Advantage 24 is a new contraceptive gel that makes use of bioadhesive technology to offer 24 hours of protection relying on the spermicide nonoxynol-9 (N-9) in lower concentrations. If a proposed US Food and Drug Administration (FDA) rule is enforced N-9 may be examined closely. The manufacturer, Whitehall-Robins Healthcare in New Jersey, stopped production of the Today contraceptive sponge because of the costs of complying with FDA standards. The Advantage 24 gel costs twice as much as the sponge. It is made in Switzerland and distributed by an Illinois company. Any vaginal contraceptive containing N-9 would be approved by the FDA as long as it complied with guidelines laid down in an FDA monograph. However, the registration of the gel could not be confirmed. The product uses a bioadhesive technology concept that natural substances adhere to epithelial and mucosal tissues in the body. Polycarbofil is mixed with water, N-9, and mineral oil to create an emulsion that allows for a time-release mechanism, but at any given time only 2 mg of N-9 is available to kill sperm. The final formula for Advantage 24 is 52.5 mg per dose. Too much N-9 can be toxic, as demonstrated by the Today sponge, which contained 1000 mg of N-9. In Kenya prostitutes using it frequently experienced 3 times as many genital lesions as those using a placebo. A study of Advantage 24 by a Miami laboratory involved 250 women, 22-45 years old, who had had prior tubal ligations. When the gel was applied 15-30 minutes before intercourse the efficacy rate was 98%; it was 91% for those applying it 12 hours before; and it was 86% when the gel was applied 24 hours ahead of time. FDA compliance officers are intrigued about the claim that the gel lasts 24 hours. However, if the claim is held up by research data, women will have an easily available, portable, efficient, aesthetic, and highly effective contraceptive.

The effort to develop vaginal contraceptives began in the distant past and is still underway today. 1000 years ago, South American Indians inserted into the vagina bark strips impregnated with quinine. In medieval times women used vaginal inserts of cloth soaked in honey or vinegar. Quinine pessaries were introduced into Europe in the late 1800s, and in the early 1900s investigators began to study the effects of various chemicals on sperm motility. Following World War II, surfactant spermicides which disrupt the sperm membrane were developed and marketed. Many of these preparations contained nonoxynol-9. Currently, the D-isomer of propranolol is being examined as a spermicidal contraceptive, and several bacteriocides, e.g., benzalkonium and chlorhexidine, are being developed as spermicides which reduce the penetrability of cervical mucus. Other chemicals being investigated act by inhibiting the acrosome reaction. Advantages of vaginal contraceptives are that they are inexpensive, reversible, and relatively safe and easy to use. Generally they require no medical intervention or supervision. In addition, spermicides may kill or inhibit the growth of organisms responsible for sexually transmitted diseases. Disadvantages of spermicides are that they are generally less effective than many other methods, some interfere with sexual spontaneity, they may cause local irritations, and some women find them messy to use. Recently, concerns were expressed about the possible teratogenic effects of sperimicides. Most of these concerns proved to be unfounded. Given the many new avenues of research, the major disadvantage of sperimicides, i.e., their high failure rates, may be minimized in the near future.

Spermicides have long been used for vaginal contraception. Quinine was the prototype membrane-active drug used as a vaginal spermicide. Subsequently, propranolol, in both racemic and D-isomeric forms, has been shown to be a powerful inhibitor of sperm motility. The transmembrane migration ratio method was used to quantify the effects of various drugs with membrane stabilizing activity such as propranolol on sperm motility in vitro. Preliminary data from a clinical trial suggests that propranolol tablets used as a vaginal spermicide produce a pregnancy rate of between 3-4/100 women-years in a fertile population. Propranolol is extensively absorbed from the vagina since systolic blood pressure fell below baseline values and plasma concentrations were higher after vaginal administration than after oral administration. Pulse rates also declined. The clinical implications of these studies are discussed.

At the recent conference of the American College of Obstetricians and Gynecologists (ACOG), health care professionals concluded that, while there has been much speculative information in the past few years about the risks involved with vaginal contraceptives, women often prefer them over oral contraceptives (OCs) or an IUD. Dr. Gerald S. Bernstein, noted at the cervical cap symposium, sponsored by the Atlanta Feminist Women\'s Health Center, that the following are the most common vaginal contraceptive methods: solid barriers (cervical caps and diaphragms); vehicle barriers (contraceptive foams, creams, suppositories); or spermicides. Bernstein cited as major advantages of the methods their local action, their lack of systemic effects, and the few contraindications they may cause. The disadvantages included a requirement for user motivation, the association of some methods with coitus, inconvenience, messiness, and the necessity of manipulation. He also emphasized that the methods are less effective than the OCs or IUD in preventing pregnancy. Major safety issues or risks concerning vaginal and barrier methods are the toxicity of spermicides, effects of using spermicides after the user is pregnant, and trauma caused by some solid barriers. Whether or not spermicides used after a pregnancy occurs can cause congenital anomalies is still an unanswered question. It was Bernstein who discovered that the Vimule cervical cap could cause vaginal lesions of the portio vaginalis cervicis, ranging from erythematous impressions to abrasions and lacerations. He emphasized that trauma by a mechanical contraceptive device is probably not restricted to the Vimule cap. At this time Bernstein is completing a study to determine how long women should leave their cervical caps in place. Commenting that the cap is not yet approved for producation in the US, Dr. Daniel Mishell said at the ACOG conference that the vaginal contraceptive sponge is an attractive new means of vaginal contraception. The sponge, approved by the US Food and Drug Administration for 24 hour use, contains spermicide and is expected to have an efficacy rate similar to the diaphragm--in the 85% range. A new clinical study of women using the diaphragm with 2% nonoxynol-9 gel shows a failure rate much lower than average for other vaginal contraceptives. Dr. Bohdan Malyk reported that the combined method used in the 12-month independent study show a failure rate of 2.4%.

The recent award of $5.1 million by an Atlanta federal court judge to a woman who had used vaginal spermicide, Ortho-Gynol, and subsequently had a deformed baby has stirred up a major controversy and alarmed thousands of women. The ruling held that the child\'s abnormalities resulted from the mother\'s use of the spermicide which damaged but did not kill the sperm. It further held that Ortho Pharmaceutical Corporation, the manufacturer, was at fault for not warning women that this product could produce birth defects. Established medical data reveal that 2-5% of babies are born with some form of birth defect. In most instances their mothers were not exposed to any agent known to cause birth defects, and the reasons for those events are never determined. The question of whether spermicides cause fetal abnormalities has been extensively evaluated. 1 evaluation was completed by the US Food and Drug Administration\'s (FDA) Panel on Vaginal Contraceptive Durg Products for Over-the-Counter Human Use. That panel met almost monthly from 1973-78 to evaluate the safety and efficacy of vaginal preparations. The evaluation included reviewing available information about the ingredients used in spermicides. The ingredent in question, octoxynol, was included in the review as well as nonoxynol-9, another widely used spermicidal agent. The panel reported that there is no evidence thus far which suggests that these ingredients produced any such damage. In the early 1980s 2 reports demonstrated a slightly increased risk of birth defects in children of women using spermicides, but those studies were poorly designed and their conclusions were not substantiated by later, more accurate, and carefully conducted evaluations. In 1983 the FDA\'s Fertility and Maternal Health Drugs Advisory Committee again reviewed the evidence and unanimously concluded that women using spermicides were not at increased risk of having babies with birth defects. Responding to the recent legal ruling, experts from the Centers for Disease Control, the National Institutes of Health, the FDA, the March of Dimes, and other scientists who specialize in studying birth defects have corroborated that the overwhelming weight of the current medical evidence fails to indicate that spermicides cause fetal damage. Overreaction to the decision can be most unfortunate. Consumers should be aware that the recent ruling runs directly counter to current medical expert opinion.

Currently, the US Food and Drug Administration (FDA) is investigating a complaint that the Ramses Extra spermicidal condom may have caused severe pain in a user. The condom, which received marketing approval from FDA in 1982, contains the spermicidal lubricant nonoxynol-9, which reduces the number of active sperm and consequently decreases the risk of pregnancy. Lee Mathews of the FDA\'s office of compliance is investigating the complaint, filed in August 1983. The man experienced \"excruciating pain\" on urination after using the spermicidal condom, according to FDA documents. The woman indicated in the complaint that the pain possibly resulted from the condom\'s spermicide entering her husband\'s urethra. The pain subsided after several hours. She reported that her husband had never used the spermicidal condom before and had no known allergies or sensitivities. A spokeswoman for the manufacturer, Schmid Products, Company, reported after investigating the complaint that the company saw \"no reason to believe that there was a batch problem or a problem with that particular condom.\" Company records revealed no other complaints with that batch. No other samples were available for testing from the woman filing the complaint, but \"the fact that the wife did not have a problem also indicates there wasn\'t anything particularly wrong with that condom.\" Company officials did not interview the man who used the condom in question, but they did reply to him in writing and have heard nothing more from the couple. The Schmid spokeswoman indicated that there have been isolated instances of sensitivity to this product. A key factor behind FDA approval of the spermicidal condom was a study completed for Schmid by Dr. Edwin Dale. Dale\'s study involved 30 men, 19-46, who used both regular condoms and condoms treated with nonoxynol-9. He concluded that decreased sperm motility with the treated condoms was caused by cell fragmentation due to cell membrane disruption.

Concerns about the potential of nonoxynol-9 to irritate the vaginal mucosa have deterred the US Centers for Disease Control from endorsing use of this product for the prevention of sexually transmitted diseases (STDs), including HIV. To date, no manufacturers of over-the-counter spermicides have applied for product labeling changes. The US Food and Drug Administration recently held a joint committee meeting of four advisory panels aimed at encouraging spermicide manufacturers to submit clinical results pertaining to STD transmission. The committee concluded that, while manufacturers of over-the-counter spermicides may claim short-term protection against chlamydia and gonorrhea, the long-term safety of such products remains unclear. Needed are clinical trials that investigate the effects of spermicide-induced cervical and vaginal irritation on the risk of HIV transmission. The joint committee indicated that studies conducted in STD clinics and with commercial sex workers would be acceptable evidence. The National Institute of Allergy and Infectious Diseases soon will release the findings of a case-control study that used colposcopy to document the extent of epithelial erosion and other lesions associated with low doses of nonoxynol-9. Of continuing concern is the possibility that the labeling of spermicides as effective against STDs will reduce use of condoms, the most effective barrier to HIV transmission.

In a question-and-answer format, this article sets forth general information about nonoxynol-9, the findings of a two-year trial of nonoxynol-9 conducted among commercial sex workers in Cameroon, and the public health implications of recent clinical research. Although the US Food and Drug Administration granted approval in 1980 of nonoxynol-9 as a vaginal contraceptive method, concerns have been raised that frequent use of this spermicide or use in high concentrations tends to produce vaginal irritation and epithelial disruption, which may enhance transmission of sexually transmitted diseases (STDs) such as HIV. In the Cameroon study, 1292 HIV-negative female prostitutes received either nonoxynol-9 film or a placebo film; in addition, they were provided with condoms. The study found that the low-dose nonoxynol-9 film did not increase the risk of STDs; however, in settings where a high percentage of sex acts were protected by condoms, the spermicide did not provide any additional protection against STDs. The study was unable to assess whether use of spermicidal film alone conferred any protection against STD transmission. These findings suggest that consistent use of latex condoms, with or without spermicides, remains the best strategy for STD prevention.

The diaphragm is one of the least accepted methods of birth control by adolescents. It consists of a cup made of latex with a metallic ring at its base, its diameter ranges from 50 to 105 mm, and in its concave part a spermatocide can be placed to immobilize and destroy spermatozoa. It acts as a physical barrier to sperm at the cervical canal. By maintaining vaginal acidity and by making it difficult for cervical mucus to neutralize the vaginal ph, a hostile environment is created for spermatozoa. Its failure rate is 24-29 pregnancies per 100 women years. The right size has to be fitted to allow for the 3-5 cm increase in the depth of the vagina during sexual excitation in nullipara. It can be inserted 4-6 hours prior to intercourse in order not to interfere with sexual spontaneity, and removal should not occur until 8 hours later. Indication is for adolescents with infrequent sexual activity, those who stopped using the pill, or whose IUD had been removed. It is contraindicated for various medical conditions and infections. Toxic shock syndrome can occur, it it stays in too long. It offers some protection against sexually-transmitted diseases and cervical neoplasm due to the lack contact with the seminal fluid. Allergic reactions to spermatocides can occur in addition to various side effects due to ill-fitting diaphragms. The low acceptability by teenagers is attributable to its lower rate of effectiveness than the pill and little motivation for its use, although it should be recommended for those who are afraid of the side effects of the pill and IUD.

A recent court ruling has sparked concern about the future of spermicides as a contraceptive option. The 11th Circuit Court of Appeals in Atlanta recently upheld a multimillion-dollar award to a woman who claimed that Ortho Pharmaceutical\'s Ortho-Gynol spermicidal jelly caused her daughter\'s birth defects. Ortho was found negligent for failing to warn consumers through product labeling that birth defects could result if the jelly did not prevent conception. Ortho representatives maintain that no labeling is necessary since numerous studies have shown no association between birth anomalies and spermicide use. Although this is the 1st lawsuit over a spermicide-birth defects link, there is concern that an onslaught of litigation is upcoming. In the face of extended litigation, it is feared that the manufacturer will withdraw the product from the market. Family planning practitioners have expressed alarm about this possibility. Since teenagers and young adults, who tend not to visit family planning clinics, are the primary users of spermicides, a higher rate of unintended pregnancy is likely to result should the product be withdrawn.