A two-year FHI study concludes that vaginal spermicial film is safe to use but does not
confer any additional protection to women from HIV, gonorrhea or chlamydia infections
beyond the protection provided by condoms. A question and answer column and summary of
selective previous N-9 research are included.
FHI collaborated with the Cameroon Ministry of Public Health to conduct the study in
the African country. The research, designed to assess a spermicidal film containing
nonoxynol-9 (N-9), did not address whether N-9 film used alone offers STD protection.
Ronald E. Roddy, MPH, an FHI epidemiologist, and Leopold Zekeng, PhD, a Cameroon ministry
HIV specialist, were the principal investigators.
Latex condoms offer the best STD protection for people at risk, but many women are
unable to persuade their partners to use them. FHI believes protective measures that are
used and controlled by women are urgently needed.
"Unfortunately, the news is not good for women, since we had hoped N-9 might
increase their available options for HIV protection," says Willard Cates Jr., MD,
MPH, FHI's senior vice president for biomedical affairs. "We must accelerate research
dedicated to finding new methods for women at risk of HIV and other STDs." HIV is the
virus that causes AIDS.
N-9 is available worldwide in many formulations, including foams, gels, suppositories
and creams. Women who use diaphragms, for example, typically apply N-9 cream or jelly to
the diaphragm, and some latex condom lubricants include N-9. None of these other products
were examined in the study. Also, the study only examined women and did not consider
whether N-9 film protects men.
The study was supported by a $1.6 million grant from the National Institute of Allergy
and Infectious Diseases (NIAID). "Correct and consistent condom use is highly
effective, but women must depend on the willingness of their partners to use male
condoms," says Dr. Rodney Hoff of NIAID's AIDS prevention program. "We and other
public health officials are committed to developing an STD/HIV prevention method that can
be controlled by women. This study is one part of that ongoing effort."
FHI believes the study is the most thorough examination to date involving an N-9
spermicide and the role spermicides play in protecting women against STDs. The finding
raises doubts about the additional benefit from using N-9 film as a prophylactic against
STDs with condoms. It does not alter FHI's advice to people who are at risk from infection
with HIV or other STDs -- they should use latex condoms correctly and consistently. An
alternative option for many women is to use the female condom, which may provide STD
protection if used consistently and correctly. Abstinence or a mutually monogamous
relationship between uninfected partners are the most reliable ways of preventing STD
infection.
Earlier, smaller N-9 studies had suggested that N-9 may reduce the risk of bacterial
STD infections, but were inconclusive about whether N-9 prevents HIV infections. The new
study involved 1,292 sex workers in Cameroon who volunteered at clinics to take part in
the study between March 1995 and December 1996. To be eligible, the women could not be
infected with HIV at the time they entered the study. Of the eligible volunteers, 478 who
were provided a contraceptive film containing N-9 and 463 who were provided a placebo film
that did not contain a spermicide, completed the study.
Each woman who asked about participating in the study received counseling to discourage
her from continuing as a sex worker (prostitution), an activity that places one at great
risk of acquiring HIV or other STD infections.
Volunteer participants who remained at risk were given condoms and urged to use them
with every act of intercourse. They received a new supply of condoms frequently, and were
examined monthly and treated for infections.
"The Cameroonian study staff strongly urged volunteers to practice safer
sex," says Dr. Zekeng of Cameroon. Volunteers from the cities of Yaoundé and Douala
received thorough counseling and were asked to return monthly for medical attention, which
FHI believes significantly reduced the risks they otherwise would have faced. "Study
participants were helped to adopt protective behaviors, which reduced their rate of
infection by more than 50 percent," Dr. Zekeng says.
For the women completing the study, 147,996 acts of sexual intercourse in the group
using N-9 film and condoms were compared with 146,942 acts in the group provided with the
placebo film and condoms. The rate of HIV transmission was nearly the same for both
groups. For every 100 women using N-9 film and condoms for one year (100 woman-years), 6.7
became infected with HIV, compared with 6.6 HIV infections using the placebo film and
condoms.
The comparable rates for gonorrhea infections were 33.3 infections for N-9 and condoms
to 31.1 for placebo film and condoms per 100 woman-years. Infection rates for chlamydia
were 20.6 for N-9 and condoms and 22.2 for placebo film and condoms per 100 woman-years.
A theoretical concern has been whether frequent use of N-9 may increase the risk of STD
infections, since frequent use of the chemical may cause sores that could enhance
transmission. Women in the study reported using the film more frequently than do most
women who use N-9. This study did not show any increased risk of HIV or other STD
infections from using N-9 film, although genital lesions (sores) did occur slightly more
often among women who used N-9. There were 42.2 lesions per 100 woman-years among women
using N-9 and condoms, compared with 33.5 lesions among women using the placebo film and
condoms.
The study has certain limitations. Because of the paramount concern for the safety of
participants, they were counseled to use condoms every time they had sex, the only proven
method of protection. Since few women reported using film without condoms, the study
cannot conclusively address whether N-9 film alone offers any protection from HIV or other
STDs.
Worldwide, about two thirds of all HIV-infected people live in the sub-Saharan region
of Africa. One benefit of the study is that it demonstrates that HIV prevention research
among people at high risk of infection can be done according to the highest ethical
standards.
The film used in the study is made by Apothecus Pharmaceutical Corp., Oyster Bay, NY
and is available under the brand name of VCF Vaginal Contraceptive Film.
N-9 Contraceptive Film and
the Risk of STDs
The following questions and answers are grouped to address typical questions involving
general information about N-9; the recent study by FHI and the Cameroon Ministry of Public
Health; and the public health policy implications.
General information
What is nonoxynol-9 (N-9)?
Nonoxynol-9 (N-9) is a detergent-like chemical that has been used for more than 40
years in vaginal products to prevent pregnancy. N-9 prevents pregnancy by disrupting the
outer surface of sperm, resulting in its death. Because N-9 kills sperm, it is known as a
spermicide.
What products contain N-9?
In the United States, N-9 is found in a variety of vaginal spermicides including gels,
creams, foams, suppositories, and film. Some of these products are meant to be used by
themselves and others are meant to be used with a diaphragm or cervical cap. In other
countries, N-9 is also found in spermicidal foaming tablets. N-9 is also added to certain
lubricated condoms.
Do all spermicides contain N-9?
No, but most spermicidal products sold in the United States use this chemical. Other
common spermicides used around the world are menfegol, a chemical used in spermicidal
foaming tablets (widely used in Asia) and benzalkonium chloride (BZK), the ingredient
widely used in products manufactured in France.
Is N-9 safe to use as a contraceptive?
Yes. In 1980, based on three decades of clinical experience, the U.S. Food and Drug
Administration (FDA) determined that N-9 is safe and effective as a vaginal contraceptive.
The safety of N-9 for vaginal use is based both on animal safety testing and on the
absence of reported adverse reactions over decades of experience in humans using N-9
containing spermicidal products for contraception. For some women, N-9 causes vaginal
itching and burning, which ceases when they stop using the product. N-9 may also cause
similar symptoms in male sexual partners.
Are all N-9 products the same?
No. These products are available in different formulations, as gels, creams, foams,
suppositories, and film. Also, spermicidal products on the market use different
concentrations of N-9 (ranging from 52.5 mg to 150 mg for a typical dose). The film used
in the FHI Cameroon N-9 film trial contains 70 mg of N-9.
Cameroon study results
Why are scientists examining N-9, a contraceptive, as a way
to prevent STDs?
In the laboratory, N-9 kills HIV and other STD pathogens by disrupting the outer coat
of the viruses and bacteria that cause the diseases, thereby killing these organisms.
Also, small studies among people using N-9 have suggested that the contraceptive may
protect against STDs. However, the ability of N-9 to prevent HIV or other infections in
actual use had not been rigorously studied.
Another concern about the use of N-9 to prevent STDs is whether frequent use of N-9, or
use in high concentrations, may actually increase the risk of STD transmission. Frequent
use or high concentrations can irritate the cells that line the vagina and cervix
(epithelial disruption) causing inflammation, which could theoretically lead to easier
access by HIV or other microorganisms.
What did the FHI Cameroon study conclude about N-9 and STD
infections?
This two-year study concluded that using N-9 film in settings where a high percentage
of sex acts were protected by condoms does not offer women any protection against HIV,
gonorrhea or chlamydia, in addition to that protection conferred by condoms alone. The
study also concluded that using N-9 did not increase the risk of being infected by these
STDs. The study could not determine if spermicidal film used alone offers STD protection.
Have these results been published in a scientific journal?
Not yet. A careful epidemiological analysis of the study data has only recently been
completed, and this analysis has not yet been published. As with all FHI research, our
findings will be submitted to appropriate peer-review scientific journals to be considered
for publication. Because this study gives new, vitally important insights into N-9 use and
STD prevention, FHI believes its findings should be made available immediately, so that
women who might depend upon N-9 for STD protection are aware of this research.
How was the study conducted to reach these conclusions?
The study involved 1,292 sex workers (prostitutes) in Cameroon who volunteered at
clinics to take part in the study between March 1995 and December 1996. All women who
considered volunteering were strongly encouraged to discontinue their risky behavior
(multiple partners), since this places them at great risk for STD infection. Those who
continued their risky behavior and who were enrolled in the study were given condoms
frequently, and urged to use them with every act of intercourse.
To be eligible, women could not be infected with HIV when enrolled. Volunteer women in
the study were assigned to use either the N-9 film or a placebo (inactive) film, prior to
having sexual intercourse. The difference between the two films was explained to them, but
participants did not know whether they were using N-9 film or the placebo. The volunteers
were periodically assessed for infection with HIV or other STDs, and were asked about any
symptoms that might be ascribed to film use.
Of the eligible volunteers, 478 completed the study using a contraceptive film
containing N-9 and 463 completed the study using a placebo film that did not contain the
spermicide. Based on a careful statistical analysis that considered numerous factors,
including the number of sexual acts and whether condoms were also used, a rate of STD
transmission was determined for each group and these rates were compared.
Were study participants paid?
No. Participants received free medical examinations, care and counseling, free condoms
and N-9 or placebo film, and were reimbursed modest transportation costs to clinics.
Who conducted the study?
The study was conducted by research scientists at the Cameroon Ministry of Public
Health and Family Health International, a nonprofit research organization that specializes
in reproductive health. It was sponsored by the U.S. National Institute of Allergy and
Infectious Diseases (NIAID).
Who approved this study?
The scientific importance of the study was reviewed and approved by a group of
non-government scientists who recommended that NIAID fund the study. Prior to starting the
study, the study protocol was reviewed and approved by ethical review boards in Cameroon
and at Family Health International. At FHI, a Protection of Human Subjects Committee
monitors all research involving people. The eight voting members of the FHI panel are not
FHI employees and come from a variety of professional backgrounds, including law, consumer
interests and the clergy.
In addition, NIAID reviewed the study to assure that it met U.S. government regulations
for biomedical research. To assure that the study was being conducted in an ethical manner
and that the volunteers were not being exposed to undue risks, intermediate results during
the course of the research were reviewed by NIAID's independent Data and Safety Monitoring
Board, which is composed of scientists from universities and other institutions that were
not involved in the study. The U.S. Food and Drug Administration (FDA) was not asked to
approve this study because the manufacturer was not seeking specific FDA approval for use
of this film in preventing HIV.
Who paid for this study, and how much did it cost?
The study was financed with a $1.6 million grant from the U.S. National Institute of
Allergy and Infectious Disease (NIAID). The U.S. Agency for International Development and
the Mellon Foundation provided financial support for development of the study.
Why was the study done in Africa and not in the United
States?
In general, research involving infectious disease is conducted among people who are
most exposed to the disease. Two of every three HIV-infected people worldwide live in
sub-Saharan Africa. Among sex workers in sub-Saharan Africa, the risk of HIV infection is
especially high. Because of the study's paramount concern for encouraging condom use and
reducing the risk of infection, a desirable consequence of doing the study in Cameroon was
to promote prevention strategies among women who are at great risk of HIV infection.
Conducting the study in Cameroon not only improves scientific quality, but reduces the
risk of HIV and other STD infections for participants.
Why was the N-9 contraceptive film studied, and not other
N-9 products?
The N-9 film was chosen because it offers a low dose of N-9 (70 mg of N-9), thereby
minimizing potential irritation to the vaginal tissue. Also, it is already available over
the counter in the U.S., has a good safety profile, and it is relatively easy to use. The
relatively low cost of the product suggested that it had a better chance of being
available for use in developing countries such as Cameroon if it were found to be
effective in preventing STDs. The film used in the study is manufactured by Apothecus
Pharmaceutical Corp., a U.S. company based in Oyster Bay, NY. In the United States, the
film is available over-the-counter in more than 25,000 drug stores and pharmacies and is
provided by more than 6,000 family planning clinics, according to the company. The film
sells under the brand name of VCF Vaginal Contraceptive Film.
Public health implications
What are the implications of this study for people at risk
of HIV and other STDs?
Unfortunately, this study is not encouraging for people at risk of STDs, especially for
women who cannot persuade their partners to use latex condoms. For these women, the female
condom is one option that may provide STD protection if used consistently and correctly.
FHI believes research to develop new options for protecting people from HIV and other STDs
is urgently needed.
Anyone at risk of STDs should be aware that correct and consistent use of latex condoms
is considered the best protective measure. Abstinence and a mutually monogamous
relationship between uninfected partners are considered the most reliable ways of avoiding
infection.
What does the U.S. Centers for Disease Control and
Prevention (CDC) currently recommend regarding the prevention of HIV infection?
Currently, the CDC recommends that latex condoms with or without spermicides should be
used to prevent HIV transmission among sexually active individuals at risk. FHI strongly
supports this recommendation. No data currently exist to indicate that condoms lubricated
with spermicides are more effective than other lubricated condoms in protecting against
transmission of HIV and other STDs.
Are there other studies of N-9 products in progress?
Yes. A study is under way in Kenya to evaluate the efficacy of a low-dose N-9 gel in
preventing HIV transmission. Another study of the same N-9 gel, sponsored by the Joint
United Nations Programme on HIV/AIDS (UNAIDS) program, is also under way in several
countries in Africa and Asia. A preliminary study to determine the safety of N-9 gel when
used rectally is under way in the United States.
Selected Research Involving
N-9 and STDs
| The following is a chronological bibliography of key studies on
nonoxynol-9 (N-9) and prevention of sexually transmitted diseases (STDs). In all
prospective studies where volunteer participants were at risk of HIV, participants were
encouraged to use latex condoms consistently and correctly, the best protection for people
at risk of STDs, and they were counseled about STD risks and ways to reduce their risks.
Participants were frequently examined for STDs and were treated. |
| Zekeng L, Feldblum PJ, Oliver RM, Kaptue L. Barrier contraceptive
use and HIV infection among high-risk women in Cameroon. AIDS 1993; 7(5):725-31. An
observational study conducted among 273 female sex workers in Cameroon concluded that
women who used N-9 or latex condoms consistently had a significant reduction in HIV
infection rates -- the first time a study had reported epidemiological evidence that N-9
may protect against HIV. Half of the women reported using condoms for 63 percent or more
of sexual acts, while half reported using spermicide for at least 67 percent of coital
acts. Volunteer participants were advised to use non-spermicidal male lubricated condoms
and a vaginal suppository containing 100 mg of N-9 each time they had sexual intercourse.
The study, which lasted 12 months, was conducted by the National AIDS Control Service in
Yaoundé and Family Health International.
A later analysis of this data concluded that use of vaginal N-9 suppositories did not
increase the incidence of genital ulcers. Previous research had suggested that frequent
N-9 use can lead to genital irritation and ulceration. Ulcers could be a possible risk
factor for HIV. (Weir SS, Roddy RE, Zekeng L, Feldblum PJ. Nonoxynol-9 use, genital
ulcers, and HIV infection in a cohort of sex workers. Genitourin Med 1995; 71:78-81).
Another examination of the data set concluded that male latex condoms offered significant
protection against gonorrhea. (Weir SS, Feldblum PJ, Zekeng L, Roddy RE. The use of
nonoxynol-9 for protection against cervical gonorrhea. Am J Public Health 1994;
84(6):910-14.)
Feldblum PJ, Weir SS. The protective effect of nonoxynol-9 against HIV infection
(letter). Am J Public Health 1994; 84(6):1032-34.
Reanalysis of data collected among sex workers in Cameroon reaffirmed findings from the
original observational study that N-9 use may offer some protection against HIV. The
reanalysis, conducted by FHI, found that the more consistent the use of N-9, the lower HIV
rates were. Researchers also found that the rate of HIV infection decreased as condom use
increased.
Kreiss J, Ngugi E, Holmes K, Ndinya-Achola J, Waiyaki P, Roberts PL, Ruminjo I,
Sajabi R, Kimata J, Fleming TR, Anzala A, Holton D, Plummer F. Efficacy of nonoxynol 9
contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi
prostitutes. JAMA 1992; 268(4):477-82.
A randomized controlled trial of N-9 contraceptive sponge use among sex workers in
Nairobi, Kenya concluded that the N-9 sponge did not appear to protect against HIV. Women
who used the N-9 sponge had a three-fold increase in incidence of genital ulcers, which
has been considered a risk factor for acquisition of HIV, and a higher risk of vulvitis.
However, N-9 users had a 60 percent reduced risk of gonorrhea, said the study's
researchers from the University of Washington at Seattle, University of Nairobi,
University of Manitoba, and Kenya Medical Research Institute. Seventy-four women were
randomly assigned to use the N-9 polyurethane sponge. Women were asked to insert the
sponge each day before having sex, to use one sponge for two to three sex partners, and to
remove the last sponge six hours after last sexual intercourse. Sixty-four women were told
to insert a placebo gylcerine vaginal suppository (later a water-based vaginal cream) once
daily before intercourse with their first sex partner of the day.
Niruthisard S, Roddy RE, Chutivongse S. Use of nonoxynol-9 and reduction in rate of
gonococcal and chlamydial cervical infections. Lancet 1992; 339:1371-75.
The effects of N-9 in preventing chlamydia and gonorrhea were examined in this 1990
randomized controlled trial, which was conducted in Bangkok, Thailand by FHI and
Chulalongkorn University. Researchers compared infection rates among 186 women who used
N-9 film and condoms with 157 women who used condoms and a placebo film. Volunteer
participants were women who worked at massage parlors and had an average of two to three
sexual partners per day. Researchers found that, overall, use of N-9 decreased the rate of
gonococcal and chlamydial cervical infection by 25 percent. For women who used N-9 for
more than 75 percent of sexual acts, the rate of infection declined by 40 percent. For
women who used N-9 for fewer sexual acts, N-9 appeared to offer little protection from
cervical infection. Condoms offered greater protection against gonorrhea and chlamydia
than did N-9 alone. There was no difference in the development of genital ulcers or
vaginal yeast infections in either group. N-9 users complained more frequently about
genital irritation, including burning, itching, and soreness, although symptoms were not
considered severe.
Rosenberg MJ, Rojanapithayakorn W, Feldblum PJ, Higgins JE. Effect of the
contraceptive sponge on chlamydial infection, gonorrhea and candidiasis: a comparative
trial. JAMA 1987; 257(17):2308-12.
Women who used the N-9 sponge had lower rates of chlamydia (29 percent of sponge users
and 51 percent of nonusers after seven weeks) and the incidence of gonorrhea was also
lower among sponge users (8 percent in the N-9 group compared with 40 percent in the
control group) in a randomized controlled trial in Bangkok, Thailand among 492 sex workers
from massage parlors. Sponge users had a higher incidence of candidiasis than nonusers (12
percent versus 4 percent, respectively). Half of the volunteer participants were assigned
to use the N-9 sponge while 246 were assigned to the control group. Women were asked to
continue their regular family planning method, in most cases oral or injectable
contraceptives, and encouraged to use condoms. The study was conducted by FHI and the Thai
Ministry of Public Health.
Louv WC, Austin H, Alexander WJ, Stagno S, Cheeks J. A clinical trial of nonoxynol-9
for preventing gonococcal and chlamydial infections. J Infect Dis 1988; 158:518-23.
In this randomized controlled study of 818 women, researchers from the University of
Alabama at Birmingham and Jefferson County Department of Health, Birmingham, evaluated the
ability of N-9 to prevent gonorrhea and chlamydia. Study participants were clients at
clinics that treat sexually transmitted diseases. One group of participants was asked to
use a commercially available spermicide gel containing N-9, while the control group was
asked to use a placebo. After six months, researchers concluded that women who used N-9
were less likely to develop gonorrhea or chlamydia than women in the placebo group. The
more consistent was the N-9 use, the lower were the rates of cervical infection. A second
study, published in the American Journal of Obstetrics and Gynecology in August 1990,
evaluated spermicide use among the same group of women and found that women who used N-9
had a lower incidence of trichomoniasis and bacterial vaginosis than did women in a
placebo group. There was no difference in the incidence of candidiasis.
Kelaghan J, Rubin GL, Ory HW, Layde PM. Barrier-method contraceptives and pelvic
inflammatory disease. JAMA 1982; 248(2):184-87.
Researchers at the U.S. Centers for Disease Control and Prevention found that women who
used barrier contraceptives (condoms, N-9 spermicides, diaphragms with N-9 spermicide)
were less likely to develop pelvic inflammatory disease (PID) than women who used other
contraceptives or no contraceptives. PID is a serious illness for women and can lead to
infertility or death. Researchers analyzed the data from the Women's Health Study, a large
multicenter case-controlled study conducted in the United States from 1976 to 1978.
Researchers compared the contraceptive methods used by 645 women hospitalized for PID with
the methods used by 2,509 women with no history of PID.
Further reading
Centers for Disease Control and Prevention. Update: barrier protection against HIV
infection and other sexually transmitted diseases. MMWR 1993; 42(3): 589-91, 597.
This paper summaries several scientific studies that have concluded that male latex
condoms can effectively protect against HIV transmission. For couples who are
serodiscordant (one is HIV-positive and the other is HIV-negative), using latex condoms
consistently and correctly reduced the risk of HIV transmission. Latex condoms reduced the
risk of gonorrhea, herpes simplex, genital ulcers and pelvic inflammatory disease. Latex
condoms also provided a physical barrier against transmission of hepatitis B, chlamydia
and gonorrhea.
Feldblum PJ, Morrison CS, Roddy RE, Cates W Jr. The effectiveness of barrier methods
of contraception in preventing the spread of HIV. AIDS 1995;(Suppl A): S85-S93.
This article gives an overview of research on chemical and physical barrier methods and
their ability to prevent sexually transmitted diseases, including in vitro and in vivo
data on male condom use and spermicide use and information on irritation, consistency of
use, and future research needs.
Elias CJ, Coggins C, Atisook R, Bassett MT, Ettiegne-Traore V, Ghys PD,
Jenkins-Woelk L, Thongkrajai E, VanDevanter NL. Women's Preferences Regarding the
Formulation of the Over-the-Counter Vaginal Spermicides. Presentation at the XI
International Conference on AIDS. July 7-12, 1996. Vancouver, Canada.
A survey of 138 women in Cote d'Ivoire, Thailand, United States and Zimbabwe on their
preferences for spermicide formulations (gel, suppository, film) found that women's
preferences were influenced by such factors as lubricant or drying effect, effects on
sexual pleasure and frequency of use. |
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