1 Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.
2 Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.
3 Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA.
4 Department of Obstetrics and Gynecology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.
Received for publication August 2, 2001; accepted for publication January 14, 2002.
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ABSTRACT |
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contraceptive devices, female; follow-up studies; safety; sexually transmitted diseases
Abbreviations: Abbreviations: CFHC, California Family Health Council; PSA, prostate-specific antigen; STD, sexually transmitted disease.
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INTRODUCTION |
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Measuring the frequency of mechanical failure of the female condom is necessary to assess acceptability and efficacy of the device. For mechanical failure to have biologic significance, however, it must lead to exposure to semen or to male urogenital secretions. Semen exposure is not a common endpoint in breakage and slippage studies. It is not known whether semen exposure actually occurs with user-reported failure or can occur in its absence. In principle, semen exposure is better than self-report as a marker of condom failure and could replace more serious events (unwanted pregnancy, STDs) as the endpoint of efficacy studies. We used the presence of prostate-specific antigen (PSA) in vaginal fluid (5) as an objective marker of semen exposure and evaluated its association with self-reported problems.
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MATERIALS AND METHODS |
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Eligible women who gave informed consent participated in a group session promoting the female condom and providing use instructions. Each participant practiced insertion with an anatomic model and on herself, and a nurse practitioner verified correct placement of the device. Each woman was trained to take pre- and postcoital vaginal samples by using a swab; to complete a form describing her experience using the condom; to package the form, swabs, and used condom in separate, sealed bags; and to return these items to the project staff. The form included questions about the time and duration of intercourse, problems experienced, partner ejaculation, and time elapsed since previous intercourse. Potential problems listed on the form included those associated with the swabs, condom breakage and slippage, penile misrouting, semen leakage, noise, and discomfort.
The participant also completed a questionnaire measuring attitudes and beliefs about condoms and was given five female condoms to try with her partner. After using five condoms (training phase), each participant returned to review data forms with project staff and to review use problems with the nurse. She then entered the proficiency phase, used as many as 15 condoms following the procedures described above, and returned for a final visit to report on her experience.
The following mechanical problems experienced during intercourse were considered a priori as potential causes of semen exposure and condom failure: 1) the condom broke; 2) the condom came out of the vagina; 3) the penis entered to the side of the condom; 4) the outer ring was pushed inside the vagina; 5) semen leaked on the womans body; 6) the condom clung to the penis, moving with it; or 7) the woman had a problem with the inner ring during intercourse.
The following acceptability problems were considered as potential determinants of use discontinuation but not of failure: 1) vaginal bleeding (nonmenstrual) occurred, 2) the male or 3) the female partner felt pain or discomfort, and 4) the condom made noise.
All returned condoms were first examined to confirm use and to detect tears. Condoms without evident tears were rinsed, suspended from a 2 inch x 2 inch (5 cm x 5 cm) polyvinyl chloride (PVC) reducer coupling, and filled with 300 ml of water containing methylene blue. The outer surface of the condom was dried and, 5 minutes later, was gently patted with a white tissue (Kimwipes, Kimberly-Clarke Corporation, Atlanta, Georgia); blue marks on the tissue indicated breakage. The process was repeated 5 minutes later to increase test sensitivity.
Participants collected vaginal samples using an 8 inch (20 cm) gynecologic swab with a 3/8 inch (9.5 mm)-diameter rayon tip (Hardwood Products Company, Guilford, Maine) inserted in a 3 inch x 1/2 inch (7.6 cm x 1.3 cm) cardboard tube (Custom Paper Tubes, Cleveland, Ohio), which was perforated at one end to allow the swab handle to slide through. With each condom, the participant received two plastic zipper bags (one labeled Before to collect the precoital sample of vaginal fluid and one labeled After to collect the postcoital sample), each containing one swab and two packets of desiccant (Desiccite 25, Tigerpak Inc., Clifton, New Jersey). A nurse practitioner observed each participant take a vaginal sample, retract and anchor the swab in the tube, and seal the swab in the bag without touching the swab tip.
Dried swabs were stored at room temperature for extraction. The swab was placed in 3 ml of saline for 15 minutes, resulting in 2 ml of eluent. The latter was stored at 80°C until thawed for testing with the PSA IMx immunoassay (Abbott Laboratories, Abbott Park, Illinois). In these conditions, postcoital PSA levels of >1 ng/ml indicate recent (<24 hours) semen exposure (6). Thus, one condom use was classified as negative for semen exposure if the PSA level of the postcoital sample was 1 ng/ml. If the postcoital PSA level was >1 ng/ml, the precoital specimen was also tested for PSA.
To contain costs, PSA testing was limited to 1) all postcoital proficiency-phase samples, 2) all training-phase postcoital samples from participants who completed the study, 3) a sample of training-phase postcoital swabs from participants who did not complete the study, and 4) all precoital samples corresponding to PSA-positive postcoital samples.
The study protocol was reviewed and approved by the Institutional Review Boards of the University of Alabama at Birmingham and the Centers for Disease Control and Prevention (Atlanta, Georgia).
Similar sampling procedures, coupled with a less-sensitive PSA immunoassay, were used in a small-scale study of male condoms (7).
Data analysis
The first analysis included data from all condoms used in the study to evaluate the rates of self-reported problems (per 100 uses). Crude and stratum-specific rates (by training/proficiency phase or by the order of condom use) were computed as 100 x condom uses with reported problems/condom uses.
The second analysis evaluated the rate of semen exposure by using PSA data from pre- and postcoital swabs. Two criteria specified a lower and an upper boundary of the numerator of the semen exposure rate: 1) criterion Ithe lower boundary was defined by the number of condom uses in which a) postcoital PSA was >1 ng/ml and precoital PSA was 1 ng/ml and b) postcoital PSA was at least 22 ng/ml higher than precoital PSA; and 2) criterion IIthe upper boundary was defined by the number of condom uses in which a) postcoital PSA was >1 ng/ml and precoital PSA was
1 ng/ml or b) postcoital PSA was at least 22 ng/ml higher than precoital PSA.
These two criteria consist of the intersection and the union of conditions a) and b), respectively. Condition a) is sensitive to small variations in PSA levels and is likely to detect exposure to small quantities of semen, but it is also prone to false-positive results (e.g., from random variation in vaginal fluid sampling or PSA measurement). Conversely, condition b) imposes a minimum difference between pre- and postcoital PSA levels unlikely to be due to random variation (in a previous study, 22 ng/ml was the 95th percentile of the difference between any two samples taken by the same woman 24 hours after exposure to 1 ml of semen (8)), but it may miss true exposure to small quantities of semen. PSA levels in vaginal fluid increase sharply after semen exposure, returning to <1 ng/ml 2448 hours after exposure (8). To minimize exposure misclassification, estimation of semen exposure rates was restricted to condom uses that took place 24 hours after the previous act of intercourse.
The third analysis evaluated the association of semen exposure with self-reported problems. The odds ratio was the measure of association, and the significance of simple associations was evaluated by using a chi-square test. Adjusted odds ratios and their 95 percent confidence intervals were estimated by using logistic regression. The correlation of errors among condom uses pertaining to one person was modeled explicitly in generalized linear mixed models for binary outcomes (9). The order of condom use was forced in all models to adjust for experience with female condom use.
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RESULTS |
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Self-reported problems
A total of 2,232 female condoms were used by 175 women: 745 during the training phase and 1,487 during the proficiency phase (table 1). At least one mechanical problem was experienced in 17 percent of the uses. Only 15 condoms broke during use, or 0.7 per 100 uses. The most commonly reported mechanical problems (at rates of 37 per 100 uses) were that the condom rode on the penis, the condom came completely out of the vagina, and the outer ring was pushed inside the vagina. Additional mechanical problems (the penis entered outside the condom, semen leaked on the womans body, and inner ring problems occurred) were each reported in 12 percent of uses. Acceptability problems were reported during 12 percent of uses. Most prominently, the woman felt discomfort in 6 percent, and the man in 4 percent, of the uses (table 1).
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The difference between the training and the proficiency phase reflects a steady decline in the problems reported with number of condoms used, observed with both mechanical and acceptability problems (figure 1). Although more than 40 percent of the women reported problems with the first female condom used, 12 percent reported problems at the 20th use. The rates of mechanical and acceptability problems were 33 percent and 25 percent at the first use and 6 percent and 9 percent at the 20th use, respectively. Because the trend could be an artifact due to early discontinuation by women who frequently experienced problems (and would have maintained high problem rates after many uses had they stayed in the study), problem rates were computed separately for women who discontinued after using fewer than 20 condoms and for those who completed the protocol. The women who discontinued use early had higher problem rates than those who completed the protocol, but the decline remained evident among women who completed the protocol (data not shown).
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Specific mechanical problems associated with semen exposure were evaluated in a multiple regression model that also included number of condoms used and explicit terms for the correlation among condoms used by the same woman. Within-subject correlation was modest, and similar results were obtained if condom uses were treated as independent observations. The number of uses was inversely associated with semen exposure. Even after we controlled for correlation of repeated measurements and number of uses, condom breakage, misrouting of the penis, pushing of the outer ring into the vaginal cavity, and leakage of semen on the womans body were strong predictors of semen exposure (table 2). These associations were statistically significant in models in which either criterion I or criterion II was used to define the dependent variable, but they were stronger when exposure was classified by using criterion I. This finding is compatible with reduced exposure misclassification associated with criterion I but also with the tendency of the four mechanical problems to correlate with high semen exposure levels.
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DISCUSSION |
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Despite uncertainties about which semen exposure level indicates condom failure, it is clear that the female condom is successful as a barrier to semen: complete protection occurred in 7993 percent of the acts of intercourse in which the device was used. However, problems were common during female condom use (25 percent of more than 2,000 uses). Of the 175 women who returned one or more condoms, 83 percent reported problems (74 percent reported one or more mechanical problems, 61 percent reported one or more acceptability problems). Depending on the criterion used, 4371 percent of the 141 women contributing data to the third analysis were exposed to semen at least once during the study. Such high rates were observed despite state-of-the-art training of the participants. The number of reported problems was a strong predictor of discontinuation, suggesting that acceptability of the device for long-term use may be limited (Lawson et al., unpublished results). We recently reported that, in a large group of women at high risk of STD, most tried the female condom but few chose the device as their primary method of STD protection (10, 11).
Problem and semen exposure rates declined with use, suggesting an effect of experience on modifiable determinants of condom failure. We made similar observations for the male latex condom among women whose STD risk was high (12). On the other hand, relatively high problem and semen exposure rates persisted even after 20 uses.
User-reported problems were associated with semen exposure. In particular, breakage and other mechanical problems were associated with high rates of semen exposure and high postcoital PSA levels. A large number of user-reported problems did not result in semen exposure, however. Conversely, user-reported problems explain only a portion of the instances of exposure. To the extent that semen exposure is a biologic marker of condom failure, users do not detect a substantial proportion of condom failures while they report problems that do not entail exposure.
The biologic significance of low semen exposure is uncertain. It is plausible that small quantities of semen, leading to low PSA levels, bear a lower risk of pregnancy or STD than do large quantities of semen. However, low-level exposures may be associated with a significant risk of STD with low infectious doses.
Certain limitations must be acknowledged in interpreting the results of this investigation. First, the study was carried out with a select group of couples at low risk of STD. Thus, the findings may not be generalizable. However, low-risk couples are the target of phase II studies of new condoms, and it was important that the present investigation follow the guidelines for conducting such studies. A group of 895 women attending STD clinics in Alabama, who were trained by using similar methods and used 7,895 female condoms, reported 443 slippages (rate, 5.6 percent) and nine breakages (rate, 0.1 percent) (Macaluso et al., unpublished data). Thus, women whose risk of STD is higher, who may be more motivated to use the female condom correctly, may experience lower failure rates than those observed in this study.
Second, attrition was high; fewer than half of the participants completed the study. Women who contributed data to the analysis were not different from those who did not, with the exception that the women who did not complete follow-up more often disliked the appearance of the female condom and expressed aversion to inserting it (Lawson et al., unpublished data). In addition, because user problems are associated with increased risk of discontinuation and semen exposure, selective loss of couples who experienced problems and exposure led to underestimation of semen exposure. The cohort dynamics, though, are likely to reflect what would occur in the population, with many couples experimenting with the product and discontinuing use early, possibly because of high problem rates, and some couples continuing on and experiencing progressively lower rates of problems and exposure.
Finally, although the present study may represent an improvement over conventional designs based on only self-reported use and experiences, data collection was still dependent on subject participation. Accuracy of self-report may vary across subjects and should have led to our underestimating the frequency of problems and overestimating semen exposure in the absence of problems, which may in part explain semen exposure in the absence of reported problems. Furthermore, time since the previous act of intercourse may have been overestimated; this problem may explain why 25 percent of the precoital samples were positive for semen exposure even after we excluded condom uses reported to have occurred less than 24 hours after the previous act of intercourse. Exposure assessment was based on the comparison between samples taken before and after use, however, and condom uses in which precoital PSA values were elevated were excluded from the analyses.
Specimen collection also was dependent on the participants, and the swabs may have been contaminated with semen if the instructions for collecting the postcoital samples were not followed. The sampling device and the procedures were carefully designed to minimize the potential for contamination and were tested for acceptability. In contrast to condom use problems, problems with the sampling procedures were rare. Contamination of the postcoital swabs most likely occurred by touching exposed skin surfaces and would have often led to small increases in PSA levels in the sample. This mechanism may have led to overestimating the upper boundary of the semen exposure rate, but it is unlikely to have affected the lower boundary. The true rate of semen exposure during female condom use is likely to lie between 7 percent and 21 percent.
Despite these limitations, this study adds to our understanding of the efficacy of the female condom. First, it provides evidence that semen exposure is associated with user-reported problems, more often mechanical than acceptability related.
Second, the female condom provided complete protection in 7993 percent of uses. Although these rates suggest that protection is not perfect, comparable evidence about the male condom is lacking. In the CFHC study (7), the semen exposure rate during use of nonpunctured male condoms was about 6 percent, similar to the lower boundary of the semen exposure rate of the female condom. Thus, it would be premature to conclude that the female condom offers less protection than the male latex condom.
Finally, this study breaks new ground by using an endpoint that is not a serious adverse outcome. Assessing semen exposure may be a valid alternative to assessing pregnancy rates when evaluating the contraceptive efficacy of new condoms. The design does not require using a condom as the only method of contraception, and participants may minimize their risk by using another contraceptive method during the study. Women were able to help us collect data without being overburdened by protocol requirements, and the laboratory procedures provided accurate PSA levels (8). Overall, 175 women returned 4,464 vaginal samples during the study, demonstrating that the sampling procedures can be implemented on a large scale.
In conclusion, we developed objective methods for assessing female condom failure and integrated them with conventional self-report in a study of couples at low risk of pregnancy and STD. We found a clear association between self-reported mechanical problems and semen exposure, but the association was not perfect, suggesting that objective methods are necessary for a valid assessment of condom safety and efficacy. The female condom was an effective barrier to semen in the vast majority of uses. Further research is needed to determine which semen exposure levels, as measured by PSA, predict the risk for pregnancy and STD and to compare the female condom with the male condom. This evidence is necessary to make informed decisions regarding the role of the female condom in large-scale programs to promote barrier contraception to prevent unintended pregnancy and STD.
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ACKNOWLEDGMENTS |
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The authors are grateful to Dr. Joseph Petraglia for his assistance with editing the manuscript.
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NOTES |
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REFERENCES |
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