Comparison of self-reported female condom failure and biomarker-confirmed semen exposure.

OBJECTIVE: To investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a contraceptive efficacy substudy. STUDY DESIGN: We structured our comparative analysis to assess whether functionality studies might credibly supplant contraceptive efficacy studies when evaluating new female condom products. Couples not at risk of pregnancy in the functionality (breakage/slippage/invagination/penile misdirection) study and women in the contraceptive efficacy study completed condom self-reports and collected precoital and postcoital vaginal samples for up to four uses of the WC. Both studies used nearly identical self-report questions and the same self-sampling procedures and laboratory for prostatic specific antigen (PSA), a well-studied semen biomarker. We compared condom failure and semen exposure proportions using generalized estimating equations methods accounting for within-couple correlation. RESULTS: Ninety-five (95) efficacy substudy participants used 334 WC and 408 functionality participants used 1572 WC. Based on self-report, 19.2% WC (64 condoms) clinically failed in the efficacy substudy compared to 12.3% WC (194 condoms) in the functionality study (p=.03). Of the 207 WC efficacy uses with evaluable postcoital PSA levels, 14.5% (30 uses) resulted in semen exposure compared to 14.2% (184 uses) of the 1293 evaluable WC functionality study uses. CONCLUSIONS: When evaluating the ability of an experimental condom to prevent semen exposure, the rate of clinical condom failure reported by participants risking pregnancy in an efficacy substudy was significantly higher than the rate reported by participants not risking pregnancy in a functionality study. The rate of semen exposure, assessed by an objective biomarker was nearly identical for the two studies. IMPLICATIONS: Our results suggest that an objective marker of semen exposure in functionality studies could provide a reasonable alternative to contraceptive efficacy studies in evaluating risk of unintended pregnancy and inferring protection from sexually transmitted infection than condom failure rates based on self-report.

Acceptability of the Woman's Condom in a phase III multicenter open-label study.

OBJECTIVE: This study aimed to evaluate the acceptability of the Woman's Condom (WC) over 6 months (183 days) and ≥6 menstrual cycles in a US-based multicenter open-label phase III contraceptive efficacy trial. STUDY DESIGN: We assessed acceptability via written questionnaire at visit 2 (after the third cycle) and visit 3 (after the sixth cycle or >183 days, or upon early discontinuation). Key domains included ease of use, comfort/lubrication, sexual satisfaction, male partner satisfaction and confidence in pregnancy and sexually transmitted infection (STI) prevention. We analyzed quantitative data using descriptive statistics. We conducted a content analysis to identify major themes from four open-ended questions. RESULTS: Most women [327/405 (81%)] had limited or no previous experience with female (internal) condoms. Of 405 evaluable women, 346 women completed questionnaires at visit 2 and 303 women at visit 3; 282 women attended both visits. Of women attending both visits, 165/282 (59%) reported at visit 2 that WC insertion was easy/very easy; this increased to 195/282 (69%) at visit 3 (p=.03). Many women [166/281 (59%)] preferred the WC [105/281 (37%)] or were neutral [61/281 (22%)], while 115/281 (41%) preferred male condoms. Women attending visit 3 felt confident that the WC could prevent pregnancy [246/303 (81%)] and STIs [217/303 (72%)]. Many women expressed empowerment with having control over their contraception; some disliked the design, esthetics and insertion process. Most women (254/299 (85%)] would recommend the WC to a friend. CONCLUSION: The WC's acceptability and ease of use is promising for wider dissemination as a female-controlled method that can protect against both pregnancy and STIs. IMPLICATIONS: The WC's overall acceptability and ease of use is promising for a new female-controlled barrier contraceptive option that can protect against both pregnancy and sexually transmitted infections.

Contraceptive efficacy, acceptability, and safety of C31G and nonoxynol-9 spermicidal gels: a randomized controlled trial.

OBJECTIVE: To estimate whether a gel containing the spermicide C31G was noninferior to a commercially available product containing nonoxynol-9. METHODS: Participants were healthy, sexually active women aged 18-40 years. Measured outcomes included pregnancy rates, continuation rates, adverse events, and acceptability. The primary study outcome was contraceptive efficacy. Sample size was calculated at a 2.5% significance level using a one-sided test based on assumed 6-month pregnancy probability of 15% in the nonoxynol-9 group. Sample size was sufficient to reject, with 80% power, the null hypothesis that pregnancy probability in the C31G arm would be more than 5% higher. RESULTS: Nine hundred thirty-two women were randomized in the C31G group and 633 in the nonoxynol-9 group. For randomized patients with at least one episode of coitus (modified intent-to-treat group), 6-month pregnancy probabilities were 12.0% (95% confidence interval [CI] 9.3-14.7%) and 12.0% (95% CI 8.7-15.3%) for C31G and nonoxynol-9,respectively. Twelve-month pregnancy probabilities were 13.8% (95% CI 7.6-20%) for C31G and 19.8% (95% CI 10.9-28.7%) for nonoxynol-9. Two serious adverse events were deemed possibly related to study product and neither occurred in the C31G group. Three fourths of users in either group reported that they liked their assigned study product. Approximately 40% of patients discontinued prematurely for reasons other than pregnancy with 11% lost to follow-up. CONCLUSION: C31G demonstrated noninferior contraceptive efficacy compared with nonoxynol-9. C31G may provide another marketable option for women seeking spermicidal contraception. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00274261.

Noncomparative contraceptive efficacy of cellulose sulfate gel.

OBJECTIVE: To estimate the 6-month cumulative probability of pregnancy, short-term adverse effects, and acceptability of cellulose sulfate vaginal contraceptive gel. METHODS: Two hundred fertile heterosexual couples were enrolled in this single-center, phase II, 6-month noncomparative study conducted at the California Family Health Council in Los Angeles, California. Couples did not desire pregnancy, were at low risk for sexually transmitted diseases, and agreed to use 3.5 mL of cellulose sulfate gel intravaginally before each coital act as their primary means of contraception. Scheduled follow-up visits took place after one menstrual cycle and at study completion, which occurred after 6 months and six menstrual cycles had elapsed. In addition, participants were instructed to call the site at the onset of each menses to review their diary cards. RESULTS: The cumulative probabilities of pregnancy during 6 months and six cycles of typical use were 13.4% (95% confidence interval [CI] 7.5-19.4%) and 13.9% (95% CI 7.7-20.2%), respectively, and during 6 cycles of correct and consistent ("perfect") use: 3.9% (95% CI 0.0-9.2%). Slightly over one fourth of the women and one man reported experiencing gel-related adverse events, two thirds of which were mild and only possibly related to the gel. Three quarters of women and men reported that they would buy cellulose sulfate gel for contraception. CONCLUSION: Cellulose sulfate vaginal gel yields pregnancy rates comparable to nonoxynol-9 and few adverse events among couples at low risk for sexually transmitted diseases.

Patterns of emergency contraception use by age and ethnicity from a randomized trial comparing advance provision and information only.

PURPOSE: This study measures the impact of the advance provision of emergency contraception (EC) among family planning clients at 31 clinics in California. METHODS: We randomized over 9000 clients to receive a packet containing either two 0.75-mg levonorgestrel pills (Plan B) or an identical packet containing EC information only. We conducted follow-up interviews on a subset of 1130 clients selected to optimize the age and ethnicity distribution. The interviews collected information on EC use, contraception, risk-taking behaviors and EC attitudes. RESULTS: Clients who received EC in advance were significantly more likely to have used EC (19%) than women who received information only (12%) (p=.0009). There were no significant differences between the contraceptive and risk-taking behavior of the two treatment groups. Study respondents of all ages and ethnicities expressed positive attitudes about EC. Nevertheless, even with EC on-hand, many respondents who reported unprotected intercourse decided not to take EC. CONCLUSION: More research should be done on the reasons women decide not to use EC even when readily available.

Effectiveness of the male latex condom: combined results for three popular condom brands used as controls in randomized clinical trials.

BACKGROUND: Although public health programs invest heavily in the male latex condom, its efficacy in preventing pregnancy and sexually transmitted disease has been based primarily on in vitro and retrospective studies. METHODS: We combine the results from two randomized, controlled contraceptive efficacy trials that used commercial latex condoms brands (Ramses Sensitol, LifeStyles, Trojan-Enz) in the control arms. Combining data from the two studies, we obtained longitudinal data covering 3526 menstrual cycles contributed by approximately 800 couples who used latex condoms exclusively for up to six menstrual cycles. Both trials also collected 3715 detailed breakage and slippage reports from the first five study condom uses. The second trial also tested 243 postcoital vaginal samples collected after the first study condom use for the presence of prostate-specific antigen (PSA) and spermatazoa. RESULTS: The combined clinical breakage rate for the first five condom uses was 0.4% for the three latex brands and the combined clinical slippage rate was 1.1%. The combined six-cycle typical-use pregnancy rate for the latex condoms was 7.0% (95% confidence interval 5.0-9.0). The combined six-cycle consistent-use pregnancy rate was 1.0% (95% confidence interval 0.0-2.1). PSA was detected in only 1.2% of postcoital vaginal samples collected after the first use of an intact study condom. There were no differences in performance or efficacy among the three latex brands tested. CONCLUSIONS: The male latex condoms rarely broke or slipped off during intercourse and provided high contraceptive efficacy, especially when used consistently. Risk of semen leakage from intact condoms was very low.

Male tolerance study of 1% C31G.

BACKGROUND: C31G is being studied as a vaginal contraceptive and microbicide. This study was conducted to ensure that male partners of the women in future trials of C31G will not be subjected to an undue risk of penile irritation. METHODS: This was a randomized, double-blinded, single-center Phase I study in circumcised and uncircumcised men to assess penile irritation, safety and acceptability of seven consecutive daily doses of 1.0% C31G compared with a marketed spermicide, Extra Strength Gynol II(R) (3% nonoxynol-9) (ES Gynol II). Each participant was instructed to apply the study product to his penis at bedtime, to wash it off 6-10 h later, and to record any symptoms on a diary card. At the follow-up visit, a genital examination was performed and participants were again asked about adverse events and to complete an acceptability questionnaire. RESULTS: Of the 36 men enrolled, 12.5% of C31G users and 16.7% of Extra Strength Gynol II users reported product-related adverse events (AEs). All product-related AEs were considered mild by the investigator, except for one in the ES Gynol II group. Both products were acceptable. CONCLUSION: The manner in which the products were used in this study is not the route by which men will be exposed to such products in actual use, and results should be considered in this light. Based on the observations in this study, C31G appears to be at least as safe and acceptable for male penile exposure as the marketed product ES Gynol II.

Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men.

OBJECTIVES: To assess safety and acceptability of penile application of BufferGel (ReProtect, Baltimore, MD) and PRO 2000 Gel (Indevus Pharmaceuticals, Lexington, MA)compared with placebo among low-risk sexually abstinent men and HIV-positive sexually abstinent men. DESIGN: Seventy-two healthy low-risk men (36 uncircumcised) and 25 HIV-positive men (12 uncircumcised) were enrolled in 3 double-blind, single-center studies as follows: 36 low-risk men in a study of BufferGel and K-Y Jelly (McNeil-PPC, Skillman, NJ) placebo; 36 low-risk men in a study of PRO 2000 Gel and vehicle placebo; and 25 HIV-positive men in a crossover study of BufferGel, PRO 2000 Gel, and K-Y Jelly placebo. METHODS: Participants applied product to the penis on 7 consecutive nights, kept study diaries, and were then interviewed and examined. Urine was tested for inflammation by leukocyte esterase. RESULTS: No serious adverse events (AEs) or urethral inflammation was detected. During use of BufferGel, 3 low-risk men (13%) reported 6 AEs and 2 HIV-positive men (8%) reported 3 AEs. During use of PRO 2000 Gel, 4 low-risk men (17%) reported 6 AEs and 1 HIV-positive participant (4%) had 1 AE. AE rates during use of BufferGel and PRO 2000 Gel use were not significantly different from rates observed during placebo. One low-risk man (4%) would object to his partners using BufferGel and 3 (13%) to PRO 2000 Gel. Two HIV-positive men (8%) reported they would object to partners using either BufferGel or PRO 2000 Gel. CONCLUSIONS: Daily application of BufferGel and PRO 2000 Gel directly to the penis consecutively for 7 days was generally safe and well tolerated among healthy low-risk men and HIV-positive men. These microbicides have acceptable safety profiles to proceed with planned phase 3 vaginal microbicide trials.

Evaluation of the efficacy of a nonlatex condom: results from a randomized, controlled clinical trial.

CONTEXT: To reduce unintended pregnancy and HIV infection, it is critical to develop reliable male condoms that will attract consumers who reject conventional latex condoms. METHODS: In a prospective clinical trial conducted in 1998-2000, 830 monogamous couples were randomized in equal numbers to use either a nonlatex condom or a commercial natural latex condom for six months as their only method of birth control. Couples completed detailed reports for the first five condom uses and recorded intercourse and condom use in coital diaries. Pregnancy rates associated with typical and consistent condom use were calculated using life-table analysis. Rates of clinical failure (condom breakage or slippage) were determined for the first five condom uses. RESULTS: During the first five uses, the nonlatex condom had a higher frequency of breakage or slippage during intercourse or withdrawal (4.0%) than latex condoms (1.3%); the breakage rate for the nonlatex condom was about eight times that of latex condoms. The six-cycle typical-use pregnancy rate did not differ significantly between users of nonlatex (10.8%) and latex condoms (6.4%). The six-cycle consistent-use pregnancy rate was higher for nonlatex condom users than for latex condom users (4.9% vs. 1.0%). CONCLUSIONS: The data present strong indirect support for public health messages that promote the use of latex condoms and, for individuals who cannot or are unwilling to use latex condoms, the use of nonlatex condoms for prevention of pregnancy and disease.

Use of prostate-specific antigen (PSA) to measure semen exposure resulting from male condom failures: implications for contraceptive efficacy and the prevention of sexually transmitted disease.

Accurate measurement of semen exposure resulting from condom failures can refine public health messages and improve predictions of condom efficacy in preventing pregnancy and HIV transmission. Eight hundred and thirty couples enrolled in a condom efficacy study were asked to collect a baseline sample of ejaculate from the inside of the first study condom they used and to collect a postcoital vaginal sample whenever a study condom broke or slipped off during intercourse. All samples were quantitatively tested for prostate-specific antigen (PSA), a substance found only in human semen, using rocket immunoelectrophoresis, and inspected microscopically for presence of sperm. Sixty-eight baseline ejaculate samples collected from the inside of the first study condom by couples who subsequently experienced a condom failure averaged 13.4 microg PSA per swab and 79% of the samples averaged one or more sperm per high power field (hpf). Seventy-nine postcoital vaginal samples obtained after a condom break averaged 5.7 microg PSA per swab and only 38% averaged one or more sperm per hpf. The PSA results indicated a 50% reduction in semen exposure compared to baseline levels (p = 0.0001). Seventeen samples obtained after a condom slip-off averaged 2.5 microg PSA per swab and none of the samples averaged one or more sperm per hpf. The PSA results indicated an 80% reduction in semen exposure compared to baseline levels (p = 0.0001). Our results suggest that even condoms that fail reduce the risk of pregnancy and the transmission of sexually transmitted disease compared to unprotected intercourse. We also used PSA results to adjust a model designed to predict consistent-use pregnancy rates from condom breakage and slippage data.