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Nonoxynol-9 vaginal pessary: a preliminary Indian experience.

BACKGROUND: Barrier methods of contraception do not have systemic effects and allow the user complete control over their use. For women, the ease of use of a contraceptive is often more important than its efficacy. Hence, barrier methods could be offered as a useful alternative method of contraception. Nonoxynol-9 (a spermicide) is a locally acting, non-hormonal method free from systemic side-efforts. It is a woman-controlled, reversible method which is to be used before intercourse. There are little data available on its efficacy, side-effects and acceptability among Indian women. METHODS: The vaginal pessary nonoxynol-9 was offered as a contraceptive option to 3200 women attending the Family Planning clinics at 31 Human Reproduction Research Centres (HRRCs) of the Indian Council of Medical Research. The other contraceptives offered included an intrauterine device, oral pills, condoms, Norplant, tubal sterilization and vasectomy using the cafeteria approach. Those who accepted nonoxynol-9 were followed up to assess the rates of continuation, failure and side-effects. RESULTS: The nonoxynol-9 pessary was accepted by 541 women who were followed up for 3470 woman-months of use. The reasons given for acceptance were that it was user-controlled and/or they did not wish to use other methods because of the side-effects or contraindications of these methods. The overall continuation rates were 41.2% and 33% at 9 and 12 months of use, respectively. Most women (31.3%) discontinued its use due to personal reasons such as husband dissatisfaction, desire for further pregnancy, irregular use of pessary and difficulty in insertion. Twenty-nine women became pregnant during the study period (15 due to method failure and 14 due to user failure) giving a use-effectiveness of 8.8% at 12 months. The method failure rate was 4.3% at 12 months of use. The failure rates were lower compared with the reported failure rates of barrier contraceptives (1%-30% at 1 year of use) and the side-effects were minimal. CONCLUSION: Nonoxynol-9 had low acceptability (16.9%) and overall continuation rates--41.2% and 33% at 9 and 12 months of use. It could be offered to women looking for a short term, user-controlled contraceptive.

Adolescent↗

Contact photosensitivity to nonoxynol used in antiseptic preparations.

Nonoxynols are nonionic surface-active agents used as surfactant in numerous cosmetic products and antiseptic preparations. Recently nonoxynol contact allergy has been described. We report two patients who presented a contact photosensitivity to nonoxynol 10 contained in Hexomédine transcutanée. Among 32 control subjects, we found 13 positive photopatch tests to Hexomédine transcutanée and 4 positive photopatch tests to nonoxynol 10. Surprisingly, the authors observed that only undiluted nonoxynol was phototoxic.

Administration, Cutaneous↗

Comparative vaginal spermicidal studies in the stumptailed macaque with alkyloxynol-741, nonoxynol-9 and chlorhexidine.

Alkyloxynol-741 ("agent 741") is used in the People's Republic of China as a substitute for nonoxynol-9 in vaginal contraceptive formulations. However, no studies are available that compare the effectiveness of these agents as vaginal spermicides. For this reason, dissolvable polyvinylalcohol (PVA) films were prepared containing various concentrations of alkyloxynol-741 and nonoxynol-9. Films were also prepared containing chlorhexidine, a potentially new vaginal contraceptive agent. Postcoital vaginal spermicidal studies were performed with the films in the stumptailed macaque (Macaca arctoides). The order of spermicidal potency was: alkyloxynol-741 greater than nonoxynol-9 greater than chlorhexidine. These observations suggest that alkyloxynol-741 can be used instead of nonoxynol-9 in those countries where alkyloxynol-741 is more readily available and can be obtained at a lower cost.

Animals↗

Compatibility between the spermicide nonoxynol 9 and mid-cycle human cervical mucus.

The rate of diffusion of [125I]-nonoxynol 9 into mid-cycle human cervical mucus was measured and found to be negligible compared with D-glucose (used as an uncharged small molecule for comparison with nonoxynol 9). These data were confirmed by observation of the lack of inhibition of the movement of spermatozoa in mucus that had been in surface contact, for 3 hours, with a concentration 30 times greater than the ED100 of nonoxynol 9. These results show that the entry of nonoxynol 9 into mucus could be minimal under conditions that would exist in vivo and highlights a limitation of this compound as a vaginal contraceptive.

Cervix Mucus↗

The spermicidal compound nonoxynol-9 increases adhesion of Candida species to human epithelial cells in vitro.

All 25 strains of Candida spp. tested were able to grow in medium supplemented with 25% nonoxynol-9 in vitro. Adhesion of Candida spp. to HeLa cells was found to increase in the presence of 5% nonoxynol-9 (2.2- to 6.6-fold; P less than 0.001) and, to a lesser extent, in 12.5% nonoxynol-9. Adhesion of Candida strains cultured in medium supplemented with nonoxynol-9 varied, with five of six strains of Candida albicans and the single strain of Candida tropicalis demonstrating increases of 1.4 to 4.0 times control levels (P less than 0.05). The increased adhesion did not correlate with altered yeast cell surface hydrophobicity or germ tube formation.

Adhesiveness↗

Effect of nonoxynol-9 gel on urogenital gonorrhea and chlamydial infection: a randomized controlled trial.

CONTEXT: Nonoxynol-9 has been suggested as a vaginal microbicide to protect against common sexually transmitted infections. OBJECTIVE: To compare nonoxynol-9 gel and condom use (gel group) vs condom use alone (condom group) for the prevention of male-to-female transmission of urogenital gonococcal and chlamydial infection. DESIGN AND SETTING: Randomized controlled trial conducted at 10 community clinics and 10 pharmacies in Yaoundé, Cameroon, between October 1998 and September 2000, with 6 months of follow-up. PARTICIPANTS: High-risk population of 1251 women (excluding sex workers) being treated for or who had symptoms of sexually transmitted infections. Three were excluded from the gel group (0.5%) and 7 from the condom group (1%) because of no follow-up data. INTERVENTIONS: Nonoxynol-9 gel (100 mg) and condoms or condoms only. MAIN OUTCOME MEASURE: A positive test result for gonococcal or chlamydial infection by the ligase chain reaction assay; secondary outcome measure was a positive test result for human immunodeficiency virus (HIV). RESULTS: The rate ratio (RR) for new urogenital infections was 1.2 for the gel group vs condom group (95% confidence interval [CI], 0.9-1.6; P =.21). The gel group had 116 diagnosed gonococcal infections, chlamydial infections, or both for a rate of 43.6 per 100 person-years, and the condom group had 100 infections for a rate of 36.6 per 100 person-years. The RR for gonococcal infection in the gel group vs the condom group was 1.5 (95% CI, 1.0-2.3) and for chlamydial infection was 1.0 (95% CI, 0.7-1.4). There were 5 new cases of HIV infections in the gel group and 4 in the condom group. Three women in each group became pregnant during the study. CONCLUSION: Nonoxynol-9 gel did not protect against urogenital gonococcal or chlamydial infection.

Adult↗

Hydrogen peroxide production by Lactobacillus species: correlation with susceptibility to the spermicidal compound nonoxynol-9.

Facultative anaerobic lactobacilli were recovered from the vaginas of 96.8% of 63 nonpregnant, healthy, premenopausal women. The predominant species were Lactobacillus jensenii, Lactobacillus acidophilus, and Lactobacillus casei. Of the women, 74.6% had hydrogen peroxide-producing lactobacilli, 22.2% had non-hydrogen peroxide-producing lactobacilli, and 3.2% had no lactobacilli. None of the 68 isolates had catalase activity. Some 68.2% of the isolates were inhibited by concentrations of less than or equal to 1% (wt/vol) of nonoxynol-9 (bactericidal for 73.3% of isolates, bacteriostatic for 26.7%). The remaining 31.8% could grow in all concentrations to 25% (wt/vol) of nonoxynol-9. All of the lactobacilli that were sensitive to nonoxynol-9 produced hydrogen peroxide whereas only 3 of 21 resistant strains were hydrogen peroxide producers. A significant correlation (P less than .001, chi 2 test) was found between hydrogen peroxide production and sensitivity to nonoxynol-9. It is suggested that the vaginal flora of spermicide users could be depleted of hydrogen peroxide-producing lactobacilli, possibly increasing susceptibility to urogenital infection.

Adult↗

Incidence of acute urinary tract infection in young women and use of male condoms with and without nonoxynol-9 spermicides.

BACKGROUND: Acute urinary tract infection is one of the most common infections seen in primary care. METHODS: We conducted a nested case-control study among a cohort of 519 women, ages 15-29 years, enrolled in a contraceptive acceptability study to examine whether recent use of male condoms increases urinary tract infection risk. RESULTS: One hundred sixty-five incident urinary tract infections were identified during 12-month follow-up periods in a cohort study that was conducted between 1996 and 1999. After exclusions for urinary tract infection recurrences, pregnancy, antibiotic use, diabetes, diaphragm/cervical cap use, or urinary tract abnormalities, there were 100 cases and 200 controls. Compared with women not using barrier methods (and after adjustment for age, urinary tract infection history, hormonal method use, and frequency of sex) the odds ratio (OR) for any reported use of condoms coated with spermicide (Nonoxynol-9) in the previous 30 days was 2.8 (95% [confidence interval] CI = 1.2-6.5). The OR was 11.5 (95% CI = 2.5-53) for exclusive Nonoxynol-9-coated condom use. The OR for exclusive use of non-Nonoxynol-9-coated condoms was 7.4 (95% CI = 1.6-35). CONCLUSIONS: In this study, use of male condoms was associated with increased urinary tract infection risk; the largest risk was associated with exclusive condom use and use of Nonoxynol-9-coated condoms.

Acute Disease↗

Rectal applications of nonoxynol-9 cause tissue disruption in a monkey model.

BACKGROUND: Efforts to develop topical microbicide products have all but ignored evaluation for rectal use. GOAL: The goal of this study was to assess the effects of multiple rectal applications of Conceptrol (containing 4% nonoxynol-9) on flora and mucosal tissues in the pig-tailed macaque model. STUDY DESIGN: Monkeys (8 per group) received daily rectal applications of Conceptrol, placebo gel, or no product, for 3 days. At each visit, a preapplication rectal lavage specimen and swab specimen for microbiology and pH determination were collected. Conceptrol or placebo gel (2.5 ml) was then administered intrarectally. Fifteen minutes after application, samples were again collected. RESULTS: Gross observation of rectal lavage indicated sheets of epithelium 15 minutes after application of the nonoxynol-9 product. Histopathology of these samples revealed epithelial sheets with stroma attached. The presence of H(2)O(2)-producing lactobacilli remained relatively constant, whereas that of H(2)O(2)-producing viridans streptococci diminished in all nonoxynol-9-exposed animals in which these organisms were detected at baseline. CONCLUSIONS: Repeated applications of nonoxynol-9 disrupts the rectal mucosa of the pig-tailed macaque. The disruption of these tissues could have serious implications for an increase in likelihood of acquisition of sexually transmitted infection/HIV in humans.

Administration, Rectal↗

Contraceptive effectiveness and safety of five nonoxynol-9 spermicides: a randomized trial.

OBJECTIVES: To estimate and compare the effectiveness and safety of 5 spermicides over 6 and 7 months of use, respectively. The spermicides included 3 gels containing 52.5 mg, 100 mg, and 150 mg of nonoxynol-9 per dose and a film and a suppository, each containing 100 mg of nonoxynol-9 per dose. METHODS: Women wishing to use only spermicide for contraception for 7 months were randomly assigned to use 1 of the 5 spermicides with emergency contraception backup. Participants were followed up for up to 30 weeks after admission. RESULTS: Of 1,536 women enrolled, 868 (57%) either relied on the spermicide for 6 months or became pregnant. The probability of pregnancy during 6 months of typical use of the spermicide was 22% (95% confidence limits 16%, 28%) in the 52.5-mg gel group, 16% (10%, 21%) in the 100-mg gel group, 14% (9%, 19%) in the 150-mg gel group, 12% (7%, 17%) in the film group, and 10% (6%, 15%) in the suppository group. The pregnancy risk in the 52.5-mg gel group was significantly different (P <.05) from that in either of the other gel groups. The pregnancy risks in the three 100-mg product groups were not significantly different (P =.35). No significant differences among groups were found in the 7-month probability of specified urogenital conditions. CONCLUSION: The gel with the lowest amount of nonoxynol-9 was less effective than the 2 higher-dose gels. Among 3 products containing 100 mg of nonoxynol-9, formulation did not significantly affect pregnancy risk. All products were safe. LEVEL OF EVIDENCE: I

Adolescent↗

In vitro activity of the spermicide nonoxynol-9 against Chlamydia trachomatis.

The in vitro activity of nonoxynol-9 against four serotypes (C, D, H, and K) of Chlamydia trachomatis was investigated. A constant inoculum of each serotype was exposed to serial twofold dilutions (1:100 to 1:800) of Koromex, Conceptrol, or reference preparations (not containing nonoxynol-9) for 4 and 24 h at 37 degrees C. The mixtures of nonoxynal-9 or nonnonoxynol preparations and control inocula were dispensed into triplicate wells containing McCoy cell monolayers. After incubation at 37 degrees C, the monolayers were fixed and stained with iodine and examined for evidence of infection with C. trachomatis. All nonoxynol-9-containing preparations showed marked antichlamydial activity as judged by percent reduction of glycogen-containing intracytoplasmic inclusions. The reference preparations, which did not contain nonoxynol-9, were markedly less active when tested in this in vitro system.

Chlamydia trachomatis↗

The protective effect of condoms and nonoxynol-9 against HIV infection.

OBJECTIVES: Whether or not spermicides can reduce the risk of human immunodeficiency virus (HIV) transmission remains an important question for the control of heterosexual HIV transmission. The authors provide estimates from a reanalysis of one of the few observational studies on the efficacy of condoms and spermicides, used separately and together, per vaginal contact. METHODS: In this reanalysis, three different models were used to assess the efficacy of spermicides and condoms: linear (Pearl index), exponential (maximum likelihood), and monotonic (marginal likelihood). RESULTS: Reported use of barrier methods among 27,432 contacts was as follows: condoms plus nonoxynol-9, 39%; condoms alone, 25%; nonoxynol-9 alone, 24%; and unprotected, 11%. Under all three models, the results indicate a strong protective effect for spermicidal suppositories. The Pearl index indicated that spermicide alone is apparently efficacious, but the efficacy per contact cannot be quantified with this approach. Maximum likelihood estimates for the efficacy of nonoxynol-9 alone and condoms (with or without nonoxynol-9) were 100% (95% confidence interval [CI95] = 43%, 100%) and 92% (95% CI95 = 79%, 100%), respectively. CONCLUSIONS: The data from this observational study suggest that spermicides may be efficacious in reducing the risk of HIV transmission.

Administration, Intravaginal↗

A simple, sensitive assay for the spermicide nonoxynol-9 in biological fluids by high-performance liquid chromatography.

A new high-performance liquid chromatographic technique has been developed to quantitate nonoxynol-9 in serum, urine, and vaginal fluid. The method is rapid, involves minimal sample preparation, and can be used to analyze a large number of biological fluid samples. The assay elutes a single nonoxynol-9 peak with no interfering components. This was accomplished using a 10-microns pelicular packed amine column, a normal-phase solvent system, and fluorescence detection. Nonoxynol-9 levels as low as 0.23 micrograms/mL in urine can be detected.

Body Fluids↗

Comparison of the potency of d-propranolol, chlorhexidine and nonoxynol-9 in the Sander-Cramer test.

The potency of two new candidate spermicides, d-propranolol and chlorhexidine, was compared with an established agent nonoxynol-9 by the Sander-Cramer test. The lowest concentrations of nonoxynol-9, d-propranolol and chlorhexidine which consistently inhibited progressive forward sperm motility within twenty seconds were found to be 0.12, 0.44, and 4.81 mg/ml, respectively. These relative potencies and other properties of d-propranolol and chlorhexidine indicate that they should be further investigated as alternatives to nonoxynol-9 in spermicidal preparations.

Chlorhexidine↗

Determination of the spermicide nonoxynol-9 in vaginal lavage by high-performance liquid chromatography.

A sensitive normal-phase high-performance liquid chromatographic method using a bonded-phase aminosilica column has been developed for the measurement of the spermicide nonoxynol-9 in vaginal lavage fluid. The mean multiple correlation coefficient (r2) for nonoxynol-9 was 0.999 over the calibration range 3.125-50 micrograms/ml for the standards. Quality control samples measured at two different concentration levels gave intra-day precision values (coefficient of variation, C.V.) in the range of 0.61 to 1.63% and the intra-day accuracy values (mean relative error, M.R.E.) in the range of 0.13-0.62%. Inter-day precision and accuracy values from five different calibration standard concentration values ranged from 2.25 to 5.09% C.V. and 4.02 to 7.56% M.R.E. Nonoxynol-9 samples examined for peak area stability at room temperature over a 24-h time period had a M.R.E. of 14.9%. Quality control samples stored at -70 degrees C, and tested after one month by comparison to baseline samples, had a M.R.E. of -10% and 7.53% for the low and high quality control samples, respectively. The method is sensitive and simple, with short runtimes, to enable the processing of numerous samples from a clinical trial.

Calibration↗

The impact of the use of COL-1492, a nonoxynol-9 vaginal gel, on the presence of cervical human papillomavirus in female sex workers.

This study investigated the effectiveness of a nonoxynol-9 (52.5mg, 3.5%), vaginal gel (Advantage S), in the prevention of human papillomavirus (HPV) infection in female sex workers. We showed by HPV DNA determination in cervico-vaginal rinses a significant increase in multiple (>1) HPV infection in HIV-1 seropositive women compared with HIV-1 seronegative women (OR 4.0, 95% CI 1.3-11.9). We also demonstrated a significant increase in multiple HPV infections in HIV-1 seronegative women using nonoxynol-9 compared with HIV-1 seronegative women using placebo (OR 3.5 95% CI 1.0-11.8). We conclude that the use of nonoxynol-9 did not prevent genital HPV infection and could increase the virus' ability to infect or persist.

Administration, Intravaginal↗

Contact sensitivity to nonoxynols as a cause of intolerance to antiseptic preparations.

Twelve cases of allergic contact dermatitis caused by antiseptic preparations are presented. The reactions resulted not from the active principles but rather from nonoxynols used in the offending substances as nonionic surface-active agents. Nonoxynols are ethoxylated alkyl phenols or nonylphenylethers that conform in general to the formula C9H19C6H4(OCH2CH2)nOH. They have emulsifying, wetting, foaming, and solubilizing properties and are used in a large number of industrial, household, agricultural, cosmetic, and pharmaceutical products. They also are used as spermicides. There are very few reports in the literature of skin problems caused by nonoxynols.

Adult↗

Solubilization and in vitro spermicidal assessment of nonoxynol-9 and selected fractions using rabbit spermatozoa.

Selected oligomers representing the high, medium, and low molecular weight fractions of the spermicidal agent Nonoxynol-9 (N-9) were separated by HPLC. Nonoxynol-9 and the isolated fractions were formulated with polyvinylpyrrolidone (PVP) in order to increase their water solubility, particularly that of the insoluble low molecular weight fraction. The in vitro spermicidal activity of three molecular weight fractions were compared to that of N-9, using rabbit spermatozoa, at equimolar concentrations. Nonoxynol-9/PVP was far more effective in immobilizing the sperm than either N-9 alone or the separate fractions. The relative spermicidal activity of the oligomers was of the order middle molecular weight greater than high molecular weight greater than low molecular weight.

Animals↗