Efficacy and safety of doxycycline versus azithromycin for the treatment of Chlamydia trachomatis in cis-men: A systematic review and meta-analysis

Introduction Treatment for Chlamydia trachomatis include azithromycin and doxycycline; however, comparative studies in cis-male populations remain limited. This systematic review and meta-analysis assessed the efficacy and safety of azithromycin versus doxycycline for treating chlamydial infections among cis-men. Methods We searched PubMed/MEDLINE, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar. Randomized controlled trials comparing doxycycline (100 mg twice daily for 7 days) with azithromycin (1 g single dose) in cis-men infected with Chlamydia trachomatis were included. Risk of bias was assessed using the Cochrane RoB 2 tool and meta-analysis was reported in accordance with the PRISMA 2020 guidelines. The primary outcome was microbiological cure at last follow-up. Pooled effect estimates were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using the random-effects model. Subgroup, meta-regression, publication bias and sensitivity analyses were performed. The protocol was registered in PROSPERO (CRD42024535957). Results 10 randomized controlled trials comprising 1172 cis-male participants were included. Overall, 560/602 (93%) participants treated with doxycycline and 504/627 (81%) treated with azithromycin achieved microbiological cure. Meta-analysis demonstrated significantly higher odds of cure with doxycycline compared with azithromycin (OR = 2.525, 95% CI = 1.329–4.796, p = 0.005). Adverse events were not significantly different between groups ( p = 0.757). Subgroup analysis showed significant superiority of doxycycline for rectal infection and chlamydia-associated nongonococcal urethritis ( p < 0.05), but not for prostate infection ( p = 0.745). Sensitivity analysis demonstrated strong reliability and no statistical evidence of publication bias ( p > 0.05). Conclusions Doxycycline demonstrated superior microbiological efficacy compared with azithromycin in cis-men with Chlamydia trachomatis . However, moderate heterogeneity was detected across studies and data for rectal and prostate infections were limited. Consequently, further well-designed trials are required to confirm these findings.