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How should family planning clinicians proceed when it comes to advising their patients on currently available over-the-counter (OTC) spermicides for protection against such sexually transmitted diseases (STDs) as chlamydia and gonorrhea?
While nonoxynol-9 (N-9), the active ingredient in many spermicides, has been found effective in preventing these STDs,1 concerns about its potential for vaginal irritation cloud the prevention issue. Such irritation to the vaginal mucosa might actually increase the risk of HIV transmission, studies show.2
These concerns have kept the Atlanta-based Centers for Disease Control and Prevention and other groups from recommending the use of products containing N-9 to prevent STDs and HIV, notes David W. Feigal Jr., MD, MPH, acting office director for the Food and Drug Administration’s (FDA’s) Office of Drug Evaluation IV, in Rockville, MD.
The FDA recently held a joint committee meeting of four advisory panels in its effort to encourage spermicide manufacturers to submit clinical results pertaining to STD transmission. While the committee members voted 11-1 that spermicides could be said to help reduce the risk of chlamydia and gonorrhea, they were less clear on the safety of the long-term use of these products.
"The question that is unanswered at this point in time is under what conditions can significant vaginal irritation occur?" asks Penny Hitchcock, DVM, chief of the STD branch of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, MD. "That has got to be answered experimentally. We have got to do the clinical trials to show that we do not increase the risk of HIV infection by causing vaginal and cervical irritation.
"And until those data are available, responsible clinicians are where they were before the FDA hearings, and that is in a quandary as to how to answer the question for women."
It’s important to understand that no spermicide manufacturer has yet applied to the FDA to change current labeling to reflect claims for reduced risk of chlamydia or gonorrhea, Feigal notes.
"We have had sponsors ask whether the types of studies that have been done in STD clinics and with commercial sex workers would be adequate to support such a use, even though those populations are different than the general public that would be the target population," he says. "We asked the joint committees if that type of evidence could be used for a more general population, and that is what they voted positively on."
Committee members did express reservations, though, on the impact of any spermicide STD protection claims on the use of condoms, currently the most effective method for blocking HIV transmission. There have been no product substitution studies to see how consumer labeling of N-9 products would affect condom use, Feigal notes.
"Before manufacturers can make [any] such claim we must modify the monograph [that grandfathered the use of OTC spermicides as safe and effective], or approve a supplemental application to a New Drug Application," says Feigal. "What the meeting did was to let companies know that they could base their effectiveness data on the studies in STD clinics and sex workers and that they would have to also propose labeling [and include label comprehension studies if it is consumer labeling] and studies on product substitution. The meeting was intended to make the regulatory path clear to encourage applications."
Results are due out this spring from a National Institute of Allergy and Infectious Diseases-sponsored study on N-9 for HIV prevention. It uses lower doses of N-9, with colposcopy performed to document the extent of epithelial erosion and other lesions in the N-9 users vs. the control group.
"If the product is found to substantially increase risk, we will certainly need to modify product labeling and think about the setting for use, even for contraception," says Feigal. "If the product decreases risk, then we will need to rapidly look for ways to develop consumer and professional labeling to spread the news on how to use the product to decrease STD/HIV risk.
"If the data remains equivocal, we would at least consider professional labeling about gonorrhea/chlamydia, so long as it can be balanced against the lack of evidence for protection against HIV and the information that condoms remain more effective."
Study results can’t come soon enough, says Hitchcock.
"The concern is, what if we recommend women use a product, that instead of protecting them, could decrease their natural resistance?" she ponders. "And that’s a very, very difficult position for us to be in right now, but I would argue that’s exactly where we are. In spite of the fact that very thoughtful and credible agencies are recommending the use of spermicides, especially if there’s no other option for the women, it is of great concern to me, and to many other people, that we don’t know the answers to these questions. And yet we’re telling women to use something that we don’t know is safe."
1. Louv WC, Austin H, Alexander WJ, et al. A clinical trial of nonoxynol-9 for preventing gonococcal and chlamydial infections. J Infect Dis 1988; 158(3):518-523.
2. Bird KD. The use of spermicide containing nonoxynol-9 in the prevention of HIV infection. AIDS 1991; 5:791-796.