A phase I comparative study of contraceptive vaginal films containing benzalkonium chloride and nonoxynol-9: Postcoital testing and colposcopy

Abstract

Benzalkonium chloride (BZK) has been shown in in vitro and in vivo studies to immobilize sperm, to be active against STD-causing organisms, and to penetrate and thicken cervical mucus. A US clinical study of a sponge containing 60 mg BZK showed life table pregnancy rates at 6 and 12 months of 11.7 and 18.9 per 100 women, respectively. BZK is not currently marketed in the US as a contraceptive. The present study aimed to assess 1) the ability of a new contraceptive vaginal film containing either of two doses of BZK to prevent the penetration of sperm into midcycle cervical mucus; 2) the effect of the film on the vaginal epithelium; and 3) the acceptability of the film. All results were compared with VCF ®, a currently marketed film containing nonoxynol-9 (N-9). Ten women underwent two baseline cycles of postcoital testing in which no film was used, followed by three test cycles in which Allendale-BZK film, a new film containing either 19 or 25 mg BZK, or VCF, containing 70 mg N-9, was used. The sequence of testing cycles was randomized. In each cycle, condoms were used prior to midcycle, then a midcycle cervical mucus specimen was examined to ensure midcycle characteristics and the absence of sperm. Each woman then had intercourse using either no film (baseline cycles) or a test film (test cycles) and returned 2–3 h afterwards. Cervical mucus was again assessed for adequacy and the presence of sperm. Each woman also underwent colposcopy, using a protocol developed by the World Health Organization. The average number of progressively motile sperm seen per high power field was as follows: first baseline cycle, 22.2; second baseline cycle, 22.1; test cycle with film containing 19 mg BZK, 0.2; test cycle with film containing 25 mg BZK, 0.0; and test cycle with VCF containing 70 mg N-9, 0.0. There was no significant difference between baseline cycles or among test cycles in the average number of progressively motile sperm seen (p = 0.78 and p ≥ 0.75, respectively). The average number of progressively motile sperm seen in each test cycle did, however, differ significantly from the average number seen in either baseline cycle (p < 0.01). Colposcopy showed superficial de-epithelialization without underlying inflammation in 15–20% of baseline cycles, regardless of whether colposcopy was done before or after coitus; in 50% of cycles in which either dose of BZK was used; and in 69% of cycles in which VCF was used. In all cases women were asymptomatic. Erythema and petechiae were also seen on colposcopy although at a lower frequency than de-epithelialization. There was no difference in the acceptability of the films. A vaginal contraceptive containing either 19 or 25 mg BZK in a new film base appears to be comparable with VCF in preventing sperm from entering midcycle cervical mucus and may be somewhat less disruptive to the vaginal epithelium.