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Studies of condom use to reduce risk of most sexually transmitted infection provide inconsistent results. This inconsistency is often attributed to methodologic limitations yet has not been assessed systematically.The objectives of this study were to review studies of condom use and risk of gonorrhea and chlamydia, and to evaluate the importance of 4 key design and measurement factors on condom effectiveness estimates.We reviewed studies published 1966–2004 to assess risk reduction for gonorrhea and/or chlamydia associated with male condom use.Of 45 studies identified, most found reduced risk of infection associated with condom use. All studies reviewed had methodologic limitations: only 28 (62%) distinguished consistent from inconsistent use; 2 (4%) reported on correct use or use problems; 13 (29%) distinguished incident from prevalent infection; and one (2%) included a population with documented exposure to infection. Eight of 10 studies with 2 or more of these attributes reported statistically significant protective effects for condom use versus 15 of 35 studies with zero or one attribute (80% vs. 43%, P = 0.04).Condom use was associated with reduced risk of gonorrhea and chlamydia in men and women in most studies, despite methodologic limitations that likely underestimate condom effectiveness. Epidemiologic studies that better address these factors are needed to provide more accurate assessment of condom effectiveness.