Macaluso et al. Respond to "Condom Effectiveness and Prostate-specific Antigen"

Maurizio Macaluso1,, M. Louise Lawson2, Ann Duerr3 and Glen Hortin4

1 Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA.
2 Center for Pediatric Research, Eastern Virginia Medical School, Norfolk, VA.
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 Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.

Received for publication July 1, 2002; accepted for publication November 11, 2002.

Abbreviations: Abbreviation: PSA, prostate-specific antigen.

Steiner et al. (1) discuss our work (25) within the context of the debate on condom effectiveness (68). We agree that the available evidence indicates that condom use is highly effective against human immunodeficiency virus. Although the evidence is mixed regarding prevention of other sexually transmitted diseases, it does not (in our view) support the assertion that condom use is ineffective. Self-report of condom use may be exaggerated because of the social desirability of consistent use, and information bias may explain null studies (9). Furthermore, effectiveness can be evaluated only when an uninfected partner is exposed to an infected partner. Studies of couples serodiscordant for human immunodeficiency virus, in which every condom use may stop transmission, consistently show condom use to be effective. In contrast, in studies of sexually transmitted diseases such as gonorrhea and chlamydia, it is usually unknown whether (or when) a study participant is exposed to an infected partner during the study period. In these circumstances, condom-use effectiveness may be underestimated if condom use is more frequent with infected partners (10, 11).

For intercourse to lead to infection, biologic material must be transferred from the infected partner to the uninfected one: unprotected intercourse is an obvious exposure mechanism. When a condom is used, biologic material is unlikely to cross the intact condom sheath; however, breakage, slippage, and incorrect use may increase both the likelihood of exposure and its intensity (i.e., the quantity of material transferred). The true frequency of such events is difficult to determine, and we have little evidence on their effect on exposure. In the procedures we developed for our studies, detection of prostate-specific antigen (PSA) provides objective evidence of semen transfer during intercourse (4, 5). The method can partially validate self-report. For example, a high PSA level would contradict self-reported abstinence during the previous 24–48 hours. In the present study, we used PSA to corroborate self-reported female condom failure and to assess the extent of exposure during female condom use. We evaluated exposure only when a condom was used and inspected the returned condoms (2, 3). Thus, we are confident that condom nonuse cannot explain the exposures detected in the study (although unreported incorrect use could).

Steiner et al. (1) are concerned by the high exposure frequency we observed and question its validity because they perceive the boundaries of the semen exposure rate to be arbitrary and believe some PSA results may have been due to sample contamination. We cannot directly address the hypothesis that contamination (i.e., contact of the sampling device with semen outside of the vaginal cavity) may explain the exposures detected, but the design of the device and procedures, together with the rarity of self-reported problems during sampling, lead us to believe this explanation unlikely (2). We chose quantitative criteria to specify the boundaries of a "semen exposure rate" to simplify presentation of what seems to be a distribution of exposure levels of varying intensity rather than a dichotomous exposure that should yield a PSA value below or above a threshold.

In controlled conditions, PSA levels are a function of exposure intensity (4). The distribution of PSA levels in samples collected 1 hour after intravaginal exposure to 10, 100, and 1,000 µl of semen (figure 1) should help in interpreting the PSA levels observed after female condom use (refer to figure 2 in the paper by Macaluso et al. (2)) and suggests that the vast majority of the exposures we observed derive from the transfer of minute quantities of semen. Thus, our findings suggest that when a female condom is used, small quantities of biologic material may be transferred during intercourse, that such low exposure is common, and that high levels of exposure are rare. Elevations in PSA levels track self-reported events commonly interpreted as condom failure, suggesting that when a condom breaks or slips completely, it may lead to high exposure, resulting in a proportionately higher PSA signal and possibly a higher risk for adverse outcomes (2). The association of PSA levels with characteristics of the partners and of the intercourse indirectly corroborates the hypothesis that the distribution of PSA values reflects true exposure rather than error (3).



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FIGURE 1. Percentage distribution of prostate-specific antigen (PSA) values (ng/ml) in 222 samples of vaginal fluid self-collected by 40 women 1 hour after exposure to 0.01 ml (n = 80), 0.1 ml (n = 76), and 1 ml (n = 66) of their partner’s semen, Birmingham, Alabama, 1997–1998. Each woman was asked to collect two samples (18 samples were not returned).

 
In closing, we agree with Steiner et al. (1) that our conclusions must be tentative, both because our study (2, 3) is probably a first and because it evaluated only the female condom. More work is needed to further clarify the quantitative relation among semen exposure levels, PSA values, and the risk for specific biologic outcomes. We are confident that future advances in our understanding and application of this technology will help improve the validity of studies evaluating the effectiveness of condom use and strengthen the evidence upon which public health policies should be based.


    NOTES
 
Correspondence to Dr. Maurizio Macaluso, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Centers for Disease Control and Prevention, 4770 Buford Highway, Mail Stop K-34, Atlanta, GA 30341-3724 (e-mail: mmacaluso{at}cdc.gov). Back


    REFERENCES
 TOP
 REFERENCES
 

  1. Steiner MJ, Feldblum PJ, Padian N. Invited commentary: condom effectiveness—will prostate-specific antigen shed new light on this perplexing problem? Am J Epidemiol 2003;157:298–300.[Free Full Text]
  2. Macaluso M, Lawson ML, Hortin G, et al. Efficacy of the female condom as a barrier to semen during intercourse. Am J Epidemiol 2003;157:289–97.[Abstract/Free Full Text]
  3. Lawson ML, Macaluso M, Duerr A, et al. Partner characteristics, intensity of the intercourse, and semen exposure during use of the female condom. Am J Epidemiol 2003;157:282–8.[Abstract/Free Full Text]
  4. Lawson L, Macaluso M, Bloom A, et al. Objective markers of condom failure. Sex Transm Dis 1998;25:427–32.[ISI][Medline]
  5. Macaluso M, Lawson L, Akers R, et al. Prostate-specific antigen in vaginal fluid as a biologic marker of condom failure. Contraception 1999;59:195–201.[CrossRef][ISI][Medline]
  6. National Institute of Allergy and Infectious Diseases. Workshop summary: scientific evidence on condom effectiveness for sexually transmitted disease (STD) prevention, July 20, 2001. (http://www.niaid.nih.gov/dmid/stds/condomreport.pdf).
  7. Cates W. The NIH condom report: the glass is 90% full. Fam Plann Perspect 2001;33:231–3.
  8. Fitch JT, McIllhaney JS, Adam MB, et al. Sex, condoms and STDs: what we now know. Austin, TX: The Medical Institute, 2002.
  9. Zenilman JM, Weisman CS, Rompalo AM, et al. Condom use to prevent incident STDs: the validity of self-reported condom use. Sex Transm Dis 1995;22:15–21.[ISI][Medline]
  10. Warner L, Newman D, Peterman TA, et al. Minimizing differences in exposure to infection in condom effectiveness studies for STD prevention. (Abstract). Am J Epidemiol 2002;155:S40.[CrossRef]
  11. Peterman TA, Lin LS, Newman DR, et al. Does measured behavior reflect STD risk? An analysis of data from a randomized controlled behavioral intervention study. Project RESPECT Study Group. Sex Transm Dis 2000;27:446–51.[ISI][Medline]

Related articles in Am. J. Epidemiol.:

Efficacy of the Female Condom as a Barrier to Semen During Intercourse
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Am. J. Epidemiol. 2003 157: 289-297. [Abstract] [FREE Full Text]  

Invited Commentary: Condom Effectiveness—Will Prostate-specific Antigen Shed New Light on This Perplexing Problem?
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Am. J. Epidemiol. 2003 157: 298-300. [Extract] [FREE Full Text]  

Partner Characteristics, Intensity of the Intercourse, and Semen Exposure During Use of the Female Condom
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