.
• An erythromycin formulation has been tested for safety in animals, and preparations are under way to test the safety of intrauterine administration of erythromycin in a phase I clinical trial in humans.

B. Preclinical Studies

FHI has developed a strategy for evaluating the safety of erythromycin and its possible formulations in animal models. This strategy includes evaluating possible clinical effects of the drug in the peritoneal cavity, vagina, and uterus. Additional animal studies may be required as other issues are discovered during development of this new method of nonsurgical sterilization.

C. Clinical Studies

FHI has received approval from the U.S. Food and Drug Administration to begin an early small-scale trial investigating a gel formulation for potential use by women. This first clinical study will involve a placebo gel formulation, which does not contain erythromycin or other active ingredients. A physician will insert the placebo gel into the uterus of study participants, and we will examine how the fluid moves into and out of the uterus and fallopian tubes. This should help to identify the features of the gel that are optimal for appropriate dosing, and to determine the best procedures for inserting the gel into the uterus. Future clinical trials of an erythromycin gel product are planned for 2008, pending the results of preclinical safety studies and the early trial investigating the gel formulation.